Abstract: Objective To clarify the efficacy and potential mechanism of Cordyceps militaris extract to nourish kidney yang. Methods SD rats were divided into normal, model, testicular tablet (0. 216 g / kg), and Cordyceps militaris extract high, medium, and low dose groups (0. 72, 0. 36 and 0. 18 g / kg, respectively) with 10 per group. Except for the normal group, all other groups were administered adenine (200 mg / kg) by gavage to establish a kidney yang deficiency rat model. Test drug administration was started on day 15 of model establishment for 28 consecutive days. ELISA were used to measure rat serum gonadotropin releasing hormone (GnRH), luteinizing hormone (LH), testosterone (T) and estradiol (E2) levels. HE staining was used to observe the morphology of kidneys, testes, epididymis, and seminal vesicle glands. Immunohistochemistry and Western blot were used to detect CYP19, CaM and CaMKⅡ expression in testes. CYP19 mRNA expression was detected in testes by RT-qPCR. Results Compared with the normal group, serum GnRH, LH and T levels of the model group were significantly reduced (P<0. 05), kidney, testis, epididymis and seminal vesicle gland tissues were all significantly damaged, and CYP19 expression in testes was reduced (P<0. 01). CaMKⅡ expression was increased significantly (P<0. 01). CYP19 mRNA expression was decreased significantly (P<0. 01). Compared with the model group, GnRH, LH and T contents in the high-dose Cordyceps militaris extract group were increased (P< 0. 05), tissue damage was relieved, CYP19 expression in testis was increased (P<0. 05), CaM and CaMKⅡ were decreased (P< 0. 05), and the CYP19 mRNA level was increased (P<0. 05). Conclusions Cordyceps militaris extract exerts a kidney yang effect by regulating CYP19 / CaM/ CaMKⅡ signaling.

Abstract: Objective To explore the mechanism of triptolide reducing oxygen glucose deprivation / reoxygenation (OGD/ R)-induced SH-SY5Y cell injury via the NogoA/ RhoA/ ROCK signaling pathway. Methods The effect of various triptolide concentrations on SH-SY5Y cell proliferation was assessed by CCK8 assays to select the optimal concentration. Cells were divided into normal control, model, triptolide (1 nmol / L) treatment and fasudil (15 μg / mL) treatment groups. Cell proliferation was assessed by CCK8 assays. A JC-1 assay was used to measure the mitochondrial membrane potential. NogoA, ROCK2 and GAP43 expression was detected by immunofluorescence staining. GAP43, PSD95, NogoA, NgR, RhoA and ROCK2 expression was detected by Western blot. Results CCK8 assays showed that the optimal concentration of triptolide was 1 nmol / L. Cell proliferation and the mitochondrial membrane potential of the model group were significantly lower than those of the control group ( P< 0. 001). Compared with the control group, GAP43 and PSD95 expression was decreased and NogoA, NgR, RhoA and ROCK2 expression was increased in the model group (P<0. 001). Both triptolide and fasudil increased cell proliferation (P<0. 001) the and mitochondrial membrane potential (P<0. 001), upregulated GAP43 and PSD95 expression (P<0. 05), and downregulated NogoA, NgR, RhoA and ROCK2 expression (P<0. 001). Conclusions Triptolide may alleviate OGD/ R-induced SH-SY5Y cell injury by inhibiting the NogoA/ RhoA/ ROCK signaling pathway.

Abstract: Objective Proteomics were used to analyze changes in the liver protein expression profile of AFLD mice and the effect of resveratrol treatment. Methods The AFLD model of C57BL/ 6J mice was prepared by NIAAA method, and resveratol(400 mg / kg)was administered orally for 9 days. Proteins in the liver tissues were quantified by the 4D non-standard quantitative proteomic method . Under conditions of multiple changes ≥1. 5 or ≤0. 67 and P< 0. 05, significantly up- or down-regulated differentially expressed proteins in three comparison groups were screened. GO classification, KEGG pathway enrichment, and protein network interaction analysis of differentially expressed proteins were carried out. Results Totals of 4513 and 3763 proteins were identified and quantified, respectively, and 1228 differentially expressed proteins and 11 differentially coexpressed proteins were screened. Compared with the control group (P<0. 05), 370 and 324 proteins were significantly down- and up-regulated in the AFLD group. Compared with the AFLD group (P< 0.05), 224 and 227 proteins were significantly up- and down-regulated, respectively, in the resveratrol treatment group. A total of 1228 differentially expressed proteins were involved in 40 biological processes, 36 cellular components, 38 molecular functions, and 45 KEGG pathways annotated by GO classification. A total of 11 differentially coexpressed proteins were screened and found to be related to 9 molecular functions and 5 signaling pathways, of which 4 differentially coexpressed proteins interacted. Conclusions After chronic alcohol intake, the protein expression profile of mouse liver tissue changes significantly. The changes in expression of Sult1b1 (sulfotransferase family cytosolic 1B member 1), Apoa4 (apolipoprotein A-IV), Gpat3 ( glycerol-3-phosphate acyltransferase 3), and Ephx1 ( epoxide hydrolase 1) were closely related to AFLD occurrence and the therapeutic effect of resveratrol on AFLD.

