Heat shock protein 70 (HSP70), an evolutionarily conserved molecular chaperone, serves as a central regulator within tumor immune networks. This review summarizes the multiple immune regulatory mechanisms mediated by HSP70 through its specific domains: promoting antigen presentation and cross-presentation processes; prolonging immune response duration; regulating innate and adaptive immune responses; and interacting with immune checkpoint molecules like programmed death-1 ligand 1 (PD-L1). In translation of clinical research, HSP70 can serve as a vaccine adjuvant to enhance immunogenicity, while its inhibitors can overcome resistance to immunotherapy. Additionally, membrane-bound HSP70 represents a potential immunotherapeutic target, and its targeting strategies show significant synergistic effects when combined with immune checkpoint inhibitors. However, due to the functional redundancy of the molecular chaperone network, the clinical efficacy of single-agent HSP70 inhibition is limited. In-depth elucidation of HSP70's synergistic regulatory mechanisms within the chaperone interaction network has important implications for developing novel tumor immunotherapy strategies.
HSP70 Heat-Shock Proteins/metabolism* ; Humans ; Immunotherapy/methods* ; Neoplasms/immunology* ; Animals ; B7-H1 Antigen/metabolism*

Objective:To develop the certified reference material of cadmium in human urine (freeze-dried) .Methods:Urine were collected from normal human, and then the urine samples were prepared by adding standard, mixing, packing and freeze-drying. After homogeneity test and stability test, the urine samples were determined by two methods in seven independent laboratories, the uncertainty of the certified reference material was evaluated.Results:Take at least 0.20 ml solution of the certified reference material per use, and the homogeneity is good. The freeze-dried materials can be kept stable for 12 months at ≤4 °C, and the re-dissolved reference materials can be stabilized for 7 days at 4 °C. The standard values and uncertainty of the two levels were (5.34±0.34) μg/L and (15.47±0.72) μg/L, respectively.Conclusion:The standards met the requirements of national standards, and can be used to verify the methods of detecting cadmium in human urine and to detect the samples.

Objective:To develop a reference material for the analysis of mercury in freeze-dried bovine blood.Methods:The whole blood of the bovine was collected, mercury standard solution was added, After mixing, packaging and freeze-drying. Two concentration levels of reference materials were prepared. The homogeneity and stability were evaluated by t-test and F-test methods respectively. The uncertainty in preparation, long-term stability, short-term stability and fixed value were evaluated Evaluation and assignment of reference materials. The research products were fixed value and were analyzed by two methods and fixed value in 9 laboratories and the uncertainty during development was analyzed.Results:The reference material has good uniformity and can be kept stably for 12 months at -20 ℃; When transported at ≤35 ℃, the quantity value is stable within 7 days; After re dissolution, it can be stored at 4 ℃ for 5 days; The values are 9.4 respectively μg/L and 29.2 μg/L, and the uncertainty is ±1.1 respectively μg/L and ±2.3 μg/L ( k=2) . Conclusion:The indexes of reference materials for mercury composition analysis in freeze-dried bovine blood meet the requirements of technical specifications and have certain application value.

Objective:To develop the certified reference material of cadmium in human urine (freeze-dried) .Methods:Urine were collected from normal human, and then the urine samples were prepared by adding standard, mixing, packing and freeze-drying. After homogeneity test and stability test, the urine samples were determined by two methods in seven independent laboratories, the uncertainty of the certified reference material was evaluated.Results:Take at least 0.20 ml solution of the certified reference material per use, and the homogeneity is good. The freeze-dried materials can be kept stable for 12 months at ≤4 °C, and the re-dissolved reference materials can be stabilized for 7 days at 4 °C. The standard values and uncertainty of the two levels were (5.34±0.34) μg/L and (15.47±0.72) μg/L, respectively.Conclusion:The standards met the requirements of national standards, and can be used to verify the methods of detecting cadmium in human urine and to detect the samples.

