Metabolic reprogramming plays a crucial role in the pathogenesis of cardiovascular diseases(CVD).Lactate,a metabolite of glycolysis,is now considered an important cellular signaling molecule involved in regulating various metabolic processes within the microenvironment.Recently discovered lactylation modifications have been found to play significant roles in CVD such as atherosclerosis(As),vascular or valve calcification,myocardial infarction,heart failure(HF),and pulmonary hypertension(PH).This review summarizes the regulatory mechanisms of lactate and lactylation modifications in these CVD,aiming to provide new insights for their precise prevention and treatment strategies.

Metabolic reprogramming plays a crucial role in the pathogenesis of cardiovascular diseases(CVD).Lactate,a metabolite of glycolysis,is now considered an important cellular signaling molecule involved in regulating various metabolic processes within the microenvironment.Recently discovered lactylation modifications have been found to play significant roles in CVD such as atherosclerosis(As),vascular or valve calcification,myocardial infarction,heart failure(HF),and pulmonary hypertension(PH).This review summarizes the regulatory mechanisms of lactate and lactylation modifications in these CVD,aiming to provide new insights for their precise prevention and treatment strategies.

Objective:To investigate the effects of diquat (DQ) on the expression of intestinal pyroptosis-related proteins and tight junction proteins in rats, and to analyze the role of pyroptosis in the intestinal injury of rats with acute DQ poisoning.Methods:A total of 36 Wistar male rats were randomly divided into control group, and 3 hours, 12 hours, 36 hours and 3 days exposure groups, with 6 rats in each group. Each exposure group was given 1/2 median lethal dose (LD50) of 115.5 mg/kg DQ by one-time gavage. The control group was given the same amount of normal saline by gavage. The control group was anesthetized at 3 hours after DQ gavage to take jejunal tissues; each exposure group was anesthetized at 3 hours, 12 hours, 36 hours, and 3 days after DQ gavage to take jejunal tissues, respectively. The general conditions of the rats were recorded. The pathological changes of jejunum tissue were observed by hematoxylin-eosin (HE) staining. The expression of intestinal pyroptosis-related proteins [NOD-like receptor protein 3 (NLRP3), cysteine aspartate-specific protease 1 (caspase-1), Gasdemin D (GSDMD)] in the intestinal tissues was observed by immunohistochemical staining. Western blotting was used to detect the expression of intestinal pyroptosis-related proteins and intestinal tight junction proteins (Occludin and Claudin-1).Results:Light microscopy showed that pathological changes occurred in jejunum tissue at the early stage of exposure (3 hours), and the injury was the most serious in the 12 hours exposure group, with a large number of inflammatory cells infiltrating in the tissue, and the damage was significantly reduced after 3 days exposure. Immunohistochemical results showed that NLRP3, caspase-1 and GSDMD were expressed in the jejunal mucosa of the control group and the exposure groups, and the positive cells in the control group were less expressed with light staining. The expression of the above proteins in the exposed group was increased significantly and the staining was deep. Western blotting results showed that compared with the control group, the expression of NLRP3 protein in jejunum tissues of all groups was increased, with the most significant increase in the 36 hours group (NLRP3/β-actin: 1.47±0.06 vs. 0.43±0.14, P < 0.01). Compared with the control group, the expression of GSDMD protein in the 3 hours, 12 hours and 36 hours exposure groups increased, and the expression of GSDMD protein in the 3 hours and 12 hours exposure groups increased significantly (GSDMD/β-actin: 1.04±0.40, 1.25±0.15 vs. 0.65±0.25, both P < 0.05). The expression of caspase-1 protein was increased in 36 hours exposure group compared with the control group (caspase-1/β-actin: 1.44±0.34 vs. 0.98±0.19, P > 0.05). Compared with the control group, the expression of Occludin and Claudin-1 proteins in each exposure group decreased, and the expression of Occludin proteins was significantly decreased in the 3 hours, 12 hours, and 36 hours exposure groups decreased significantly (Occludin/β-actin: 0.74±0.17, 0.91±0.20, 0.79±0.23 vs. 1.41±0.08, all P < 0.05). Although the protein expression of Claudin-1 decreased in each exposure group, the difference was not statistically significant. Conclusion:The intestinal injury caused by acute DQ poisoning may be related to the activation of pyroptosis pathway of small intestinal cells and the reduction of the density of intercellular junctions.

