Effect of cuproptosis on acute kidney injury after cardiopulmonary bypass in diabetic patients

BACKGROUND Cardiopulmonary bypass(CPB)is a common procedure in cardiac surgery.CPB is a high-risk factor for acute kidney injury(AKI),and diabetes is also such a factor.Diabetes can lead to copper overload.It is currently unclear whether AKI after CPB in diabetic patients is related to copper overload.AIM To explore whether the occurrence of CPB-AKI in diabetic patients is associated with cuproptosis.METHODS Blood and urine were collected from clinical diabetic and non-diabetic patients before and after CPB.Levels of copper ion,lactate,glucose,heat shock protein-70(HSP-70),and dihydrolipoamide dehydrogenase(DLAT)were determined.A diabetic rat model was established and CPB was performed.The rats were assessed for the development of CPB-AKI,and for the association of AKI with cuproptosis by detecting copper levels,iron-sulfur cluster proteins and observation of mitochondrial structure by electron microscopy.RESULTS CPB resulted in elevations of copper,lactate,HSP-70 and DLAT in blood and urine in both diabetic and nondiabetic patients.CPB was associated with pathologic and mitochondrial damage in the kidneys of diabetic rats.Cuproptosis-related proteins also appeared to be significantly reduced.CONCLUSION CPB-AKI is associated with cuproptosis.Diabetes mellitus is an important factor aggravating CPB-AKI and cuproptosis.

Role of activin A in carbon tetrachloride-induced acute liver injury

AIM: To investigate the expression and role of activin A in a mouse model of acute chemical liver injury. METHODS: Acute liver injury in C57BL/6 male mice was induced by intraperitoneal injection with carbon tetrachloride (CCl4 ) (0.5 mL/kg, body weight) dissolved in olive oil (1:19 v/v). Mice were sacrificed 1, 3, 5 and 7 d after the treatment. The levels of alanine aminotrans-ferase (ALT) and aspartate aminotransferase (AST) in serum were examined and pathological changes of liver observed by hematoxylin and eosin staining to evaluate the liver injury. Activin A protein levels in serum and hepatic tissue homogenate of mice were detected by enzyme-linked immunosorbent assay, and the expres-sion pattern of activin A protein in livers of mice was examined by immunohistochemistry. Activin type Ⅱ A receptor (ActRⅡA) and Smad3 expressions in the liver were analyzed by real-time quantitative reverse transcription-polymerase chain reaction. In order to further investigate the role of activin A, we also utilized activin A blocking experiment by anti-activin A antibody (500 μg/kg, body weight) injection into mouse tail vein. RESULTS: In CCl4-treated mice, serum ALT and AST levels were significantly increased, compared with that in control mice (P<0.01). Furthermore, the serious necrosis was observed around hepatic portal areas in CCl4-treated mice. Simultaneously, activin A levels in serum and hepatic tissue homogenate of mice treated with CCl4 for 1, 3 and 5 d increased significantly, com-pared with that in control mice (P<0.01). Activin A protein expression in hepatocytes not within the ne-crotic area was also upregulated in mice following CCl4 treatment. Not only activin A, but also ActRⅡA and activin signaling molecule Smad3 mRNA expressions in injury liver induced by CCl4 were significantly higher than that in control liver. In addition, levels of serum ALT and AST in CCl4-treated mice were significantly decreased by injection of anti-activin A antibody to block endogenous activin A action, compared with that in CCl4-treated mice by injection of immunoglobulin G instead of anti-activin A antibody (P<0.01), and the severity of liver injury was also reduced remarkably. CONCLUSION: These data show that activin A is in-volved in CCl4-induced acute liver injury. Blocking ac-tivin A actions may be a therapeutic approach for acute liver injury.