Objective:To develop a reference material for the analysis of mercury in freeze-dried bovine blood.Methods:The whole blood of the bovine was collected, mercury standard solution was added, After mixing, packaging and freeze-drying. Two concentration levels of reference materials were prepared. The homogeneity and stability were evaluated by t-test and F-test methods respectively. The uncertainty in preparation, long-term stability, short-term stability and fixed value were evaluated Evaluation and assignment of reference materials. The research products were fixed value and were analyzed by two methods and fixed value in 9 laboratories and the uncertainty during development was analyzed.Results:The reference material has good uniformity and can be kept stably for 12 months at -20 ℃; When transported at ≤35 ℃, the quantity value is stable within 7 days; After re dissolution, it can be stored at 4 ℃ for 5 days; The values are 9.4 respectively μg/L and 29.2 μg/L, and the uncertainty is ±1.1 respectively μg/L and ±2.3 μg/L ( k=2) . Conclusion:The indexes of reference materials for mercury composition analysis in freeze-dried bovine blood meet the requirements of technical specifications and have certain application value.

Objective:To observe the effect of comprehensive rehabilitation training in a group on the speech and life quality of stroke survivors with dysarthria.Methods:Stroke survivors with dysarthria were randomly divided into an observation group (of 43) and a control group (of 41). In addition to routine medication, the control group was given 30 minutes of one-to-one rehabilitation training twice a day, 6 days a week for 4 weeks while the observation group was provided with 30 minutes of group training. Before and after the intervention, both groups were evaluated using the comprehensive dysarthria assessment scale and the WHOQOL-100 life quality assessment.Results:After the treatment, both groups′ average scores on the comprehensive assessment scale had improved significantly. Except for jaw positioning, all of the observation group′s other scores were significantly better than those of the control group, on average. The observation group also performed significantly better on the WHOQOL-100 assessment, on average.Conclusions:Group rehabilitation training can improve the speech function and life quality of stroke survivors with dysarthria significantly better than one-to-one training.

Objective To investigate the effects and the mechanism of thrombospondin 4 (Thbs4) gene-edited bone marrow mesenchymal stem cells (BMSCs) transplantation on vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1) in diabetic rats with hind limb ischemia. Methods Thirty Sprague-Dawley rats were randomly divided into the model group, BMSCs treatment group and Thbs4-BMSCs treatment group on average. After constructing the typeⅡdiabetic rat model with hind limb ischemia, 100μl normal saline, BMSCs suspension and Thbs4-BMSCs suspension (cell number: 2×106) were locally injected into the ischemic injury area of rats for the model group, BMSCs group and Thbs4-BMSCs group, respectively. The rats were sacrificed on the 14th day after stem cell transplantation, and the muscle tissues near the ischemic area were collected. The relative expression of VEGF and p-Smad2/3 protein was detected by Western Blot. The Ang-1 protein expression was detected by immunofluorescence staining. The levels of related genes were detected by qRT-PCR, and the von Willebrand Factor (vWF) protein expression was detected by immunohistochemistry staining. Results The relative expression levels of VEGF, Ang-1 and vWF protein in the Thbs4-BMSCs group were significantly higher than those in the model group and BMSCs group (VEGF protein:P<0.01 and P<0.05). The mRNA expression of VEGF and Ang-1 were significantly up-regulated, the differences were statistically significant(VEGF mRNA:all P<0.01;Ang-1:P<0.01 and P<0.05). The expression of p-Smad2/3 protein in the Thbs4-BMSCs group was significantly higher than that in the model group and the BMSCs treatment group (all P<0.01). The expression of p-Smad2/3 protein was significantly decreased after the addition of p-Smad2/3 pathway inhibitor, the differences were statistically significant (P<0.05). Conclusions Thbs4-BMSCs transplantation can effectively promote angiogenesis in diabetic rats with hind limb ischemia, and the effect of angiogenesis may be related to the activation of Smad2/3 signaling pathway.

