Cancer immunotherapy has emerged as a promising strategy. However, low response rates and immune-related side effects have plagued immunotherapy. Metallic nanoparticles, utilizing metals as their framework, are gaining prominence in cancer immunotherapy. Metal ions have shown the ability to modulate immune status by activating the cGAS-STING pathway and inducing immunogenic cell death (ICD), thereby enabling multidimensional activation of immunotherapy. Metallic nanoparticles offer significant advantages in cancer immunotherapy, leading to their increasing use in enhancing therapeutic outcomes. In view of the ever-increasing research on metallic nanoparticles, this review presents the construction, characterization, and enhanced cancer immunotherapeutic effects of different types of metal nanosystems from the perspective of the immunoregulatory mechanisms of metal ions. We delve into the current limitations and future directions of metallic nanoparticles in this rapidly evolving field. To the best of our knowledge, this review offers the most up-to-date and systematic analysis of metallic nanoparticles in immunotherapeutic applications. It is anticipated that this review of metallic nanoparticles will inspire a more refined and intelligent design of metallic nanoparticles for future research, paving the way for advancing their clinical applications.

Gastroesophageal reflux disease （GERD） is a frequently and commonly occurring disease in clinic. In recent decades， with the development in pathophysiology and drug researches， modern medicine has achieved remarkable progress and results in diagnosis and treatment. However， the treatments for non-erosive reflux disease， refractory gastroesophageal reflux disease， proton pump inhibitor resistance， overlap of disease symptoms， and extraesophageal symptoms are limited and ineffective. Traditional Chinese medicine （TCM） was widely used in clinical practice， which has been proved effective in relieving symptoms and improving the quality of life. Sponsored by China Association of Chinese Medicine （CACM） and undertaken by the Spleen and Stomach Disease Branch of CACM， "the 12^th Youth Salon of Clinical Predominance Disease Series （GERD）" invited 18 authoritative digestive experts of TCM and western medicine to discuss "the difficulties of clinical diagnosis and treatment of GERD and TCM advantages". The focus issues such as modern medical diagnosis and treatment achievements and contributions， improvement and maintenance of symptoms， response to overlapping disease symptoms， reduction and withdrawal of acid suppressors， and treatment of extra-esophageal symptoms were discussed in depth. TCM and western medicine exchanged and complemented each other's strengths， combing the difficulties of modern medical diagnosis and treatment， which clarified the positioning and advantages of TCM and provided guidance for clinical and scientific research.

HBsAg is one of the oldest diagnostic markers for HBV infection, and serum HBsAg level is associated with HBV cccDNA level in hepatocytes, HBV replication capability, and host immune response. In recent years, with the development of serum HBsAg quantification and the concept of functional cure, HBsAg quantification has been taken more and more seriously in the clinical diagnosis and treatment of HBV infection. This article analyzes the role of serum HBsAg quantification from the aspects of natural disease course of chronic hepatitis B, prediction of response to antiviral therapy, and prediction of drug withdrawal.

OBJECTIVETo explore the temporal pattern of postmortem color changes in the pupil region of the cornea for noninvasive estimation of the postmortem interval (PMI).

METHODSTwo rabbit models of air embolism and drowning were established in a dark room at a temperature of 20 ℃ with a relative humidity of 30%. The corneal images of the rabbits were acquired using a digital camera at two-hour intervals within 72 h after death. The pupil region on the corneal images was segmented using computer image processing technique (MATLAB), and the parameters of 6 image color features (RGBHSV) were extracted. Regression analysis was used to analyze the relationship between these parameters and the PMI, and the effects of different death causes on the changes of the corneal color features were also assessed.

RESULTSWithin 72 h after death from different causes, the R, G and B values of the pupil region on the corneal images all tended to increase with the PMI, showing a good fitting with the PMI ( < 0.01). No significant correlation was found between the values of H, S and V and the PMI (>0.05). The R, G and B values in the pupil region on the corneal images showed consistent variation trends after death from the two causes, and their correlations with PMI were also similar. The measured values of R, G and B in air embolism group were greater than those in the drowning group.

CONCLUSIONSThe postmortem color changes of the pupil region on corneal images follow an identifiable temporal pattern and can vary across different causes of death. The regression equations established in this study provide references for non-invasive and objective estimation of the PMI.

