T cell exhaustion plays an immunosuppressive role in malignant tumors. Continuous tumor antigen stimulation, the presence of suppressive immune cells and cytokines in the tumor microenvironment, the up regulation of inhibitory receptor expression on the surface of T cells, changes in T cell related transcription factors, and metabolites in the tumor microenvironment may lead to T cell exhaustion. Reversing the exhaustion of T cells in tumor patients is a promising strategy for tumor immunotherapy. This article will review the latest research progress on T cell exhaustion status, pathogenesis, reversal methods, and clinical applications in hematological tumors.
Humans ; Hematologic Neoplasms/immunology* ; T-Lymphocytes/immunology* ; Tumor Microenvironment ; Immunotherapy ; T-Cell Exhaustion

OBJECTIVE: To evaluate the immediate effect of Kuanxiong Aerosol (KXA) on perioperative coronary microcirculation in patients with unstable angina (UA) suffering from elective percutaneous coronary intervention (PCI). METHODS: From February 2021 to July 2023, UA inpatients who underwent PCI alone in the left anterior descending (LAD) branch were included. Random numbers were generated to divide patients into the trial group and the control group at a ratio of 1:1. The index of coronary microcirculation resistance (IMR) was measured before PCI, and the trial group was given two sprays of KXA, while the control group was not given. IMR was measured again after PCI, cardiac troponin I (cTnI) and creatine kinase isoenzyme-MB (CK-MB) were detected before and 24 h after surgery, and major cardiovascular adverse events (MACEs) were recorded for 30 days. The data statistics and analysis personnel were blinded. RESULTS: Totally 859 patients were screened, and 62 of them were involved into this study. Finally, 1 patient in the trial group failed to complete the post-PCI IMR and was excluded, 30 patients were included for data analysis, while 31 patients in the control group were enrolled in data analysis. There was no significant difference in baseline data (age, gender, risk factors, previous history, biochemical index, and drug therapy, etc.) between the two groups. In addition, differences in IMR, cTnI and CK-MB were not statistically significant between the two groups before surgery. After PCI, the IMR level of the trial group was significantly lower than that of the control group (19.56 ± 14.37 vs. 27.15 ± 15.03, P=0.048). Besides, the incidence of perioperative myocardial injury (PMI) was lower in the trial group, but the difference was not statistically significant (6.67% vs. 16.13%, P=0.425). No MACEs were reported in either group. CONCLUSIONS KXA has the potential of improving coronary microvascular dysfunction. This study provides reference for the application of KXA in UA patients undergoing elective PCI. (Registration No. ChiCTR2300069831).
Humans ; Percutaneous Coronary Intervention ; Male ; Microcirculation/drug effects* ; Female ; Angina, Unstable/physiopathology* ; Pilot Projects ; Middle Aged ; Aged ; Drugs, Chinese Herbal/pharmacology* ; Aerosols ; Troponin I/blood* ; Coronary Circulation/drug effects* ; Elective Surgical Procedures

Objective: To explore the relationship between processed food consumption and blood pressure level of students in a university in Yunnan Province, so as to provide the reference for preventing hypertension in university students. Methods: In October 2021, a cluster sampling method was used to select 4 781 freshmen from a university in Kunming, Yunnan Province. The frequency of processed food consumption of university students was assessed by using the dietary frequency questionnaire, and height, weight and blood pressure were measured. Mann-Whitney test and Kruskal-Wallis test were used to compare the differences in blood pressure level of university students with different demographic variables, and the association between processed food consumption and blood pressure level was analyzed with a generalized linear model. Results: Among the students of a university in Yunnan Province, the detection rates of systolic prehypertension and hypertension were 33.86% and 1.23%, and the detection rates of diastolic prehypertension were 32.13% and hypertension 7.22%. The results of generalized linear model analysis showed that after controlling for demographic variables and other variables that might affect the blood pressure level of university students, the consumption of processed food (bread and cake: β =0.15, 95% CI =0.01-0.29) and ultra processed food (coffee beverage: β =-0.29, 95% CI =-0.54--0.03) were associated with systolic blood pressure level( P <0.05). The consumption of processed food (salted duck egg: β =0.21, 95% CI =0.01-0.41) was correlated with the diastolic blood pressure of college students ( P <0.05). Conclusions Processed food consumption in university students may increase the risk of high blood pressure.The education of healthy eating among college students should be strengthened to reduce the consumption of processed foods.