Abstract: Objective To explore a safe, stable and repeatable model of gouty arthritis (GA) with damp-heat syndrome by comparing changes in lipid metabolism and proinflammatory factors between two rat models of GA with damp- heat. Methods Overall, 44 male SD rats were randomly divided into a control group ( n= 10), GA group ( n= 10), model group A (n= 12) and model group B (n= 12). The specific method was provided in full text, and the experimental period lasted for 21 days. The general condition of rats in each group was observed during the modeling period and the mortality rate was assessed after modeling. Ankle swelling was measured by the circumference method . Serum contents of lipid metabolism factors (TG, TC, LDL-C and HDL-C) and proinflammatory factors (NF-κB, IL-1β, TNF-α and IL-6) were determined by ELISA. Results The mortality rate was 8. 3% (1 / 12) in model group A and 25% (3 / 12) in model group B. Compared with control and GA groups, the serum TG, TC, and LDL-C were significantly higher in the model group A and B (P<0. 01), while HDL-C was decreased significantly (P<0. 01). Compared with model group A, TG and HDL-C were increased in the model group B, while TC and LDL-C were decreased, but without statistical significance (P>0. 05). Compared with the control group, serum NF-κB, IL-1β, IL-6 and TNF-α were significantly higher in the GA group, and model group A and B (P<0. 01). Compared with the GA group, NF-κB and TNF-α were increased in the model group A (P<0. 05), and NF-κB, IL-1β, IL-6 and TNF-α were increased in model group B (P<0. 05). Compared with model group A, IL-1β, IL-6 and TNF-α were increased in model group B ( P< 0. 05 ). Conclusions Both approaches successfully induced a combined model of GA with damp-heat syndrome. Both of them had commonalities and individualities. The high fat and sugar diet was a directly influencing factor for lipid metabolism disorder. Biological factors had more obvious effects on inflammation in rats than a high temperature and humidity environment.

Abstract: Objective To compare and analyze differences between two modeling method of mouse pre-eclampsia (PE), and to provide a reference to select different types of PE animal models. Methods Overall, 24 CD-1 pregnant mice were randomly divided into LPS control, LPS, R848 control and R848 groups with six mice in each group. Saline or LPS (4 mg / kg) was injected intravenously via the tail vein into mice in LPS control or LPS groups on days 13 ~ 17 of pregnancy. R848 solvent or R848 (10 mg / kg) was injected intraperitoneally into mice of R848 control and R848 groups on days 13, 15 and 17 of pregnancy. Systolic blood pressure of the tail artery was measured on days 12, 14, 16 and 18 of pregnancy. The mice were dissected on day 18 of pregnancy, followed by urine protein / creatinine detection, anti-vascular generation factor detection, and HE staining. Results Compared with the control group, gestational hypertension occurred in both modeling method. Blood pressure on days 14, 16 and 18 of pregnancy in the LPS group was ( 142. 16±4. 81), (144. 07±2. 91), and (143. 31±4. 61) mmHg, respectively. Blood pressure on days 14, 16 and 18 of pregnancy in the R848 group was ( 154. 00 ± 5. 29), ( 147. 44 ± 3. 24) and ( 140. 77 ± 2. 00) mmHg, respectively. Urine protein / urine creatinine tests showed that the ratio was increased in the LPS model group ( P< 0. 05), but there was no statistical difference in the R848 group ( P> 0. 05). Compared with the corresponding control group, there was no significant difference in sFlt-1 or sEng expression in the lipopolysaccharide group (P>0. 05), whereas sFlt-1 and sEng expression was increased in the R848 group (P<0. 01). Compared with the control group, the R848 group had chronic injury of placental blood vessels, and extensive hyperplasia of syncytiotrophoblasts in pregnant mice. Conclusions Both modeling method induce symptoms of PE in pregnant mice, such as hypertension, fetal growth restriction, and endothelial dysfunction. However, the damage caused by the R848 modeling method is more serious and its advantage is a simple operation.