OBJECTIVE: To observe the toxicokinetic parameters, absorption characteristics and pathomorphological damage in different parts of the gastrointestinal tract of rats poisoned with different doses of diquat (DQ). METHODS: Ninety-six healthy male Wistar rats were randomly divided into a control group (six rats) and low (115.5 mg/kg), medium (231.0 mg/kg) and high (346.5 mg/kg) dose DQ poisoning groups (thirty rats in each dose group), and then the poisoning groups were randomly divided into 5 subgroups according to the time after exposure (15 minutes and 1, 3, 12, 36 hours; six rats in each subgroup). All rats in the exposure groups were given a single dose of DQ by gavage. Rats in the control group was given the same amount of saline by gavage. The general condition of the rats was recorded. Blood was collected from the inner canthus of the eye at 3 time points in each subgroup, and rats were sacrificed after the third blood collection to obtain gastrointestinal specimens. DQ concentrations in plasma and tissues were determined by ultra-high performance liquid chromatography and mass spectrometry (UPHLC-MS), and the toxic concentration-time curves were plotted to calculate the toxicokinetic parameters; the morphological structure of the intestine was observed under light microscopy, and the villi height and crypt depth were determined and the ratio (V/C) was calculated. RESULTS: DQ was detected in the plasma of the rats in the low, medium and high dose groups 5 minutes after exposure. The time to maximum plasma concentration (Tmax) was (0.85±0.22), (0.75±0.25) and (0.25±0.00) hours, respectively. The trend of plasma DQ concentration over time was similar in the three dose groups, but the plasma DQ concentration increased again at 36 hours in the high dose group. In terms of DQ concentration in gastrointestinal tissues, the highest concentrations of DQ were found in the stomach and small intestine from 15 minutes to 1 hour and in the colon at 3 hours. By 36 hours after poisoning, the concentrations of DQ in all parts of the stomach and intestine in the low and medium dose groups had decreased to lower levels. Gastrointestinal tissue (except jejunum) DQ concentrations in the high dose group tended to increase from 12 hours. Higher doses of DQ were still detectable [gastric, duodenal, ileal and colonic DQ concentrations of 6 400.0 (1 232.5), 4 889.0 (6 070.5), 10 300.0 (3 565.0) and 1 835.0 (202.5) mg/kg respectively]. Light microscopic observation of morphological and histopathological changes in the intestine shows that acute damage to the stomach, duodenum and jejunum of rats was observed 15 minutes after each dose of DQ, pathological lesions were observed in the ileum and colon 1 hour after exposure, the most severe gastrointestinal injury occurred at 12 hours, significant reduction in villi height, significant increase in crypt depth and lowest V/C ratio in all segments of the small intestine, damage begins to diminish by 36-hour post-intoxication. At the same time, morphological and histopathological damage to the intestine of rats at all time points increased significantly with increasing doses of the toxin. CONCLUSIONS The absorption of DQ in the digestive tract is rapid, and all segments of the gastrointestinal tract may absorb DQ. The toxicokinetics of DQ-tainted rats at different times and doses have different characteristics. In terms of timing, gastrointestinal damage was seen at 15 minutes after DQ, and began to diminish at 36 hours. In terms of dose, Tmax was advanced with the increase of dose and the peak time was shorter. The damage to the digestive system of DQ is closely related to the dose and retention time of the poison exposure.
Animals ; Male ; Rats ; Diquat/toxicity* ; Gastrointestinal Diseases ; Intestines ; Poisons ; Rats, Wistar ; Toxicokinetics