ObjectiveThe absorption of substances into blood is mainly dependent on the mesenteric lymphatic pathway and the portal venous pathway. The substances transported via the portal venous pathway can be metabolized by the biotransformation in the liver. On the contrary, the substances in the mesenteric lymph fluid enter the blood circulation without biotransformation and can affect the body directly. Alcohol consumption is strongly linked to global health risk. Previous reports have analyzed the changes of metabolites in plasma, serum, urine, liver and feces after alcohol consumption. Whether alcohol consumption affects the metabolites in lymph fluid is still unknown. Therefore, it is particularly important to explore the changes of substances transported via the mesenteric lymphatic pathway and analyze their harmfulness after alcohol drinking. MethodsIn this study, male Wistar rats were divided into high, medium, and low-dosage alcohol groups (receiving Chinese Baijiu at 56%, 28% and 5.6% ABV, respectively) and water groups. The experiment was conducted by alcohol gavage lasting 10 d, 10 ml·kg^-1·d^-1. Then mesenteric lymph fluid was collected for non-targeted metabolomic analysis by using liquid chromatography-mass spectrometry (LC-MS) and bioinformatic analysis. Principal component analysis and hierarchical clustering were performed by using Biodeep. Meanwhile, KEGG enrichment analysis of the differential metabolites was also performed by Biodeep. MetaboAnalyst was used to analyze the relationship between the differential metabolites and diseases. ResultsThe metabolites in the mesenteric lymph fluid of the high-dosage alcohol group change the most. Based on the KEGG enrichment analysis, the pathways of differential metabolites between the high-dosage alcohol group and the control group are mainly enriched in the central carbon metabolism in cancer, bile secretion, linoleic acid metabolism, biosynthesis of unsaturated fatty acids, etc. Interestingly, in the biosynthesis of unsaturated fatty acids category, the content of arachidonic acid is increased by 7.25 times, whereas the contents of palmitic acid, oleic acid, stearic acid, arachidic acid and erucic acid all decrease, indicating lipid substances in lymph fluid are absorbed selectively after alcohol intake. It’s worth noting that arachidonic acid is closely related to inflammatory response. Furthermore, the differential metabolites are mainly related with schizophrenia, Alzheimer’s disease and lung cancer. The differential metabolites between the medium-dosage alcohol and the control group were mainly enriched in phenylalanine metabolism, valine, leucine and isoleucine biosynthesis, linoleic acid metabolism and cholesterol metabolism. The differential metabolites are mainly related to schizophrenia, Alzheimer’s disease, lung cancer and Parkinson’s disease. As the dose of alcohol increases, the contents of some metabolites in lymph fluid increase, including cholesterol, L-leucine, fumaric acid and mannitol, and the number of metabolites related to schizophrenia also tends to increase, indicatingthat some metabolites absorbed by the intestine-lymphatic pathway are dose-dependent on alcohol intake. ConclusionAfter alcohol intake, the metabolites transported via the intestinal-lymphatic pathway are significantly changed, especially in the high-dosage group. Some metabolites absorbed via the intestinal-lymphatic pathway are dose-dependent on alcohol intake. Most importantly, alcohol intake may cause inflammatory response and the occurrence of neurological diseases, psychiatric diseases and cancer diseases. High-dosage drinking may aggravate or accelerate the occurrence of related diseases. These results provide new insights into the pathogenesis of alcohol-related diseases based on the intestinal-lymphatic pathway.

In order to study the compounds from Glechoma longituba (Nakai) Kupr. and explore the substance bases of its dissipating blood stasis, MCI, silica gel, Sephadex LH-20, ODS column chromatography and preparative thin layer chromatography were used to isolate and purify the compounds. The structures were identified by MS, 1D NMR, and 2D NMR spectra analysis, etc. Eight triterpenoids were isolated from dichloromethane fraction of ethanol extract from G. longituba and identified as 2α,3α,16β-trihydroxy-13α,27-cyclours-11-en-28-oic acid (1), 28-norurs-12-ene-3β,17β-diol (2), 28-norolean-12-ene-3β,17β-diol (3), oleanonic acid (4), 3β,13β-dihydroxyurs-11-en-28-oic acid (5), uvaol (6), oleanolic acid (7), ursolic acid (8). Compound 1 is a new hexacyclic triterpene with 13α,27-cyclopropane structure, named euscaphic acid H; compounds 2 and 3 were isolated from Lamiaceae for the first time while compounds 4 and 5 were isolated from this genus. The in vitro anticoagulant activity of triterpenoids was evaluated by four coagulation indexes (activated partial thromboplastin time, APTT; thrombin time, TT; prothrombin time, PT; fibrinogen, FIB). Among them, compounds 1 and 6 showed obvious anticoagulant effects.

