Nutritional therapy is a core component of critically ill patient management,and the enteral route has become the preferred method due to its dual roles of nutrition and non-nutrition. The use of vasoactive medications makes enteral nutrition decisions more challenging for these patients. This review systematically examines the pathophysiological effects of vasoactive medications on gastrointestinal tract of critically ill patients,the current value and safety of enteral nutrition in this patient's population,summarizes the optimal strategies for implementing enteral nutrition in these patients for clinical reference.

Objective:To summarize the clinical features of reversible posterior encephalopathy syndrome(PRES)after allogeneic hematopoietic stem cell transplantation(allo-HSCT)in children.Methods:The clinical data of six children who developed PRES after undergoing allo-HSCT in the Department of Hematology of Wuhan Children's Hospital from June 2016 to December 2022 were retrospectively analyzed,and their clinical characteristics,imaging examination,laboratory examination,and treatment regression were summarized.Results:Among 281 children underwent allo-HSCT,6 cases(2.14％)developed PRES,with a median age of 5.1(1.5-9.7)years old.4 cases underwent related haploidentical donor transplantation,and 2 cases underwent sibling allografting and unrelated donor allografting donor transplantation,respectively.All six children had an acute onset of illness,with clinical manifestations of nausea and vomiting,seizures,psychiatric disorders,visual disturbances.The five cases elevated blood pressure.All children with PRES were treated with oral immunosuppressive drugs during seizures,and 3 cases were combined with different degrees of graft-versus-host disease.Most of the children showed effective improvement in clinical symptoms and imaging after adjusting/discontinuing suspected medications(cyclosporine,etc.)and symptomatic supportive treatments(oral antihypertensive,diazepam for antispasmodic,mannitol to lower cranial blood pressure),and one of them relapsed more than 8 months after the first seizure.Conclusion:PRES is rare after hematopoietic stem cell transplantation in children,and its onset may be related to hypertension,cytotoxic drugs,graft-versus-host disease,etc.Most of them can be recovered after active treatment,but not completely reversible,and the prognosis of those who combined with TMA is poor.

This paper aims to investigate the protective effect and mechanism of Astragalus membranaceus and Angelica sinensis before and after compatibility against triptolide(TP)-induced hepatotoxicity. The experiment was divided into a blank group, model group, Astragalus membranaceus group, Angelica sinensis group, and compatibility groups with Astragalus membranaceus/Angelica sinensis ratio of 1∶1, 2∶1, and 5∶1. TP-induced hepatotoxicity model was established, and corresponding drug intervention was carried out. The levels of alanine transaminase(ALT), aspartate transaminase(AST), and alkaline phosphatase(ALP) in serum were detected. Pathological injuries of livers were detected by hematoxylin-eosin(HE) staining. The levels of malondialdehyde(MDA), superoxide dismutase(SOD), glutathione peroxidase(GSH-Px), and reduced glutathione(GSH) in the liver were measured. Wes-tern blot method was used to detect the expression of nuclear factor erythroid 2-related factor 2(Nrf2), Kelch-like ECH-associated protein 1(Keap1), peroxisome proliferator-activated receptor gamma, coactivator-1 alpha(PGC-1α), heme oxygenase-1(HO-1), and NAD(P)H quinone dehydrogenase 1(NQO1) in livers. Immunofluorescence was used to detect the expression of Nrf2 and PGC-1α in livers. The results indicated that Astragalus membranaceus/Angelica sinensis ratio of 2∶1 and 5∶1 could significantly reduce the levels of serum AST, ALT, and ALP, improve the pathological damage of liver tissue, increase the levels of GSH and GSH-Px, and reduce the content of MDA in liver tissue. Astragalus membranaceus/Angelica sinensis ratio of 1∶1 and 2∶1 could significantly improve the level of SOD. Astragalus membranaceus and Angelica sinensis before and after compatibility significantly increased the protein expression of HO-1 and NQO1, improved the protein expression of Nrf2 and PGC-1α, and decreased the protein expression of Keap1 in liver tissue. The above results confirmed that the compatibility of Astragalus membranaceus and Angelica sinensis had antioxidant effects by re-gulating Keap1/Nrf2/PGC-1α, and the Astragalus membranaceus/Angelica sinensis ratio of 2∶1 and 5∶1 had stronger antioxidant effect and significantly reduced TP-induced hepatoto-xicity.
Humans ; Astragalus propinquus ; Angelica sinensis ; NF-E2-Related Factor 2/metabolism* ; Kelch-Like ECH-Associated Protein 1/metabolism* ; Antioxidants/pharmacology* ; Chemical and Drug Induced Liver Injury/prevention & control* ; Superoxide Dismutase/metabolism* ; Oxidative Stress ; Diterpenes ; Epoxy Compounds ; Phenanthrenes

