Tumor microenvironment(TME)is the foundation for tumor survival,which is composed of various types of cells,tumor blood vessels,secretory factors,and extracellular matrix(ECM)within the tumor.The unique regulatory mechanism triggered by the vigorous metabolic demand of tumor plays an important role in its tumorigenesis,metastasis,invasion,and treatment resistance.A deeper understanding of the metabolic transformation and tumor-immune cell interactions in the TME will enable the development of therapeutic technologies that precisely target TME metabolism,facilitate the development of combination treatment strategies,and improve the clinical response rate of existing immunotherapies.This paper reviews the composition,metabolism and regulatory mechanisms of TME,summarizes the research progress of immunotherapy strategies targeting the physiological characteristics of TME,and discusses the prospects for clinical application of precision immunotherapy strategies targeting TME,which are expected to enhance immunotherapy drugs response and infiltration degree.

Aim To evaluate the bioequivalence of two oral preparations of rivaroxaban tablets(test preparation T and refe-rence preparation R)in fasting/postprandibular state in healthy Chinese subjects.Methods A randomized,open,single-dose,four-cycle,completely repeated crossover experiment was used in this study.A total of 70 healthy male and female subjects were enrolled,including 38 subjects in the fasting group and 32 sub-jects in the postprandial group.Rivaroxaban tablets(2.5 mg/tablet)were taken orally once per cycle and their reference preparations were tested.The plasma rivaroxaban concentration was determined by LC-MS/MS method.The pharmacokinetic parameters of rivaroxaban tablets were calculated by WinNonlin software,and the parameters were analyzed and processed.Re-sults The PK parameters of rivaroxaban tablets and reference preparations in fasting group were as follows:Cmax was(72.48±17.08)and(66.36±15.64)μg·L-1,respectively.AUC0-t were(383.49±101.06)and(370.43±102.16)h·ng·mL-1,and AUC0-inr were(389.58±102.28)and(375.84±103.01)h·μg·L-,respectively.Main PK parameters of subjects taking rivaroxaban tablets orally after meals:Cmax were(66.48±15.64 and 60.87±13.44)μg·L-1,AUC0-t were(404.44±72.58)and(381.80±79.93)h·μg·L-1,re-spectively.AUC0_inf was(410.88±73.55)and(393.64±69.71)h·μg·L-1,respectively.Under fasting and postmeal conditions,subjects took rivaroxaban test and reference prepara-tion orally,one tablet(2.5 mg/tablet)each time.The geometric mean of the main pharmacokinetic parameters of rivaroxaban in plasma(Cmax,AUC0-t,AUC0-inf)and their corresponding values had a 90％confidence interval ranging from 80.00％to 125.00％.No serious adverse events or unexpected adverse e-vents occurred in both groups.Conclusion Rivaroxaban tablets are bioequivalent and safe in vivo under fasting and postprandial conditions.

Aim To investigate the anti-acute lung injury(ALI)effect of Sterculiae Lychnophorae Semen(SLS)and its mechanism.Methods The main ac-tive components of SLS and their core targets and path-ways of action against ALI were obtained by network pharmacology methods.Subsequently,molecular doc-king technology and in vitro cellular experiments were applied for validation.Results A total of 19 core tar-gets were obtained,including HSP90AA1,CASP3,TNF,MAPK8 and MAPK14.The mechanisms may in-volve signaling pathways such as cancer,PI3K/Akt and MAPK.Molecular docking confirmed that the key targets of SLS formed a better binding activity with the relevant active ingredients.The in vitro results showed that SLS was able to protect the PM2.5-contaminated BEAS-2B cells,inhibit their NO,IL-1β and TNF-αlevels,and reduce the expression of p-p38 MAPK and p-JNK proteins.Conclusions The study successfully predicts the active ingredients,targets and signaling pathways of SLS against ALI,and in vitro experiments demonstrate that SLS might protect BEAS-2B cells from PM2.5 stimulus-induced inflammation and apoptosis by inhibiting the over-activation of p38 MAPK and JNK signaling pathways.