Abstract: Objective To investigate the effects of mitochondrial ferritin (FtMt) on epithelial mesenchymal transition (EMT) of-cisplatin-resistant non-small lung cancer line A549 / DDP and non-small lung cancer line A549, and to explore the molecular mechanism in improving cisplatin resistance. Methods Flow cytometry was used to determine the apoptosis rate and cell cycle of A549 and A549 / DDP cells. Western blot was used to analyze expression of E-cadherin, N- cadherin and FtMt. RT-qPCR was used to measure gene expression of E-cadherin, N-cadherin, snail, slug, twist, vimentin, FPn, DMT1, hepcidin and TfR1 in cells. Cell migration was assessed by a scratch assay. Results The apoptotic rate of A549 / DDP and A549 cells was increased with the increase in cisplatin concentration, and the apoptotic rate of A549 cells was significantly higher than that of A549 / DDP cells. After cisplatin treatment, A549 cells in G0 / G1 and G2 / M phases were gradually decreased in all groups compared with the 0 μg / mL cisplatin group, whereas A549 / DDP cells in G0 / G1 and G2 / M phases were first increased and then decreased (P<0. 05). The protein and mRNA levels of E-cadherin in A549 / DDP cells were lower than those in A549 cells, while the protein and mRNA levels of N-cadherin in A549 / DDP cells were higher than those in A549 cells. The mRNA levels of snail, slug, vimentin, FPn, hepcidin and TfR1 in A549 / DDP cells were higher than those in A549 cells (P<0. 05). The mRNA level of DMT1 in A549 / DDP cells was lower than that in A549 cells (P>0. 05). The cell migration rate was significantly faster in A549 / DDP cells than in A549 cells (P<0. 05). The expression of FtMt in A549 / DDP cells was significantly higher than that in A549 cells (P< 0. 05). Conclusions Cisplatin resistance of lung cancer cells is related to the EMT process, and FtMt might play an important role in cisplatin resistance of lung cancer cells.

Abstract: Objective To explore the association and role of autophagy in vascular calcification of chronic kidney disease. Methods Overall, 30 SD rats were randomly divided into a control group (Control group, n= 15) and adenine and high phosphorus diet-induced model group (CKD group, n= 15). Immunohistochemistry was applied to detect α-SMA, RUNX2, LC3B and Beclin-1 in the aorta. Calcium content was measured to further analyze the correlation between them. Aorta smooth muscle cell (ASMC) calcification was induced by β-GP. Autophagy activation was detected by electron microscopy, immunofluorescence, and Western blot. After 3-MA and RAP regulation of autophagy, immunohistochemistry and Western blot were used to detect α-SMA and RUNX2 protein expression, and alizarin red staining and calcium contents were used to detect calcification of ASMC. Results Compared with the control group, vascular calcification was established in the CKD group. RUNX2, LC3B and Beclin-1 proteins, and calcium content were higher in the CKD group than in the control group, while α-SMA protein expression had declined. Correlation analysis showed that Beclin-1 and LC3B protein expression were positively correlated with aortic calcium content and RUNX2 protein expression, respectively. β-GP induced ASMC calcium deposition and osteogenic differentiation. β-GP induced an increase of autophagosomes, LC3B fluorescent spots, and LC3BII protein expression (P<0. 01). After autophagy activation by RAP, calcium deposition and content (P<0. 05) and RUNX2 protein expression (P< 0. 05) were reduced, while α-SMA protein expression was promoted (P<0. 05). After-autophagy inhibition by 3-MA, calcium deposition and content were increased (P< 0. 05), RUNX2 protein expression was promoted ( P< 0. 05 ), and α-SMA protein expression was decreased ( P< 0. 05 ). Conclusions Autophagy might play a protective role in CKD vascular calcification. Autophagy is expected to become a new therapeutic target for CKD vascular calcification.