Myocardial infarction (MI) is one of the leading causes of death in the world. With the improvement of clinical therapy, the mortality of acute MI has been significantly reduced. However, as for the long-term impact of MI on cardiac remodeling and cardiac function, there is no effective prevention and treatment measures. Erythropoietin (EPO), a glycoprotein cytokine essential to hematopoiesis, has anti-apoptotic and pro-angiogenetic effects. Studies have shown that EPO plays a protective role in cardiomyocytes in cardiovascular diseases, such as cardiac ischemia injury and heart failure. EPO has been demonstrated to protect ischemic myocardium and improve MI repair by promoting the activation of cardiac progenitor cells (CPCs). This study aimed to investigate whether EPO can promote MI repair by enhancing the activity of stem cell antigen 1 positive stem cells (Sca-1⁺ SCs). Darbepoetin alpha (a long-acting EPO analog, EPO_anlg) was injected into the border zone of MI in adult mice. Infarct size, cardiac remodeling and performance, cardiomyocyte apoptosis and microvessel density were measured. Lin^- Sca-1⁺ SCs were isolated from neonatal and adult mouse hearts by magnetic sorting technology, and were used to identify the colony forming ability and the effect of EPO, respectively. The results showed that, compared to MI alone, EPO_anlg reduced the infarct percentage, cardiomyocyte apoptosis ratio and left ventricular (LV) chamber dilatation, improved cardiac performance, and increased the numbers of coronary microvessels in vivo. In vitro, EPO increased the proliferation, migration and clone formation of Lin^- Sca-1⁺ SCs likely via the EPO receptor and downstream STAT-5/p38 MAPK signaling pathways. These results suggest that EPO participates in the repair process of MI by activating Sca-1⁺ SCs.
Animals ; Mice ; Ventricular Remodeling ; Erythropoietin ; Myocardial Infarction ; Heart ; Stem Cells

Abstract: To analyze the clinical, therapeutic and laboratory characteristics of disseminated cryptococcosis caused by Cryptococcus neoformans invading the blood stream in patient with liver cirrhosis and splenectomy. A 30-year-old male underwent splenectomy plus pericardial devascularization due to "splenomegaly and hypersplenism" in March in 2016. The patient had intermittent fever after operation for many times, and successively accompanied with back pain, left lower limb abscess and right hip pain. The highest body temperature was 39 ℃. CT and MRI revealed the lung lesion and multiple bone destruction. During that period, the effect of antibiotics was not good. On April 19th, 2017, Gram's stain, India ink stain, API 32C, Vitek 2 Compact, ribosomal ITS and IGS sequence analysis were performed to identify the strain isolated from the pus and blood stream. The serum of the patient was detected for cryptococcal antigen. Antifungal susceptibility test was used to determine drug sensitivity and minimum inhibitory concentration (MIC). The Cryptococcus neoformans isolated from fresh pus specimen showed a prominent, thick capsule after India ink stain. The colonies isolated from pus and blood stream were identified Cryptococcus neoformans using API 32C, Vitek 2 Compact, and sequence analysis of rDNA ITS and IGS. Cryptococcal capsule antigen was positive. The minimal inhibitory concentrations of 5-Flucytosine, amphotericin B, fluconazole, itriconazole, voriconazole against the isolate were <4 μg/mL, <0.5 μg/mL, 4 μg/mL, ≤0.25 μg/mL, 0.125 μg/mL respectively. The patient was initially treated with intravenous amphotericin B and flucytosine. After anti-Cryptococcus treatment for two months, the patient clinically improved, and the lesions were reduced on a follow-up CT scan. The patient made a full functional recovery after treatment for six months. Cryptococcosis has hidden onset, atypical clinical symptoms and lack of specificity. Blood stream is the main channel for Cryptococcus to spread and involve many organs of the whole body, including skin, bone and so on. Therefore, early use of blood culture to monitor blood flow dissemination, actively removing the primary focus and cutting off the infection route in time and carrying out effective anti-Cryptococcus treatment are conducive to the patient's early recovery.