Methamphetamine (METH) is a powerful stimulant drug that can cause addiction and serious health problems. It is one of the most widely abused drugs in the world. However, the mechanisms of how METH affects the brain and leads to addiction are still unclear, and there are no effective treatments for METH addiction in clinical practice. Therefore, it is important to explore the new addiction mechanisms and treatment strategies of METH. METH addiction is a complex and chronic brain disorder that involves multiple brain regions and neurotransmitter systems. Neurotransmitters are chemical messengers that transmit signals between neurons (nerve cells) in the brain. Some of the main neurotransmitters involved in METH addiction are dopamine (DA), glutamate (Glu), norepinephrine (NE), and serotonin (SNRIS). These neurotransmitters regulate various aspects of brain function, such as reward, reinforcement, motivation, cognition, emotion, and behavior. When a person takes METH, it causes a surge of these neurotransmitters in the brain, especially in the prefrontal cortex (mPFC), ventral tegmental area (VTA), and nucleus accumbens (NAc). These brain regions form a circuit called the mesocorticolimbic system, which is responsible for mediating the rewarding and reinforcing effects of drugs and natural stimuli. The increased levels of neurotransmitters in this circuit make the person feel euphoric, alert, confident, and energetic. However, repeated or chronic use of METH can also cause negative effects, such as anxiety, paranoia, psychosis, depression, and cognitive impairment. The effects of METH on the brain are not only due to the changes in neurotransmitter levels, but also to the changes in gene expression. Gene expression is the process by which genes are turned on or off to produce proteins that perform various functions in the cells. Gene expression can be influenced by environmental factors, such as drugs, stress, diet, etc. One way that environmental factors can affect gene expression is through epigenetic mechanisms. Epigenetics is a branch of genetics that studies the heritable changes in gene expression that are not caused by changes in DNA sequence. Epigenetic mechanisms include histone modifications, DNA methylation, and non-coding RNA regulation. These mechanisms can modulate the chromatin structure and accessibility, thereby affecting the transcriptional activity of genes. Chromatin is a complex of DNA and proteins that forms the chromosomes in the nucleus of the cell. The chromatin structure can be altered by adding or removing chemical groups to histones (proteins that wrap around DNA) or DNA itself. These chemical groups can either activate or repress gene expression by changing the affinity of transcription factors (proteins that bind to DNA and initiate transcription) or other regulatory molecules. Non-coding RNAs are RNA molecules that do not code for proteins but can regulate gene expression by interacting with DNA, RNA, or proteins. Epigenetic mechanisms provide a link between environmental stimuli and gene expression, and play an important role in various physiological and pathological processes, including drug addiction. Recent studies have shown that epigenetic mechanisms are involved in the regulation of neurotransmitter systems and neural plasticity in response to METH exposure. Neural plasticity is the ability of neurons to change their structure and function in response to experience or injury. Neural plasticity is essential for learning, memory, adaptation, and recovery. The expression of some genes related to METH addiction is altered by epigenetic modifications, such as histone acetylation, methylation, ubiquitination, and non-coding RNA regulation. These epigenetic changes may affect the synaptic function and morphology, neuronal connectivity, and circuitry formation in the brain regions implicated in METH addiction. Moreover, some epigenetic modifications may persist for a long time after METH withdrawal, suggesting that they may contribute to the development and maintenance of METH addiction. In this article, we review the current literature on the epigenetic mechanisms of METH addiction. We will first introduce METH and its pharmacological effects, and then discuss the epigenetic regulation of neurotransmitter systems and neural plasticity by METH. We will focus on the changes of histone, DNA, and RNA during METH addiction, and the possible causes and consequences of their relationship with METH addiction. We will also provide some perspectives on the potential applications of epigenetic interventions for METH addiction treatment.

The research progress in key technologies for dynamic perception of battlefield casualties was reviewed,including unmanned equipment dynamic mapping,dynamic environment semantic segmentation and casualty detection and identification.The discussion also covered the current state of research on casualty dynamic perception equipment in aerial and ground domains.The development trends of key technologies and equipment for dynamic perception of battlefield casualties were pointed out,and references were provided for enhancing the efficacy of battlefield casualty care and improving medical service support capabilities.[Chinese Medical Equipment Journal,2024,45(9):95-108]