Objective To investigate the relationship between subclinical hypothyroidism (SCH) and diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM).Methods A total of 792 patients of T2DM were enrolled in the study.There were 448 males and 344 females,with an average age of (54.13 ± 13.06)years.The average duration of diabetes was (8.03 4±6.70) years.The patients were grouped according to the degree of DR and thyroid function.Among them,483 patients (61.0％) were no DR,240 patients (30.3％) were mild DR,69 patients (8.7％) were severe DR.725 patients (91.5％) were normal thyroid function,67 patients (8.5％) were SCH.The prevalence of SCH among no DR group,mild DR group and severe DR group was compared.And the prevalence of DR between normal thyroid function group and SCH group was compared.Logistic regression analysis was used to estimate the association between SCH and DR.Results No significant differences among the three groups (no DR group,mild DR group,severe DR group) were found in the prevalence of SCH (x2=1.823,P=0.402).There were no significant differences in the incidences of DR between normal thyroid function group and SCH group (x2=1.618,P=0.239).Logistic regression analysis demonstrated that SCH was not significant associated with DR [mild DR:odds ratio (OR)=1.361,95％ confidence interval (CI)=0.773-2.399,P=0.286;severe DR:OR=1.326,95％CI=0.520-3.384,P=0.555;DR:OR=1.353,95％ CI=0.798-2.294,P=0.261).Conclusion SCH is not significant associated with DR in patients with T2DM.

OBJECTIVE:To observe the efficacy and safety of Shenqi jiangtang granule in the adjuvant treatment of type 2 dia-betes knee arthritis. METHODS:62 patients with type 2 diabetes knee arthritis were randomly divided into control group(31 cas-es) and observation group (31 cases). Control group received hypoglycemic and basic treatment for arthritis,including diet con-trol,exercise therapy and health education,as well as 0.25 g Metformin hydrochloride tablet with a meal,3 times a day + 50 mg Acarbose tablet with a meal,3 times a day,chewing;patients with arthritis pain 100 mg Aspirin enteric-coated tablet after a meal, once a day (chewing or breaking apart was prohibited). Observation group additionally received 3 g Shenqi jiangtang granule half an hour before a meal with 50 ml warm water,3 times a day. The treatment course for both groups was 6 months. Clinical effica-cy,and fasting plasma glucose(FPG),2 h postprandial blood glucose(2 h PG),glycated hemoglobin(HbA1c),interleukin-1β(IL-1β),IL-6 before and after treatment,and the incidence of adverse reactions in 2 groups were observed. RESULTS:The total effective rate in observation group was significantly higher than control group,the difference was statistically significant(P<0.05). Before treatment,there were no significant differences in the FPG,2 h PG,HbA1c,IL-1β and IL-6 between 2 groups(P>0.05). After treatment,FPG,2 h PG,HbA1c,IL-1β and IL-6 in 2 groups were significantly lower than before,and observation group was lower than control group,the differences were statistically significant(P<0.05). And there was no significant in the incidence of adverse reactions between 2 groups (P>0.05). CONCLUSIONS:Based on conventional treatment,Shenqi jiangtang granule shows obvious efficacy in the adjuvant treatment of type 2 diabetes knee arthritis.,it can reduce blood glucose and inflammation cy-tokine levels,mild symptoms of adverse reactions.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common diseases across the world, but there is still no specific treatment for NAFLD. Glucogon-like peptide 1 receptor agonist (GLP-1Ra) is a novel drug for the treatment of type 2 diabetes, based on incretin hormone target. Animal and clinical studies have demonstrated that GLP-1Ra can effec?tively reduce fat deposit in liver and attenuate hepatic steatosis. Therefore, GLP-1Ra is a promising therapeutic approachagainst NAFLD. In this review, we provided an overview of the clinical and basic research evidences and mechanisms in re?lieving NAFLD.