The rat everted intestinal sac model was adopted to investigate the absorption of total flavonoids from Coreopsis tinctoria in different intestinal segments. Cyaniding-3-O-β-D-glucoside, chlorogenic acid, flavanomarein, quercetagetin-7-O-β-D-glucoside, iso-okanin, marein and 3,5-dicaffeoylquinic acid which as the major chemical components of total flavonoids from C. tinctoria were selec-ted as the study objects to evaluate the absorption characteristics of each component in different intestinal segments. The results showed that the absorption of seven components of total flavonoids at different intestinal segments was in consistent with zero order absorption rate. The K_a of chlorogenic acid, flavanomarein, quercetagetin-7-O-β-D-glucoside, isookanin and 3,5-dicaffeoylquinic acid increased with increasing of concentration of total flavonoids(P<0.05), indicating that the intestinal absorption of these five components was passive transport. The K_a of cyaniding-3-O-β-D-glucoside and marein showed a weak concentration dependence, suggesting that the absorption of them may be an positive and passive co-existing mode. The result of absorption in different intestinal segments showed that cyaniding-3-O-β-D-glucoside, chlorogenic acid, flavanomarein, quercetagetin-7-O-β-D-glucoside, marein and 3,5-dicaffeoylquinic acid were mainly absorbed in ileum, while isookanin was mainly absorbed in jejunum. The total flavonoids of C. tinctoria are selectively absorbed in intestinal tract, the rat everted intestinal sac model can be used to evaluate the multi-component intestinal absorption characteristics of total flavonoids from C. tinctoria.
Animals ; Chlorogenic Acid ; Coreopsis ; Flavonoids ; Intestinal Absorption ; Plant Extracts ; Rats

Suppression of cellular O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) can repress prolifera-tion and migration of various cancer cells,which opens a new avenue for cancer therapy.Based on the regulation of insulin gene transcription,we designed a cell-based fluorescent reporter capable of sensing cellular O-GlcNAcylation in HEK293T cells.The fluorescent reporter mainly consists of a reporter (green fluorescent protein (GFP)),an internal reference (red fluorescent protein),and an operator (neuronal differentiation 1),which serves as a "sweet switch" to control GFP expression in response to cellular O-GlcNAcylation changes.The fluorescent reporter can efficiently sense reduced levels of cellular O-GlcNAcylation in several cell lines.Using the fluorescent reporter,we screened 120 natural products and obtained one compound,sesamin,which could markedly inhibit protein O-GlcNAcylation in HeLa and human colorectal carcinoma-116 cells and repress their migration in vitro.Altogether,the present study demonstrated the development of a novel strategy for anti-tumor drug screening,as well as for con-ducting gene transcription studies.

ObjectiveTo assess the screening ability of two new anthropometric indices： a body shape index （ABSI） and body roundness index （BRI） for metabolic associated fatty liver disease （MAFLD） in adults， and to determine the optimal cut-off value. MethodsBased on the valid baseline data collected from March 2018 to October 2019 in Dongguan City， Guangdong Province by South China Cohort （SCC） project， a total of 9 214 adults were included， with physical examination， ultrasound and laboratory tests. MAFLD was diagnosed according to the consensus statement of international experts. Body mass index （BMI）， waist circumference （WC） and waist-height-ratio （WHtR） were used as reference to evaluate the screening ability of ABSI and BRI. Spearman rank test and logistic regression model were used to compare the correlation between each index and MAFLD. The receiver operating characteristic curve （ROC） was used to compare the area under the curve （AUC）. ResultsThe prevalence of MAFLD was 31.41%， which increased linearly across the quartile of each index except ABSI. There was a positive correlation between each index and MAFLD but ABSI was the weakest （r_s=0.069 in males and r_s=0.045 in females） while BRI was stronger （r_s=0.409 in males and r_s=0.413 in females）. A multivariate logistic regression analysis of the presence of MAFLD for the highest quartile vs. the lowest quartile of each anthropometric measure， showed that ABSI had the lowest OR without statistical significance. The OR and 95%CI was 1.09 （0.85， 1.41） in males and 0.90 （0.74， 1.08） in females， respectively. BRI was similar to WHtR， and BMI had the strongest association whose OR and 95%CI was 61.15 （35.12， 106.47） in males and 20.07 （15.24， 26.43） in females， respectively. ABSI had the lowest AUC for MAFLD （0.55 in males and 0.53 in females） and the cut-off value was respectively 0.080 5 in males and 0.078 2 in females. BRI had a higher AUC （0.77 in males and 0.75 in females）， equal to WHtR and similar to WC （0.79 in males and 0.77 in females） but lower than BMI （0.81 in males and 0.79 in females）. The optimal cut-off value for BRI was 4.10 in males and 4.51 in females. BRI also showed a certain screening ability on MAFLD in lean/normal weight population （0.73 in males and 0.69 in females）， patients with diabetes （0.73 in males and 0.71 in females） and subjects with lean/normal weight and metabolic dysfunction （0.60 in males and 0.55 in females）. ConclusionsBRI can effectively identify MAFLD （AUC>0.7） and the optimal cut-off value is 4.10 for males and 4.51 for females， while ABSI performs poorly. Considering the screening on MAFLD in population with different characteristics， BRI shows a potential for use in early screening of MAFLD.