Aim To evaluate the bioequivalence of two oral preparations of rivaroxaban tablets(test preparation T and refe-rence preparation R)in fasting/postprandibular state in healthy Chinese subjects.Methods A randomized,open,single-dose,four-cycle,completely repeated crossover experiment was used in this study.A total of 70 healthy male and female subjects were enrolled,including 38 subjects in the fasting group and 32 sub-jects in the postprandial group.Rivaroxaban tablets(2.5 mg/tablet)were taken orally once per cycle and their reference preparations were tested.The plasma rivaroxaban concentration was determined by LC-MS/MS method.The pharmacokinetic parameters of rivaroxaban tablets were calculated by WinNonlin software,and the parameters were analyzed and processed.Re-sults The PK parameters of rivaroxaban tablets and reference preparations in fasting group were as follows:Cmax was(72.48±17.08)and(66.36±15.64)μg·L-1,respectively.AUC0-t were(383.49±101.06)and(370.43±102.16)h·ng·mL-1,and AUC0-inr were(389.58±102.28)and(375.84±103.01)h·μg·L-,respectively.Main PK parameters of subjects taking rivaroxaban tablets orally after meals:Cmax were(66.48±15.64 and 60.87±13.44)μg·L-1,AUC0-t were(404.44±72.58)and(381.80±79.93)h·μg·L-1,re-spectively.AUC0_inf was(410.88±73.55)and(393.64±69.71)h·μg·L-1,respectively.Under fasting and postmeal conditions,subjects took rivaroxaban test and reference prepara-tion orally,one tablet(2.5 mg/tablet)each time.The geometric mean of the main pharmacokinetic parameters of rivaroxaban in plasma(Cmax,AUC0-t,AUC0-inf)and their corresponding values had a 90％confidence interval ranging from 80.00％to 125.00％.No serious adverse events or unexpected adverse e-vents occurred in both groups.Conclusion Rivaroxaban tablets are bioequivalent and safe in vivo under fasting and postprandial conditions.

Objective To analyze differences of purified water,softened water,and concentrated softened water on the decontamination effects for surgical instruments,so as to provide a reliable reference for the selection of cleaning water for surgical instruments.Methods The physical and chemical indexes and components of concentrated softened water,softened water,and purified water were detected,and their cleaning effects for instrument were compared.The decontamination cleaning experiment was conducted in three hospitals with different types of cleaning water using mini cleaning machines,and the differences in the decontamination time were analyzed.The cleaning and decontamination experiments on contaminated instruments was performed using a spray cleaning and disinfection device,and the cleaning effects of instruments with different types of cleaning water were analyzed.Results Calcium content and hardness of the three types of cleaning water were all at a low level,which can avoid scale adhesion for cleaning surgical instruments.There were statistically significant differences in the pH value,conductivity,and contents of calcium,sodium and chloride among the three cleaning waters(P<0.05).The purified water was weakly acidic,and its conductivity,hardness,and contents of calcium,sodium and chloride were all at low levels.The softened water and concentrated softened water were weakly alkaline,with high levels of conductivity and sodium content and low level of chloride.There were statistically significant differences in the decontamination time of the purified water,softened water and concentrated softened water among hospitals(P<0.05).Under the same contamination condition of surgical instruments,there was a statistically significant difference in the qualified rate of instruments cleaning in the upper and lower cleaning baskets with different cleaning waters(P<0.05).Conclusion Concentrated softened water and softened water have high sodium content,and their decontamination and cleaning abilities are significantly stronger than those of the purified water.Purified water has poorer effects in instruments cleaning for its deionized property.Using concentrated softened water or softened water in the surgical instrument cleaning process can achieve effects of reducing consumption and increasing efficiency,which is conducive to improving cleaning efficiency and quality.

Objective To analyze differences of purified water,softened water,and concentrated softened water on the decontamination effects for surgical instruments,so as to provide a reliable reference for the selection of cleaning water for surgical instruments.Methods The physical and chemical indexes and components of concentrated softened water,softened water,and purified water were detected,and their cleaning effects for instrument were compared.The decontamination cleaning experiment was conducted in three hospitals with different types of cleaning water using mini cleaning machines,and the differences in the decontamination time were analyzed.The cleaning and decontamination experiments on contaminated instruments was performed using a spray cleaning and disinfection device,and the cleaning effects of instruments with different types of cleaning water were analyzed.Results Calcium content and hardness of the three types of cleaning water were all at a low level,which can avoid scale adhesion for cleaning surgical instruments.There were statistically significant differences in the pH value,conductivity,and contents of calcium,sodium and chloride among the three cleaning waters(P<0.05).The purified water was weakly acidic,and its conductivity,hardness,and contents of calcium,sodium and chloride were all at low levels.The softened water and concentrated softened water were weakly alkaline,with high levels of conductivity and sodium content and low level of chloride.There were statistically significant differences in the decontamination time of the purified water,softened water and concentrated softened water among hospitals(P<0.05).Under the same contamination condition of surgical instruments,there was a statistically significant difference in the qualified rate of instruments cleaning in the upper and lower cleaning baskets with different cleaning waters(P<0.05).Conclusion Concentrated softened water and softened water have high sodium content,and their decontamination and cleaning abilities are significantly stronger than those of the purified water.Purified water has poorer effects in instruments cleaning for its deionized property.Using concentrated softened water or softened water in the surgical instrument cleaning process can achieve effects of reducing consumption and increasing efficiency,which is conducive to improving cleaning efficiency and quality.

