Inhibiting glutamine metabolism has been proposed as a potential treatment strategy for improving non-alcoholic steatohepatitis (NASH). However, effective methods for assessing dynamic metabolic responses during interventions targeting glutaminolysis have not yet emerged. Here, we developed a positron emission tomography (PET) imaging platform using l-[5-¹¹C]glutamine ([¹¹C]Gln) and evaluated its efficacy in NASH mice undergoing metabolic therapy with bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide (BPTES), a glutaminase 1 (GLS1) inhibitor that intervenes in the first and rate-limiting step of glutaminolysis. PET imaging with [¹¹C]Gln effectively delineated the pharmacokinetics of l-glutamine, capturing its temporal-spatial pattern of action within the body. Furthermore, [¹¹C]Gln PET imaging revealed a significant increase in hepatic uptake in methionine and choline deficient (MCD)-fed NASH mice, whereas systemic therapeutic interventions with BPTES reduced the hepatic avidity of [¹¹C]Gln in MCD-fed mice. This reduction in [¹¹C]Gln uptake correlated with a decrease in GLS1 burden and improvements in liver damage, indicating the efficacy of BPTES in mitigating NASH-related metabolic abnormalities. These results suggest that [¹¹C]Gln PET imaging can serve as a noninvasive diagnostic platform for whole-body, real-time tracking of responses of glutaminolysis to GLS1 manipulation in NASH, and it may be a valuable tool for the clinical management of patients with NASH undergoing glutaminolysis-based metabolic therapy.

Objective To investigate the correlation of serum calmodulin(CaM)level with the con-dition and prognosis of patients with severe traumatic brain injury(sTBI).Methods A total of 208 elderly sTBI patients admitted to the Geriatric Hospital and Puren Hospital Affiliated to Wuhan University of Science and Technology from January 2021 to June 2023 were enrolled,and after 3 months'follow-up,192 cases were finally included in this study.According to their progno-sis,they were divided into poor prognosis group(n=56)and good prognosis group(n=136).Their general data were collected,and serum CaM level was measured by ELISA.Pearson correla-tion analysis was used to study the correlation between the level and the disease condition.Multi-variate logistic regression model was employed to screen the prognosis related factors of sTBI pa-tients,and restricted cubic spline was applied to fit the relationship between serum CaM level and prognosis of sTBI patients.Results Midline shift,significantly lower CaM level and acute physi-ology and chronic health evaluation Ⅱ(APACHE Ⅱ)score,and obviously higher Glasgow Coma Scale(GCS)score and albumin level were observed in the good prognosis group than the poor prognosis group(P＜0.05,P＜0.01).Pearson correlation analysis showed that serum CaM level was negatively correlated with condition of sTBI(r=-0.804,P＜0.05).Multivariate logistic analysis indicated that APACHE Ⅱ score(OR=1.248,95％CI:1.076-1.447,P=0.003)and ser-um CaM level(OR=1.030,95％CI:1.017-1.044,P=0.001)were risk factors for prognosis,while,GCS score(OR=0.730,95％CI:0.536-0.994,P=0.045)and serum albumin level(OR=0.730,95％CI:0.649-0.822,P=0.001)were protective factors for poor prognosis in sTBI pa-tients.Restricted cubic spline revealed that there was a linear dose-response relationship between serum CaM level and prognosis of sTBI patients(X2=27.080,P＜0.01).Conclusion Serum CaM level is correlated with sTBI disease and prognosis.

AIM To evaluate the quality of Changmaile Capsules(Ⅰ).METHODS The analysis was performed on a 35℃ thermostatic Thermo Scientific AccucoreTM XL C18 column(4.6 mm×250 mm,4 μm),with the mobile phase comprising of methanol-acetonitrile-0.5% phosphoric acid flowing at 1 mL/min in a gradient elution manner,and the detection wavelengths were set at 230,280 nm.The contents of gastrodin,danshensu,quercetin-3-O-β-D-glucose-7-O-β-D-gentiobioside,3′-hydroxypuerarin,puerarin,3′-methoxypuerarin,puerarin apioside,daidzin,rosmarinic acid,lithospermic acid,ononin,daidzein,salvianolic acid B,calycosin,paeoniflorin and isoquercitrin were determined,after which HPLC fingerprints were established,along with the calculation of similarities.RESULTS Sixteen constituents showed good linear relationships within their own ranges(r≥0.999 0),whose average recoveries were 87.4%-103.9% with the RSDs of 0.54%-3.10% .At 230 nm,the fingerprints of ten batches of samples demonstrated similarities of 0.954-0.999,which displayed obvious differences at 280 nm.3′-Hydroxypuerarin,puerarin,3′-methoxypuerarin,puerarin apioside,daidzin and daidzein were main differential constituents,paeoniflorin and isoquercitrin exhibited stable contents in various batches of samples.CONCLUSION This simple,accurate and reliable method can be used for the quality control of Changmaile Capsules(Ⅰ).