Abstract: Objective To investigate the effect of xenoestrogen nonylphenol (NP) on the proliferation, invasion, and migration of colorectal cancer cells and its relationship with sulfiredoxin-1 ( SRXN1 ) expression. Methods Transcriptomic sequencing and qRT-PCR were used to analyze the effect of NP, SRXN1 expression in colorectal cancer cells. SRXN1 expression in colorectal cancer was analyzed by TCGA and immunohistochemistry. After SRXN1 knockdown in colorectal cancer cell line COLO205 by a specific small interfering RNA ( si-SRXN1 ), effects on the activity, proliferation, ROS release, invasion, and migration of NP (10^-6 mol / L)-treated COLO205 cells was detected by CCK-8, colony formation, transwell, and invasion assays. ERK1 / 2, PI3K/ Akt and Wnt / β-catenin expression was assessed by Western blot. Results Transcriptome sequencing and qRT-PCR analysis showed that NP significantly upregulated SRXN1 expression in COLO205 cells. TCGA and IHC analysis showed that SRXN1 expression in colorectal cancer tissue samples was significantly higher than that in the paracancerous group (P<0. 01). Compared with control group, NP significantly promoted COLO205 cell viability, colony formation, invasion, and migration (P<0. 01). si-SRXN1 significantly inhibited cell proliferation, invasion, and migration (P< 0. 01). Compared with the si-SRXN1 group, cell viability ( P< 0. 01), colony formation (P<0. 05), invasion (P<0. 01), and migration (P<0. 01) were significantly increased in the NP+si- SRXN1 group. Western blotting showed that, compared with the control group, ERK1 / 2, PI3K/ Akt, and Wnt / β-catenin were significantly increased in the NP group ( all P<0. 01) and significantly decreased in the si-SRXN1 group ( all P< 0. 01). Compared with the si-SRXN1 group, ERK1 / 2, PI3K/ Akt and Wnt / β-catenin were significantly increased the in NP+si-SRXN1 group (P<0. 05 or P<0. 01). Conclusions NP promotes the proliferation, invasion, and metastasis of colorectal cancer cells by promoting SRXN1 expression.

Abstract: Objective To determine the current pathogenic microbiology quality status of experimental rats and mice in Shaanxi province, we analyzed quality monitoring result from 2017 to 2021 to provide a reference for health screening of laboratory rats and mice. Methods Using the current national standards GB 14922. 2-2011, GB/ T 14926- 2001, and GB/ T 14926. 21-2008, the Laboratory Animal Quality Supervision and Testing Center of Shaanxi carried out pathogenic microbial and parasite quality sampling tests on SPF rats and mice in all licensed companies and research institutes, and then analyzed the result. Results From 2017 to 2021, 2549 SPF mice and 503 SPF rats were collected from 109 and 45 organizations, respectively. Mouse parasite detection showed a reduction of mites from 5. 26% to 0. 15%, intestinal flagellates from 10. 53% to 0. 45%, Salmonella and Tyzzer’s organism from 2. 78% and 1. 38%, respectively, to undetected. Intestinal helminths increased from 0. 40% to 2. 39%. In rats, there were declines in mites and Staphylococcus aureus from 7. 07% and 1. 77%, respectively, to undetected, intestinal flagellates from 11. 50% to 0. 83%, and enrichment of helminths from 3. 79% to 7. 50%. In terms of positive rates of mouse serum antibodies, in 2017, mouse hepatitis virus ( 4. 71%), Sendai virus ( 1. 39%), and minute virus of mice ( 2. 22%) were positive. Additionally, in 2021, mouse hepatitis virus (0. 30%) and Sendai virus (0. 15%) were positive. These result indicated raised trends of both pneumonia virus of mice and reovirus type III. However, there was a reduction in Sendai virus from 7. 07% to 0. 83% and an increase of pneumonia virus from 0. 88% to 10. 00%. In rats, although parvovirus and coronavirus had predominant potentials, which were detected in the past 5 years, the number of infected organizations and the positive rate showed a downward trend annually. Conclusions The test result in the past 5 years showed that pathogenic microorganisms in rats and mice in Shaanxi province had improved yearly. However, many problems still existed. Therefore, strict biosafety prevention and control measures should be conducted continuously, and the animal experimentation process should be strengthened to ensure that animals are qualified within the experimental period.