Objective To investigate the possible mechanisms of glucagon-like peptide 1 receptor agonists (GLP-1Ra) induced weight loss. Methods High fat diet induced obese c57BL/6 mice were divided into normal control group (N, n=8), high fat feeding group (HF, n=32) and GLP-1Ra group treated with GLP-1Ra (liraglutide 200μg/(kg·d) or 400μg/(kg·d) for 8 weeks). Changes of body weight, blood glucose and three acyl glycosides (TG) levels were observed in three groups. HE staining was used to observe the morphological changes. Immunofluorescence staining and real-time PCR were used to mea?sure the expression of UCP-1. Furthermore, the expression of PGC-1αin protein level was observed to explore the possible mechanism of GLP-1Ra induced browning in white fat (WAT). Results After 8-week liraglutide (Lira) administration, the body weights were significantly reduced in obese mice (P<0.05). The levels of blood glucose and TG were significantly high?er in HF group than those in N group, which reduced significantly in Lira (200μg·kg-1) and Lira (400μg·kg-1) administra?tion groups (P<0.05). HE staining showed adipocytes in perirenal and inguinal subcutaneous adipose tissue partly acquired brown-like morphological characteristics. The expression levels of UCP-1 protein and mRNA and PGC-1αprotein were ele?vated in adipse tissues, which increased more in Lira (400) than those in Lira (200, P<0.05). Conclusion GLP-1Ra can induce weight loss through white fat browning by activation of UCP-1.

Objective To investigate the possible mechanisms of glucagon-like peptide 1 receptor agonists (GLP-1Ra) protection against hyperglycemic induced beta cell apoptosis through depression of NOX2-dependent ROS production. Methods The rat model of type 2 diabetes (T2DM) was established by injecting small doses of streptozotocin (STZ) fol?lowed by 8-week high fat diet. The experimental animals were divided into three groups:normal control (N) group, diabetes (T2DM) group and GLP-1Ra group [treated with liraglutide 200 μg/(kg · d)for 12 weeks]. The blood glucose levels were compared before and after modeling, before treatment and 12-week after treatment with GLP-1Ra. The level of glycosylated hemoglobin (HbA1c) was detected by high-pressure liquid chromatography. Automatic biochemical analyzer was used to de?tect levels of aspertate aminotransferase (AST), creatinine (CR) and urea nitrogen (BUN). The apoptotic rates of islets were determined by TUNEL method and cleaved caspase 3 was detected by immunohistochemistry. DCFH-DA fluorescent probe was used to detect reactive oxygen species (ROS) levels of islets. Levels of NADPH oxidase (NOX) catalytic subunit (NOX 2) in islets were measured by immunohistochemistry. Results At the end of the study, glycemic control (average blood glucose/week and HbA1c) and lipid situation were improved significantly in the GLP-1Ra group than those of N group (P<0.05). TUNEL staining and displayed thatβcell apoptotic and cleaved caspase 3 level were significantly decreased in GLP-1Ra group compared to those of T2DM group (P<0.05). ROS levels were significantly decreased in GLP-1Ra group than those of T2DM group before treatment with Apocynin, but no significant difference between GLP1-Ra group and N group (P>0.05). After application Apocynin for inhibition, there were no significant differences between three groups (P>0.05). The level of NOX2 was significantly lower in GLP-1Ra group compared to that of T2DM group (P<0.05). Conclusion GLP-1Ra can inhibit apoptosis ofβcells in diabetes rat, and the depression of NOX2-dependent ROS may be one of the important underly?ing mechanisms.

Objective To investigate the mechanism of a dipeptidyl-peptidase-4 (DPP-4) inhibitor, saxagliptin, pro?moting the regeneration of islet beta cells in diabetic rats. Methods The male SD rats were randomly divided into three groups including control group (NC, n=10), diabetes group (DM, n=10) and diabetes treated with saxagliptin group (DM-S, n=10). DM-S group was treated with saxagliptin 1 mg/(kg·d) for twelve weeks. The pancreaticβcell function was analysed by hyperglycemic clamps. Immunohistochemistry with anti-PCNA was performed to observe the proliferation rate of pancreaticβcells. Immunofluorescence double staining with anti-insulin, anti-glucagon, anti-DPP-4 and anti-SDF-1 were performed to observe the expression of insulin, glucagon, DPP-4 and SDF-1 in pancreatic tissue. Western blot assay was performed to test the expression of Akt, p-Akt,β-catenin and free-β-catenin protein, and RT-PCR was performed to test the expressionlevels of c-myc and cyclinD1 mRNA in pancreatic tissue. Results Compared with NC group, there were significantly in?creased blood glucose, decreased islet function andβcell mass in DM group. Compared with DM rats, saxagliptin treatment significantly inhibited the expression of DPP-4, decreased the degradation of SDF-1, stimulated the proliferation ofβcells, and ultimately improved the islet function and histopathological changes of pancreas. Conclusion DPP-4 inhibitor saxa?gliptin can significantly improve islet function, which involved in the inhibition of the expression of DPP-4, the decreased degradation of SDF-1 and the stimulation of the proliferation ofβcells.