Objective: To analyze the results obtained from the proficiency testing program for determination of bovine blood lead and urinary cadmium, so as to evaluate the proficiency of the laboratories, and improve the detection and quality control capability of occapational health laboratory. Methods: Prepared 3 levels of lead samples with bovine blood as base material, taking Technical Norm of Primary Reference Material as Operating standard, 60, 80, 180 μg/L were used as the standard concentration. All samples were made for 200 bottles. Normal urine were used to prepared 3 levels of cadmium samples with 5.0, 7.0, 10.0 μg/L as standard concentration, then 3 level of samples were made for 200 bottles respectively. Blood lead and urinary cadmium samples were sent to each laboratory in the form of sample pairs. One-way ANOVA was used to investigate the homogeneity. The results of each laboratory were statistically analyzed by robust statistical method, and the detection ability of the laboratory was evaluated by the Z ratio score method. By consulting the test reports and original records of each participating laboratory, the reasons for the unsatisfactory results were analyzed. Results: The statistical F of the uniformity of blood lead 1.42, 1.37 and 2.85, F<3.13, P were 0.294, 0.314 and 0.059, respectively in 31 labs. There is no statistical significance in the difference of blood lead (P>0.05). And urine cadmium was less than the critical value (P>0.05). In all, 31 laboratories participated in the test of blood lead, and 28 loboratories paticipated in urine cadmium verification. The statistical F of the uniformity of urinary cadmium 1.90, 1.35 and 1.19, F<3.13. The homogeneity of the samples were in accordance with the requirements of proficiency testing program. The satisfactory rate of the results for blood lead was 84% (26/31) , and the satisfactory rate of urinary cadmium was 93% (26/28) . In the test of blood lead, 21 of the 31 laboratories were controlled by the standard material method. Totally, 20 of them get an satisfactory level, the rate was 95%. Conclusion Most of the laboratory test results were satisfactory, which showed that the detection capability for blood lead and urine cadmium was good. The main causes of unsatisfactory results were detection methods, tools of quality control ortraceability standards.

Objective: Through inter-laboratory comparison to analysis and evaluation of the detection capacity of arsenic in the urine. Methods: Urine arsenic samples were prepared with normal human urine as matrix. The homogeneity of the samples was investigated and the results were statistically analyzed by single factor analysis of variance. 2 samples were issued to each participant laboratory. A robust statistical four-point distance method was used to calculate the results submitted by each participant laboratory and the test capability of the laboratory was assessed by the z-score method. By means of method experiments and records, the reasons of dissatisfaction and the influencing factors of the results were discussed. Results: The statistic of the homogeneity of urine arsenic samples was less than the critical value (P>0.05) , which showed that the arsenic in the sample was homogeneous. The satisfactory rate of comparison between 36 laboratories was 86.1%. The main reasons for dissatisfaction were the testing conditions and the quality control measures. The selection of sample pretreatment, acidity control and hydrogenation conditions was the main influencing factor for the determination of urinary arsenic by atomic fluorescence spectrometry. Conclusion The level of urinary arsenic detection in the occupational health laboratories was generally better and a few laboratories need to be improved ability of detection. It was very important to control the test conditions reasonably and strengthen the quality control measures to improve the accuracy of urine arsenic detection.

Objective: To optimize the ion selective electrode method of measuring urinary fluorine in WS/T 30-1996. Methods: The volume of 5 mol/L NaOH solution was fixed to confect the TISAB buffer solution. The samples were prepared by mixing 5 ml urine and equal volume of TISAB solution. Fluorine electrode and calomel electrode was used to test. When the potential value changed less than ±0.5 mV in one minute, it could be recorded. The standard curve method was selected as a quantitive method. Results: The linear range of this method was 0.07~50.0 mg/L, E=238.96-57.50lgC, r=0.999 8. The LOD and LOQ were 0.02 mg/L and 0.07 mg/L (with 5 ml urine) , respectively. The RSD of intra -and inter-batch precision were 0.80%~2.82% and 2.17%~2.86%, respectively. The recovery rate was 102%~107%. The urine sample could be preserved stably for 14 days at room temperature, and for 30 days at 4 ℃ and -20 ℃. Conclusion In this method, the preparation process of TISAB buffer solution was simplified, and the linear range was expanded. It could meet the needs of occupational population detection.