An ultra-sensitive and easy-to-use assay for sensing human UGT1A1 activities in biological systems

The human UDP-glucuronosyltransferase 1A1(UGT1A1),one of the most essential conjugative enzymes,is responsible for the metabolism and detoxification of bilirubin and other endogenous substances,as well as many different xenobiotic compounds.Deciphering UGT1A1 relevance to human diseases and characterizing the effects of small molecules on the activities of UGT1A1 requires reliable tools for probing the function of this key enzyme in complex biological matrices.Herein,an easy-to-use assay for highly-selective and sensitive monitoring of UGT1A1 activities in various biological matrices,using liquid chromatography with fluorescence detection(LC-FD),has been developed and validated.The newly developed LC-FD based assay has been confirmed in terms of sensitivity,specificity,precision,quantitative linear range and stability.One of its main advantages is lowering the limits of detection and quantification by about 100-fold in comparison to the previous assay that used the same probe substrate,enabling reliable quantification of lower amounts of active enzyme than any other method.The precision test demonstrated that both intra-and inter-day variations for this assay were less than 5.5%.Furthermore,the newly developed assay has also been successfully used to screen and characterize the regulatory effects of small molecules on the expression level of UGT1A1 in living cells.Ove rall,an easy-to-use LC-FD based assay has been developed for ultra-sensitive UGT1A1 activities measurements in various biological systems,providing an inexpensive and practical approach for exploring the role of UGT1A1 in human diseases,interactions with xenobiotics,and characterization modulatory effects of small molecules on this conjugative enzyme.

Jejunal cavernous lymphangioma manifested as gastrointestinal bleeding with hypogammaglobulinemia in adult: A case report and literature review

BACKGROUND Lymphangioma is a benign lesion that rarely involves the gastrointestinal tract,especially in adults.Small bowel lymphangioma is a rare cause of gastrointestinal bleeding.Here,we report a case of an adult diagnosed with jejunal lymphangioma presenting with melena,anemia and hypogammaglobulinemia.We also summarize and analyze all 23 reported cases from 1961 to 2019,and propose an algorithm for identification and management of small bowel lymphangioma.CASE SUMMARY A case of a 29-year-old woman presented with persistent melena and irondeficiency anemia,accompanied by hypogammaglobulinemia.No lesions were found in the initial workup with esophagogastroduodenoscopy,colonoscopy and computed tomography(CT)enterography.Ultimately,capsule endoscopy and double-balloon enteroscopy revealed a 3 cm×2 cm primary lesion with intensive white lymphatic dilatatory changes and visible fresh blood stains,accompanied by a small satellite lesion.The patient underwent complete surgical resection of these lesions,and histopathological examination confirmed a diagnosis of cavernous lymphangioma of the jejunum.The patient showed no evidence of disease at the time of this report.CONCLUSION We recommend CT,capsule endoscopy and enteroscopy to identify the lesions of lymphangioma.Laparoscopic surgery with histological diagnosis is an ideal curative method.

Value of Chuanjin Qinggan decoction in improving the depressive state of patients with herpes zoster combined with depression

BACKGROUND Western medicine is beneficial for the recovery of neurological function in patients with depression,but some patients experience side effects such as headaches,dizziness,nausea,gastrointestinal symptoms,insomnia,and cardiac dysfunction.In recent years,integrative medicine has achieved positive results in the treatment of various diseases.AIM To study Chuanjin Qinggan decoction combined with selective serotonin reuptake inhibitors(SSRIs)in patients with herpes zoster complicated by depression.METHODS Patients with herpes zoster complicated by depression who were treated at the Yantai Hospital of Traditional Chinese Medicine from January 2021 to December 2022 were retrospectively selected as research participants.Among them,43 patients with herpes zoster complicated by depression who received SSRI treatment between January and December 2021 were assigned to the Western medicine group,while those who received combined treatment of traditional Chinese and Western medicine between January and December 2022 were assigned to the combined group.Both groups were treated for eight weeks.The degree of pain,effect of herpes zoster treatment,degree of improvement in depressive symptoms,serum neurotransmitter levels,sleep quality,and occurrence of adverse reactions were compared between the two groups.RESULTS We found that after eight weeks of drug treatment,the two treatment schemes achieved differing efficacy.In further comparison,we found that,compared with patients treated with SSRIs alone,patients treated with Chuanjin Qinggan decoction combined with SSRIs showed more significant improvement in depression and a greater increase in dopamine and 5-hydroxytryptamine levels after treatment(P<0.05).Patients treated with Chuanjin Qinggan decoction combined with SSRIs also experienced lower pain,better treatment efficacy for herpes zoster,better sleep quality,and a lower incidence of adverse reactions compared to those treated with SSRIs alone(P<0.05).All minor adverse reactions occurring during treatment were resolved after symptomatic treatment.CONCLUSION The treatment scheme of Chuanjin Qinggan decoction combined with SSRIs can improve the psychological state of patients with herpes zoster complicated by depression and alleviate adverse reactions.