AIM To study the chemical constituents from the stems of Gnetum parvifolium(Warb.)C.Y.Cheng ex Chun and their xanthine oxidase inhibitory activities.METHODS The 95%ethanol extract from the stems of G.parvifolium was isolated and purified by silica gel,MCI and preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The inhibitory activities on xanthine oxidase was determined by ultraviolet spectrophotometry.RESULTS Seventeen compounds were isolated and identified as isorhapontigenin(1),resveratrol(2),4-hydroxybenzaldehyde(3),cycloeucalenol(4),(E)-1-(3',5'-dimethoxyphenyl)-2-(3,4-dimethoxyphenyl)ethene(5),stigmast-4-en-3-one(6),medioresinol(7),chrysin(8),aurantiamide acetate(9),(-)-pinoresinol(10),methyl 4-hydroxybenzoate(11),2-methoxybenzene-1,4-diol(12),gnetumontain C(13),syringaresinol(14),homoeriodictyol(15),vanillin(16),β-sitosterol(17).The IC50 values of compounds 1-3,15-16 were(11.4±0.54),(14.1±1.06),(320.4±0.75),(360.6±0.78),(386.3±0.71)μmol/L,respectively.CONCLUSION Compounds 3-4 are isolated from this plant for the first time.Compounds 5-13 are first isolated from genus Gnetum.Compounds 1-3,15-16 have xanthine oxidase inhibitory activities.

OBJECTIVES: This cohort study investigated the correlation between Parkinson’s disease (PD) risk and chronic obstructive pulmonary disease (COPD) risk under particulate matter with an aerodynamic diameter ≤2.5 μm (PM2.5) exposure. METHODS: Data from the National Health Research Institutes of Taiwan were used in this study. The Environmental Protection Administration of Taiwan established an air quality monitoring network for monitoring Taiwan’s general air quality. COPD was indicated by at least 3 outpatient records and 1 hospitalization for COPD. After the implementation of age, sex, and endpoint matching at a 1:4 ratio, 137 patients and 548 patients were included in the case group and control group, respectively. Based on the 2005 World Health Organization (WHO) standards, monthly air particle concentration data were classified into the following 4 groups in analyses of exposure–response relationships: normal level, and 1.0, 1.5, and 2.0 times the WHO level ([concentration ≥2]×25 μg/m3×number of exposure months). RESULTS: A multivariate logistic regression revealed that the 1.0 and 1.5 WHO level groups did not significantly differ from the normal level group, but the 2.0 WHO level did (odds ratio, 4.091; 95% confidence interval, 1.180 to 14.188; p=0.038). CONCLUSIONS Elevated PM2.5 concentrations were significantly correlated with an increased risk of PD among patients with COPD. Furthermore, exposure to high PM2.5 levels can further increase the risk of PD.

INTRODUCTION: Hospital-at-home programmes are well described in the literature but not in Asia. We describe a home-based inpatient substitutive care programme in Singapore, with clinical and patient-reported outcomes. METHODS: We conducted a retrospective cohort study of patients admitted to a hospital-at-home programme from September 2020 to September 2021. Suitable patients, who otherwise required hospitalisation, were admitted to the programme. They were from inpatient wards, emergency department and community nursing teams in the western part of Singapore, where a multidisciplinary team provided hospital-level care at home. Electronic health record data were extracted from all patients admitted to the programme. Patient satisfaction surveys were conducted post-discharge. RESULTS: A total of 108 patients enrolled. Mean age was 67.9 (standard deviation 16.7) years, and 46% were male. The main diagnoses were skin and soft tissue infections (35%), urinary tract infections (29%) and fluid overload (18%). Median length of stay was 4 (interquartile range 3-7) days. Seven patients were escalated back to the hospital, of whom 2 died after escalation. One patient died at home. There was 1 case of adverse drug reaction and 1 fall at home, and no cases of hospital-acquired infections. Patient satisfaction rates were high and 94% of contactable patients would choose to participate again. CONCLUSION Hospital-at-home programmes appear to be safe and feasible alternatives to inpatient care in Singapore. Further studies are warranted to compare clinical outcomes and cost to conventional inpatient care.
Aftercare ; Aged ; Female ; Hospitalization ; Humans ; Length of Stay ; Male ; Patient Discharge ; Retrospective Studies ; Singapore