ObjectiveTo assess the screening ability of two new anthropometric indices： a body shape index （ABSI） and body roundness index （BRI） for metabolic associated fatty liver disease （MAFLD） in adults， and to determine the optimal cut-off value. MethodsBased on the valid baseline data collected from March 2018 to October 2019 in Dongguan City， Guangdong Province by South China Cohort （SCC） project， a total of 9 214 adults were included， with physical examination， ultrasound and laboratory tests. MAFLD was diagnosed according to the consensus statement of international experts. Body mass index （BMI）， waist circumference （WC） and waist-height-ratio （WHtR） were used as reference to evaluate the screening ability of ABSI and BRI. Spearman rank test and logistic regression model were used to compare the correlation between each index and MAFLD. The receiver operating characteristic curve （ROC） was used to compare the area under the curve （AUC）. ResultsThe prevalence of MAFLD was 31.41%， which increased linearly across the quartile of each index except ABSI. There was a positive correlation between each index and MAFLD but ABSI was the weakest （r_s=0.069 in males and r_s=0.045 in females） while BRI was stronger （r_s=0.409 in males and r_s=0.413 in females）. A multivariate logistic regression analysis of the presence of MAFLD for the highest quartile vs. the lowest quartile of each anthropometric measure， showed that ABSI had the lowest OR without statistical significance. The OR and 95%CI was 1.09 （0.85， 1.41） in males and 0.90 （0.74， 1.08） in females， respectively. BRI was similar to WHtR， and BMI had the strongest association whose OR and 95%CI was 61.15 （35.12， 106.47） in males and 20.07 （15.24， 26.43） in females， respectively. ABSI had the lowest AUC for MAFLD （0.55 in males and 0.53 in females） and the cut-off value was respectively 0.080 5 in males and 0.078 2 in females. BRI had a higher AUC （0.77 in males and 0.75 in females）， equal to WHtR and similar to WC （0.79 in males and 0.77 in females） but lower than BMI （0.81 in males and 0.79 in females）. The optimal cut-off value for BRI was 4.10 in males and 4.51 in females. BRI also showed a certain screening ability on MAFLD in lean/normal weight population （0.73 in males and 0.69 in females）， patients with diabetes （0.73 in males and 0.71 in females） and subjects with lean/normal weight and metabolic dysfunction （0.60 in males and 0.55 in females）. ConclusionsBRI can effectively identify MAFLD （AUC>0.7） and the optimal cut-off value is 4.10 for males and 4.51 for females， while ABSI performs poorly. Considering the screening on MAFLD in population with different characteristics， BRI shows a potential for use in early screening of MAFLD.

AIM:To investigate the effects of Jiawei-Naotai formula (JWNTF) on ATF4/CHOP/Puma pathway in hippocampal neurons of ovariectomized female rats with cerebral ischemia.METHODS:The female rats were randomly divided into sham group, model group, JWNTF group and positive control group.The rats, expect in the sham group, were ovariectomized.The rats in each group were intragastric administration 11 days after ovariectomy.The rats in sham group and model group were given a gavage of 0.9％Na Cl, while the rats in other groups were administrated by corresponding therapy intragastrically for 3 d.The regional cerebral ischemia model was established by middle cerebral artery occlusion (MCAO) suture method 14 days after ovariectomy.The behaviors of the rats were evaluated 24 h after cerebral ischemia.The mRNA levels of Bax, Bcl-2 and caspase-3 were detected by RT-qPCR, and the protein expression of Bax, Bcl-2, caspase-3, ATF4, CHOP and Puma was determined by Western blot.RESULTS:Compared with sham group, the neurobehavioral scores significantly increased in other groups (P<0.05).Compared with model group, the neurobehavioral scores were significantly decreased in positive control group and JWNTF group (P<0.05).The protein expression of Bax, caspase-3, ATF4, CHOP and Puma, and the mRNA expression of Bax and caspase-3 in the hippocampus were much higher, and Bcl-2 was lower in model group than those in sham group (P<0.05).JWNTF significantly reduced the protein expression of Bax, caspase-3, ATF4 and CHOP, and the mRNA expression of Puma, Bax and caspase-3, and markedly increased the expression of Bcl-2 at mRNA and protein levels compared with model group.CONCLUSION:The JWNTF protects against brain damage induced by cerebral ischemia, which may be related to inhibitiing the expression of ATF4/CHOP/Puma pathway-related molecules at mRNA and protein levels.