Effects of secondary electron emission on plasma characteristics in dual-frequency atmospheric pressure helium discharge by fluid modeling

A one-dimensional(1D) fluid simulation of dual frequency discharge in helium gas at atmospheric pressure is carried out to investigate the role of the secondary electron emission on the surfaces of the electrodes. In the simulation, electrons,ions of He^+ and He_2^+, metastable atoms of He*and metastable molecules of He*_2 are included. It is found that the secondary electron emission coefficient significantly influences plasma density and electric field as well as electron heating mechanisms and ionization rate. The particle densities increase with increasing SEE coefficient from 0 to 0.3 as well as the sheath's electric field and electron source. Moreover, the SEE coefficient also influences the electron heating mechanism and electron power dissipation in the plasma and both of them increase with increasing SEE coefficient within the range from 0 to 0.3 as a result of increasing of electron density.

Carboxylesterases mediated herb-drug interactions:a systematic review

Esterases participate in the metabolism of^10%of the clinical drugs that contain ester or amide bonds,but the esterases mediated drug/herb-drug interactions(DDIs or HDIs)have not been reviewed in depth.Carboxylesterases(CEs),the most abundant esterases expressed in the metabolic organ of mammals,play a pivotal role in hydrolysis of a variety of endogenous and xenobiotic esters.In the human body,two predominant carboxylesterases including hCE1 and hCE2 have been identified and extensively studied over the past decade.These two enzymes have been found with hydrolytic activity towards a variety of endogenous esters and ester-containing drugs.Recent studies have demonstrated that strong inhibition on hCEs may slow down the hydrolysis of CEs substrates,which may affect their pharmacokinetic properties and thus trigger potential DDIs or HDIs.Over the past decade,many herbal extracts and herbal constitutes have been found with strong inhibitory effects against CEs,and their potential risks on herb-drug interactions(HDIs)have also attracted much attention.This review focused on recent progress in hCEs mediated herb-drug interactions.The roles of hCEs in drug metabolism,the inhibitory capacities and inhibition mechanism of a variety of herbal extract and herbal constitutes against hCEs have been well summarized.Furthermore,the challenges and future perspectives in this field are highlighted by the authors.All information and knowledge presented in this review will be very helpful for the pharmacologists to deeper understand the metabolic interactions between herbal constituents and hCEs,as well as for clinical clinicians to reasonable use herbal medicines for alleviating hCEs-associated drug toxicity or avoiding the occurrence of clinically relevant hCEs-mediated HDIs.

Male external genitalia growth curves and charts for children and adolescents aged 0 to 17 years in Chongqing, China

Genital size is a crucial index for the assessment of male sexual development, as abnormal penile or testicular size may be the earliest visible clinical manifestation of some diseases. However, there is a lack of data regarding penile and testicular size measurements for Chinese boys at all stages of childhood and puberty. This cross-sectional study aimed to develop appropriate growth curves and charts for male external genitalia among children and adolescents aged 0-17 years in Chongqing, China. A total of 2974 boys were enrolled in the present study. Penile length was measured using a rigid ruler, penile diameter was measured using a pachymeter, and testicular volume was determined using a Prader orchidometer. Age-specific percentile curves for penile length, penile diameter, and testicular volume were drawn using the generalized additive models for location, scale, and shape. Very similar growth curves were found for both penile length and penile diameter. Both of them gradually rose to 10 years of age and then sharply increased from 11 to 15 years of age. However, testicular volume changed little before the age of 10 years. This study contributes to the literature covering age-specific growth curve and charts about male external genitalia in Chinese children and adolescents. These age-related values are valuable in evaluating the growth and development status of male external genitalia and could be helpful in diagnosing genital disorders.

On modeling of electrical cyber-physical systems considering cyber security

This paper establishes a new framework for modeling electrical cyber-physical systems(ECPSs),integrating both power grids and communication networks. To model the communication network associated with a power transmission grid, we use a mesh network that considers the features of power transmission grids such as high-voltage levels, long-transmission distances, and equal importance of each node. Moreover, bidirectional links including data uploading channels and command downloading channels are assumed to connect every node in the communication network and a corresponding physical node in the transmission grid. Based on this model,the fragility of an ECPS is analyzed under various cyber attacks including denial-of-service(Do S) attacks, replay attacks, and false data injection attacks. Control strategies such as load shedding and relay protection are also verified using this model against these attacks.