Abstract: Objective To determine localization of the rat thyroid gland by ultrasound technology, analyze and evaluate lesions and the degree of modeling in the rat nodular goiter model, and provide a technical method for diagnostic evaluation of the rat model of nodular goiter and related thyroid diseases. Methods Forty 6 ~ 8 weeks old SPF-grade Wistar rats (male and female) were used as the control group and 20 rats were instilled with a propylthiouracil (PTU) solution for 8 weeks to establish a rat model of nodular goiter. Ultrasound examination of the thyroid gland was performed after modeling, along with pathological examination for comparison with ultrasound. Results Ultrasonography showed that the anterior-posterior and medial-lateral diameters of the thyroid gland in the model group were significantly larger than those in the control group (P<0. 001). Conversely, asymmetric enlargement of the gland was observed in the model group. The shape and size of thyroid tissue and the follicle size were irregular in HE-stained thyroid glands of the model group. In the group, epithelial cells were obviously hyperplastic, disorganized and unevenly distributed with compressed colloid. Ultrasound and pathological tests were consistent with the disease diagnosis. Conclusions Ultrasound is a good method for in vivo evaluation of a rat nodular goiter model.

Abstract: Objective To study the effect of macrophage-specific knockout of AMP-activated protein kinase α1 (AMPKα1) on a high fat, fructose and cholesterol diet-induced non-alcoholic fatty liver disease (NAFLD) mouse model and to explore the possible mechanism. Methods Lyz2-cre mice ( macrophage-specific cre mice) and AMPKα1^{flox / flox} (AMPK^{fl/ fl} ) mice were crossed to generate macrophage-specific AMPKα1 gene knockout ( AMPKΔMφ ) mice by DNA genotyping. AMPKα1^{flox / flox} mice and APMKΔMφ mice were fed a high fat, fructose, and cholesterol diet (CHFF diet)for 12 weeks to establish the NAFLD model. Glucose tolerance was measured by an OGTT. Differences in liver pathological changes of the two kinds of mice were observed by HE staining. Accumulation of liver lipid droplets was observed by oil red O staining. Changes in serum lipomics of two kinds of mice were assessed by GC-MS. Results Genotyping by gel electrophoresis showed that the AMPKα1^{flox / flox} band was 450 bp, the corresponding wildtype band was 334 bp, the lyz2-cre band was 700 bp, and the corresponding wildtype band was 350 bp. Western blot confirmed that macrophages of AMPK^△Mφ mice did not express AMPKα. AMPKα expression was found in macrophages of AMPK^{fl/ fl} control mice. In the NAFLD model, compared with AMPK^{fl/ fl} mice, more hepatocytes in AMPK^△Mφ mice showed steatosis and an increase in the oil red O staining area. OGTT showed that, compared with AMPK^{fl/ fl} mice, blood glucose of AMPK^△Mφ mice was increased significantly at 15 min. Non-targeted lipomics showed that the serum levels of propionic and lactic acids in AMPK^△Mφ mice were significantly lower than those in AMPK^{fl/ fl} mice. Conclusions Macrophage-specific AMPKα1 knockout promotes hepatic steatosis and downregulates serum propionic acid and lactate levels in NAFLD model mice.

Abstract: Objective To analyze the strain selection, sex, modeling key points, evaluation method of 6- hydroxydopamine(6-OHDA) induced Parkinson’ s disease ( PD) model in rats and its application on the screening of traditional Chinese medicine in the treatment of Parkinson’ s disease. Methods Recent literatures related to 6-OHDA models in the CNKI and PubMed databases in 20 years were collected. The strains of rats, the weight, sex, modeling key points, evaluation method were analyzed, along with the application of 6-OHDA model in anti-PD traditional Chinese medicine screening. Results Male SD or Wistar rats are mostly selected as PD models in rats induced by 6-OHDA. The injection site is usually unilateral substantia nigra, medial forebrain bundle or striatum. Apomorphine induced rotation experiment, brain histomorphology, molecular biology and biochemical indicators are usually detected 4 weeks after modeling to determine the success rate of the model and the effectiveness of drugs for prevention and treatment of PD. Conclusions This study provides a useful reference for the use of 6-OHDA induced PD model regarding the strain selection, sex, modeling key points, evaluation method and the application on the screening of traditional Chinese medicine in the treatment of PD.