Objective:To explore the clinical features of acute diquat (DQ) poisoning, and further improve the awareness of acute DQ poisoning.Methods:A retrospective analysis was performed on the clinical data of patients with acute DQ poisoning diagnosed in the emergency department of the Second Hospital of Hebei Medical University from January 1, 2019 to December 31, 2021. The clinical data included age, gender, exposure routes, presence of pesticides (drugs) mixture poisoning, dosage of poison, the time from taking poisoning to admitting in the emergency department, clinical manifestations, laboratory data, treatment, hospital days, prognosis and survival days.Results:The number of cases who firstly complained of acute DQ poisoning in the past three years were 19 cases in 2019, 28 cases in 2020, and 51 cases in 2021. A total of 12 patients were excluded due to being diagnosed paraquat (PQ) poisoning by toxicology detection. Finally, 86 cases of acute DQ poisoning were included, including 80 cases of oral DQ poisoning, 1 case of intramuscular injection, 1 case of binocular contact and 4 cases of dermal exposure. In 80 cases of oral DQ poisoning, there were 70 cases of diquat poisoning alone (42 cases survived, 28 cases died) and 10 cases of pesticide mixture poisoning (6 cases survived, 4 cases died). The time from oral poisoning to admitting in the emergency department was 0.5-96.0 hours, with an average of (8.6±5.8) hours. The time of intramuscular injection poisoning to admitting in the emergency department was 3 hours. The time of dermal exposure to admitting in the emergency department was relatively long, with an average of 66.1 hours. The time from oral simple DQ poisoning to death was 12.0-108.0 hours, and the time from oral mixed DQ poisoning to death was 24.0-576.0 hours. A total of 70 patients with oral diquat poisoning alone presented various degrees of multiple organ injuries. All patients presented gastrointestinal symptoms such as nausea and vomiting. Renal injury and central nervous system injury were the most significant and closely related to the prognosis.Conclusions:Acute oral DQ poisoning can cause to multiple organ injuries, and the clinical manifestations are related to the dose of the poison. In severe cases, acute renal failure and refractory circulatory failure occur within 24 hours after poisoning, and severe central nervous system injury with disturbance of consciousness as the primary manifestation occurs within 36 hours, followed by multiple organ failure until death.

With the rapid developments of science and technology, the diagnosis technology based on nuclear physics and radiotherapy technology are widely used in medicine, but radiation at the same time could have different levels of damage to human body. Therefore, it is of great significance to research and develop drugs that can prevent and treat radiation damage. The research progresses and prospects of radiation-resistant natural products, such as polysaccharides, flavonoids, phenolic acids, saponins and so on, were reviewed in this paper in order to provide a reference for further developments.

Objective:To analyze the effect of chlorpyrifos on the expression of autophagy related proteins in rat hippocampal neurons, and to explore the role of autophagy in central nerve injury caused by acute chlorpyrifos poisoning.Methods:In October 2018, 35 male clean grade SD rats were randomly divided into 7 groups according to the observation time point, namely 0.5 d, 1 d, 2 d, 3 d, 5 d and 7 d groups and the control group, with 5 rats in each group. Each observation group was given 81.5 mg/kg chlorpyrifos by gavage, and the control group was given olive oil by gavage. The general conditions and poisoning symptoms of rats were observed continuously after exposure. The expressions of autophagy related proteins Beclin1, P62/SQSTM1 and LC3 in hippocampus were detected by Western blot. The cell morphology and LC3 expression in brain were observed by immunohistochemical staining.Results:Western blot results showed that compared with the control group, the expression of Beclin1 protein in hippocampal neurons of rats in the 1 d, 2 d, and 3 d groups increased, while the expression of P62/SQSTM1 protein in the 0.5 d, 1 d, and 2 d groups decreased, and the expression of LC3 protein was decreased in the 2 d group, and the differences were statistically significant ( P<0.05) . The results of immunohistochemistry showed that the hippocampal neurons of rats in the 5 d group were arranged disorderly, and some nuclei contours disappeared, especially in the 7 d group. The LC3 protein was expressed in the cytoplasm, and the expression level gradually increased, reaching a peak on the second day. Conclusion:The early activation of autophagy in rats with acute chlorpyrifos poisoning may be involved in chlorpyrifos induced hippocampal neuronal injury.