Objective To evaluate the effect of delayed cleaning on the cleaning and disinfection quality of gastro-scopes after pre-treatment with different solutions.Methods According to the factorial design table,combination of the pre-treatment cleaning solutions(factor A)(including multi-enzyme cleaning solution[A1],clean water[A2])and delayed cleaning durations(factor B)(including 0 minutes after pre-treatment[B1],30 minutes after pre-treat-ment[B2],1 hour after pre-treatment[B3],and 3 hours after pre-treatment[B4])yielded eight groups(A1B1,A1B2,A1B3,A1B4,A2B1,A2B2,A2B3,A2B4).According to the usage order of gastroscopes,96 gastroscopes used in the digestive endoscopy center of a tertiary first-class hospital from May to September,2023 were randomly assigned to each group by random number table method,with 12 gastroscopes in each group.Specimens were taken at four time points:after pre-treatment,before cleaning,after cleaning,and after disinfection.Due to instant clea-ning,no specimen before cleaning were taken from A1B1 and A2B1 groups,thus only 3 specimens were taken from these two groups each.Four specimens were taken from gastroscopes in the rest groups,resulting in 360 specimens in total.The internal condition of the biopsy cavity was observed through a cavity detector during each delayed cleaning period after pre-treatment,and specimens were taken at the subsequent reprocessing processes of the gas-troscopes.The microbial conditions of the gastroscopes after pre-treatment,before cleaning,after cleaning,and af-ter disinfection were compared.Results After pre-treatment with multi-enzyme cleaning solution and clean water,there was no statistically significant difference in microbiological detection result(P＞0.05).The biopsy cavity re-mained moist during the delayed cleaning period.There was no statistically significant difference in the microbial de-tection results of factors A and B before and after delayed cleaning as well as after disinfection(all P＞0.05).There was no interaction effect between factor A and B.The distribution of bacterial colonies and disinfection qualified rate of gastroscopes after pre-treatment with two cleaning solutions were also not statistically different(both P＞0.05).Conclusion Delayed cleaning for 30 minutes,1 hour,and 3 hours after pre-treatment does not affect the cleaning and disinfection quality of gastroscopes.When clinical demand is urgent,immediate cleaning should be carried out.However,a certain buffering time(no longer than 3 hours)before cleaning is acceptable,when cleaning and disin-fection workload is heavy and timely cleaning cannot be carried out.

At present, China's traditional Chinese medicine(TCM) industry is developing rapidly with the support of modern science and technology. While promoting economic development and improving national health, it has brought multiple environmental problems. Under the "dual carbon" goals, the ecological fine manufacturing of TCM may become one of the breakthroughs for the TCM industry to practice low-carbon economy. From the perspective of low-carbon economy and considering the current situation of TCM pharmaceutical manufacturing, this paper analyzes the problems and shortcomings of the TCM pharmaceutical industry. In view of the key factors influencing the quality of TCM preparations under the ecological fine manufacturing mode, this paper proposes a practical and feasible selection plan for the ecological fine manufacturing mode of TCM, aiming to provide research ideas and a theoretical basis for the TCM industry in helping to achieve the goals of carbon peaking and carbon neutrality.
Drugs, Chinese Herbal/economics* ; Medicine, Chinese Traditional ; Carbon/analysis* ; China ; Drug Industry/economics*

Aim To explore the inhibitory effect of Buyang Huanwu Decoction on the inflammatory response in the hippocampus of brain tissues of CIRI rats by regulating SIRT1 and the underlying mechanism. Methods The middle cerebral artery embolization (MCAO) model was prepared in rats and divided into sham operation group (Sham), model group (MCAO/R), Buyang Huanwu Decoction group (BYHWT),and BYHWT + SIRT1 inhibitor group (BYHWT + EX527). Zea Longa was used to detect the neurological function score of rats in each group; TTC staining was used to determine the volume of cerebral infarction; HE staining was used to observe the pathological damage of the hippocampus; Western blot was used to detect the expression levels of SIRT1 and IL-6; immunohistochemistry was used to detect TNF-α, IL-1β expression level. Results Compared with the sham group,the neurological function score of the MCAO/R group increased (P < 0.05); the volume of cerebral infarction increased (P < 0.05); the nerve cells in hippocampus were severely damaged, arranged disorderly, and the nucleus was broken; Western blot showed that the expression of SIRT1 decreased, IL-6 expression increased (P <0.05); immunohistochemistry showed that TNF-α,IL-1β expression increased (P < 0.05). Compared with the MCAO/R group, the neurological function score of the BYHWT group decreased (P <0.05); the volume of cerebral infarction decreased (P < 0.05); the damage of nerve cells in hippocampus was reduced; Western blot showed that the expression of SIRT1 increased and IL-6 expression decreased (P < 0.05); immunohistochemistry showed that TNF-α, IL-1β expression decreased (P < 0.05). Compared with the BYHWT group, the neurological function score of the BYHWT + EX527 group increased (P < 0.05); the volume of cerebral infarction was raised (P <0.05); the damage of nerve cells in hippocampus was aggravated; Western blot showed that the expression of SIRT1 decreased and IL-6 expression increased (P < 0.05); immunohistochemistry showed that TNF-α, IL-1β expression increased (P < 0.05). Conclusions Preliminary discussion of Buyang Huanwu Decoction can activate SIRT1 in hippocampus of rat brain tissues to reduce the inflammatory response after CIRI and play a role in brain protection.