Abstract:Ischemic stroke is a common type of cerebrovascular disease and often leads to death or disability in the global aging population. Tight junction integrity is closely related to ischemic stroke. Excessive destruction of tight junctions and increased permeability of the blood-brain barrier after brain tissue ischemia aggravates the pathological progression of ischemic brain injury. A large number of studies have shown that traditional Chinese medicine can effectively repair the tight junctions between cerebral vascular endothelial cells after ischemic stroke, thereby reducing damage to the blood-brain barrier and promoting recovery after brain injury. This review elucidates the possible mechanisms of the active components of traditional Chinese medicine, including monomers and monomers their extracts, and other compounds, in improving the neurological damage of ischemic stroke by regulating tight junctions. Progress in the discovery of clinical uses of traditional Chinese medicine for ischemic stroke are reviewed, including the new target of cerebral apoplexy.

Abstract:Fucosylation is one of the most common glycosylation modifications that is closely related to the occurrence, development, and prognosis of cancer. A change in fucosyltransferase correlations with tumor multidrug resistance has been reported. Multidrug resistance of tumor cells is a major factor affecting chemotherapy efficacy, which often leads to a poor therapeutic effect and prognosis. This review focuses on the relationship between fucosyltransferase family members and their catalytic fucosylation modification and tumor multidrug resistance, briefly summarizes the therapeutic effect of fucosylation inhibitors on tumors, and describes fucosylation analogues as fucosylation inhibitors that may be potential drugs to reverse tumor multidrug resistance. This article provides a basis for fucosylation modification as a drug target to reverse and sensitize tumor drug resistance.

Abstract:Glutamate is the main excitatory neurotransmitter in the central nervous system. Under physiological conditions, glutamate plays an important role in signal transduction. Under pathological conditions, abnormal accumulation of extracellular glutamate can easily cause a series of excitotoxic injuries such as cytoxic edema, degeneration and death of neurons, leading to various nervous system diseases such as Parkinson’ s disease, Alzheimer’ s disease, epilepsy, retinal damage, and hearing loss. Glutamate-aspartate transporter (GLAST) is one of the main excitatory glutamate transporters that maintains the concentration of glutamate at the optimal extracellular level, which prevents glutamate from accumulating in the synaptic space to produce excitotoxicity. This review clarifies the research progress of GLAST in nervous system diseases to understand GLAST-related mechanisms.

Abstract:N-methyl-D-aspartate (NMDA) receptor plays an important role in the function of the nervous system. The NR2B subunit is the regulatory subunit of NMDA receptor, which is closely related to the neuroprotection of hypoxia / ischemia. Phosphorylation of NR2B is considered to be an important mechanism to regulate the NMDA receptor function and plays an important role in ischemic / hypoxic neuroprotection through the change in phosphorylation. This review discusses the development of the NR2B subunit of NMDA receptor and the relationships between the structure, function, phosphorylation, signaling pathway and ischemic / hypoxic neuroprotection to provide a theoretical foundation to prevent and treat hypoxic / ischemic brain diseases with NR2B subunit as the target.

Abstract:Allergic asthma is a chronic airway inflammatory disease caused by type 2 inflammatory response- mediated hypersensitivity. At present, no animal model of asthma that completely recapitulates the occurrence and development of allergic asthma in humans is available. Therefore, it is particularly important to establish a relatively complete and stable animal model of allergic asthma that conforms to the pathological manifestations of patients. This review briefly analyzes the strain selection, modeling method, and model evaluation indicators of allergic asthma model rats in the past 5 years.

Abstract:Hemorrhagic shock (HS) is one of the common causes of death, which is mostly due to trauma- induced fracture of limbs and rupture of vital organs, aneurysm rupture, and other causes of massive bleeding. The causes, triggers, and mechanisms of HS and establishment of animal models have been largely clarified, but animal models of HS combined with or complicated by other diseases need to be investigated further. Thus, we reviewed the current research status of the selection and application of various animals for HS models and their combination or complication with other disease models to provide researchers with a reference for the selection and application of HS-related models.

Abstract:As a newly discovered ICI, Siglec-15 is widely expressed in various tumor cell types, and PD-1/ PD-L1 expressions is mutually exclusive. Siglec-15 may be a new therapeutic target for PD-1/ PD-L1 as a treatment option for patients who do not respond to therapy. This review discusses the recent research of the characteristic pathways of Siglec- 15, its involvement in immune regulation mechanisms, and its tumor-related expression. Clinical application of an anti- Siglec-15 antibody was analyzed, and the therapeutic prospect of Siglec-15 for NSCLC treatment is discussed.