Aim To investigate the anti-acute lung injury(ALI)effect of Sterculiae Lychnophorae Semen(SLS)and its mechanism.Methods The main ac-tive components of SLS and their core targets and path-ways of action against ALI were obtained by network pharmacology methods.Subsequently,molecular doc-king technology and in vitro cellular experiments were applied for validation.Results A total of 19 core tar-gets were obtained,including HSP90AA1,CASP3,TNF,MAPK8 and MAPK14.The mechanisms may in-volve signaling pathways such as cancer,PI3K/Akt and MAPK.Molecular docking confirmed that the key targets of SLS formed a better binding activity with the relevant active ingredients.The in vitro results showed that SLS was able to protect the PM2.5-contaminated BEAS-2B cells,inhibit their NO,IL-1β and TNF-αlevels,and reduce the expression of p-p38 MAPK and p-JNK proteins.Conclusions The study successfully predicts the active ingredients,targets and signaling pathways of SLS against ALI,and in vitro experiments demonstrate that SLS might protect BEAS-2B cells from PM2.5 stimulus-induced inflammation and apoptosis by inhibiting the over-activation of p38 MAPK and JNK signaling pathways.

Tumor microenvironment(TME)is the foundation for tumor survival,which is composed of various types of cells,tumor blood vessels,secretory factors,and extracellular matrix(ECM)within the tumor.The unique regulatory mechanism triggered by the vigorous metabolic demand of tumor plays an important role in its tumorigenesis,metastasis,invasion,and treatment resistance.A deeper understanding of the metabolic transformation and tumor-immune cell interactions in the TME will enable the development of therapeutic technologies that precisely target TME metabolism,facilitate the development of combination treatment strategies,and improve the clinical response rate of existing immunotherapies.This paper reviews the composition,metabolism and regulatory mechanisms of TME,summarizes the research progress of immunotherapy strategies targeting the physiological characteristics of TME,and discusses the prospects for clinical application of precision immunotherapy strategies targeting TME,which are expected to enhance immunotherapy drugs response and infiltration degree.

Traditional Chinese Medicine (TCM), as a treasure of the Chinese nation, plays a significant role in maintaining public health. In 2019, the Central Committee of the Communist Party of China and the State Council proposed for the first time the establishment of a TCM registration and evaluation evidence system that integrates TCM theory, "personal experience" and clinical trials (referred to as the "Three-in-One" System) to promote the inheritance and innovation of TCM. Subsequently, the National Medical Products Administration issued several guiding principles to advance the improvement and implementation of this system. Owing to the complexity of its implementation, there are still differing understandings within the TCM industry regarding the positioning of the "Three-in-One" Registration and Evaluation Evidence System, as well as the connotation and value orientation of the "personal experience." To address this, Academician WANG Qi, President of the TCM Association, China International Exchange and Promotion Association for Medical and Healthcare and TCM master, led a group of academicians, TCM masters, TCM pharmacology experts and clinical TCM experts to convene a "Seminar on Promoting the Implementation of the ′Three-in-One′ Registration and Evaluation Evidence System for Chinese Medicinals." Through extensive discussions, an expert consensus was formed, clarifying the different roles of the TCM theory, "personal experience" and clinical trials within the system. It was further emphasized that the "personal experience" is the core of this system, and its data should be derived from clinical practice scenarios. In the future, the improvement of this system will require collaborative efforts across multiple fields to promote the high-quality development of the Chinese medicinal industry.

OBJECTIVE: Observational studies have found associations between inflammatory bowel disease (IBD) and the risk of dementia, including Alzheimer's dementia (AD) and vascular dementia (VD); however, these findings are inconsistent. It remains unclear whether these associations are causal. METHODS: We conducted a meta-analysis by systematically searching for observational studies on the association between IBD and dementia. Mendelian randomization (MR) analysis based on summary genome-wide association studies (GWASs) was performed. Genetic correlation and Bayesian co-localization analyses were used to provide robust genetic evidence. RESULTS: Ten observational studies involving 80,565,688 participants were included in this meta-analysis. IBD was significantly associated with dementia (risk ratio [ RR] =1.36, 95% CI = 1.04-1.78; I ² = 84.8%) and VD ( RR = 2.60, 95% CI = 1.18-5.70; only one study), but not with AD ( RR = 2.00, 95% CI = 0.96-4.13; I ² = 99.8%). MR analyses did not supported significant causal associations of IBD with dementia (dementia: odds ratio [ OR] = 1.01, 95% CI = 0.98-1.03; AD: OR = 0.98, 95% CI = 0.95-1.01; VD: OR = 1.02, 95% CI = 0.97-1.07). In addition, genetic correlation and co-localization analyses did not reveal any genetic associations between IBD and dementia. CONCLUSION Our study did not provide genetic evidence for a causal association between IBD and dementia risk. The increased risk of dementia observed in observational studies may be attributed to unobserved confounding factors or detection bias.
Humans ; Mendelian Randomization Analysis ; Inflammatory Bowel Diseases/complications* ; Dementia/etiology* ; Observational Studies as Topic ; Genome-Wide Association Study