Objective:To systematic review the clinical efficacy and safety of neoadjuvant chemotherapy and neoadjuvant concurrent chemoradiotherapy for resectable esophageal squamous cell carcinoma.Methods:Literature search was performed from Web of Science, Pubmed, Cochrane Library, Embase, CBM, Wanfang Data, CNKI and Chongqing VIP. The clinical controlled studies of neoadjuvant chemotherapy versus neoadjuvant concurrent chemoradiation in the treatment of resectable esophageal squamous cell carcinoma was searched. Relevant outcome indicators were analyzed by Revman 5.3 statistical software.Results:Nine studies were included, with a total of 1, 369 patients. Compared with the neoadjuvant chemoradiotherapy, the neoadjuvant chemotherapy had lower overall survival rates at 3 and 5 years( OR=0.68, 95% CI: 0.53-0.86, P<0.05; OR=0.51, 95% CI: 0.34-0.77, P<0.05) , lower pathological complete remission rate( OR=0.28, 95% CI: 0.18-0.45, P<0.05)and R0 resection rate( OR=0.39, 95% CI: 0.22-0.68, P<0.05), The total postoperative complication rate is similar( OR=1.07, 95% CI: 0.75-1.51, P>0.05). Conclusion:Neoadjuvant concurrent radiochemotherapy maybe superior to neoadjuvant chemotherapy among patients with resectable esophageal squamous cell carcinoma.

Objective:To evaluate the impact of the reform of the county medical community on the expenditure of medical insurance funds, and to provide references for maintaining the stability of the medical insurance fund and deepening the reform of the medical community.Methods:Medical insurance data of urban and rural residents in M County, Yunnan province from 2016 to 2019 were collected, and a discontinuous time series model was used to analyze the impact of county medical community reform on medical insurance fund expenditures.Results:Since the reform, the number of patients discharged from county-level hospitals has shown a downward trend, averaging a decrease of 25.996 people per month; yet increases have emerged with the average hospitalization expenditure, the average hospitalization overall fund expenditure, and the average outpatient overall fund expenditure, averaging a monthly increase of 90.931 yuan, 50.014 yuan and 1.528 yuan respectively. The average hospitalization expenditure, the average hospitalization overall fund expenditure, and the average outpatient overall fund expenditure of the township hospitals all showed an upward trend, averaging a monthly increase of 31.191 yuan, 38.678 yuan and 0.085 yuan respectively. The flow of external medical insurance funds of the medical community has shown a continuous upward trend, averaging a monthly increase of hospitalization fund expenditures of 33.005 yuan, and a monthly increase of outpatient overall fund expenditures of 4.896 yuan overall.Conclusions:The M County medical community should further strengthen the top-level design, explore the reform of medical insurance payment methods, improve the regional information platform, standardize the referral system, and strengthen supervision to deepen the construction of the medical community to ensure the sustainable operation of medical insurance funds.

Objective:To investigate the current situation of emergency medical service (EMS) system and its effect on treatment of the acute stage and short- and long-term prognosis in patients with acute myocardial infarction in Hebei province.Methods:Totally 2 961 patients with acute myocardial infarction who were admitted to major tertiary and some representative secondary hospitals in Hebei province from January 2016 to December 2016 were collected. According to the pattern of arriving hospital, all the patients were divided into the EMS group and self-transport group. The general conditions, time from onset to treatment, treatment methods, in-hospital mortality rate and 3-year mortality rate were compared between the two groups.Results:Of the included 2 961 patients, 33.13% of them were transported through EMS and 66.87% of them by private transport. Patients with a history of hypertension and ST-segment elevation myocardial infarction were more likely to choose EMS, and the difference was statistically significant ( P<0.05). Moreover, patients in the EMS group were more likely to go to tertiary hospitals for treatment (88.58% vs 85.76%, P=0.033). The time from onset to treatment of the EMS group was significantly shorter than that of the self-transport group (160 min vs 185 min, P<0.01), and the proportion of patients in the EMS group from onset-to-door time in <3 h and 3-6 h was higher than that of the self-transport group (55.76% vs 49.14%, 21.41% vs 19.09%, P<0.01). Compared with the self-transport group, the EMS group has a higher rate of reperfusion therapy (67.48% vs 61.67%, P=0.002). Patients in the EMS group had a higher in-hospital mortality rate in the acute stage (7.03% vs 4.44%, P=0.003), but its 3-year mortality rate was lower than that of the self-transport group (17.31% vs 20.77%, P<0.05). Conclusions:EMS can shorten symptom-onset-to-arrival time, increase the rate of reperfusion therapy and improve long-term prognosis of patients with acute myocardial infarction.