Objective:To study the effect of Fushengong prescreption on the regulation-antagonism effect of angiotensin converting enzyme-angiotensin Ⅱ-angiotensin Ⅱ 1 receptor （ACE-AngⅡ-AT1R） axis and angiotensin converting enzyme 2-angiotensin （1-7）-Mas receptor［ACE2-Ang（1-7）-MASR］ axis of rats with chronic renal failure（CRF）， and to explore its mechanism of delaying the development of CRF. Method:The 65 male SD rats were randomly divided into normal group （n=10） and modeling group （n=55）. The normal group was routinely reared， while the modeling group were administered by gavage with 0.25 g·kg^-1d^-1 adenine suspension for 28 days. After the model was successfully established， the survival model rats were randomly divided into model group， benazepril group（0.01 g·kg^-1·d^-1）and low，medium and high dose of Fushengong prescreption groups （4，8，16 g·kg^-1·d^-1）. The normal group and model group were administered the same volume of normal saline by gavage， lasted for 28 days. After the experiment， systolic blood pressure （SBP） and diastolic blood pressure （DBP） of caudal artery were measured， and 24-hour urine was collected to determine 24-hour urine protein （24 h U-pro）. The content of serum creatinine（SCr） and blood urea nitrogen （BUN） in the serum were measured， the histological morphology was observed by hematoxylin eosin（HE）staining， and the degree of renal interstitial fibrosis was observed by Masson staining. Enzyme linked immunosorbent assay （ELISA） was used to determine the contents of AngⅡ， Ang （1-7） and Cystatin C （CysC） in serum and renal homogenate. The protein level of ACE， ACE2， AT1R and MASR were detected by Western blot. The expression of ACE and ACE2 protein in renal tissues were detected by immunohistochemistry. Result:Compared with normal group， the expression levels of SCr， BUN and CysC in model group were significantly increased（P<0.05）， the content of AngⅡ in serum and kidney tissues were significantly increased， the content of Ang （1-7） were significantly decreased（P<0.05）， the expression of ACE and AT1R protein in renal tissues were significantly increased（P<0.05）， and the expression of ACE2 and MASR protein were significantly decreased（P<0.05）. Compared with model group and benazepril group， after the intervention with Fushengong prescreption， the serum SCr，BUN and CysC decreased（P<0.05），the content of AngⅡ in serum and kidney tissues decreased significantly，Ang（1-7） increased significantly（P<0.05）， the expression of ACE and AT1R protein in renal tissues decreased significantly（P<0.05）， ACE2 and MASR protein increased significantly（P<0.05）. The high-dose Fushengong prescreption has the best effect. The high， medium and low-dose effects of Fushengong prescreption were dose-dependent. Conclusion:Fushengong prescreption improved renal function and pathological change of kidney in adenine-induced rats with chronic renal failure. The mechanism may be related to the inhibition of ACE-AngⅡ-AT1R axis and promotion of ACE2-Ang（1-7）-MASR axis ，which leads to the delaying of the progression of chronic renal failure.

Long non-coding RNAs (lncRNAs) regulate transcription to control development and homeostasis in a variety of tissues and organs. However, their roles in the development of the cerebral cortex have not been well elucidated. Here, a bioinformatics pipeline was applied to delineate the dynamic expression and potential cis-regulating effects of mouse lncRNAs using transcriptome data from 8 embryonic time points and sub-regions of the developing cerebral cortex. We further characterized a sense lncRNA, SenZfp536, which is transcribed downstream of and partially overlaps with the protein-coding gene Zfp536. Both SenZfp536 and Zfp536 were predominantly expressed in the proliferative zone of the developing cortex. Zfp536 was cis-regulated by SenZfp536, which facilitates looping between the promoter of Zfp536 and the genomic region that transcribes SenZfp536. Surprisingly, knocking down or activating the expression of SenZfp536 increased or compromised the proliferation of cortical neural progenitor cells (NPCs), respectively. Finally, overexpressing Zfp536 in cortical NPCs reversed the enhanced proliferation of cortical NPCs caused by SenZfp536 knockdown. The study deepens our understanding of how lncRNAs regulate the propagation of cortical NPCs through cis-regulatory mechanisms.

Objective　To explore the relationship between island sign,coagulation function and hematoma enlargement of HICH,and to study their predictive value for hematoma enlargement.Methods　We selected HICH patients in the Department of Neurosurgery of Wuhan Puren Hospital from January 2019 to January 2021 as the research objects.According to whether there is an enlarged hematoma,the patients were divided into an enlarged hematoma group and an unexpanded hematoma group.We compared the baseline data of the two groups and used a multivariate logistics regression analysis method to analyze independent risk factors for hematoma enlargement.We used ROC curve and AUC to analyze and compare the predictive value of island sign and coagulation function for hematoma enlargement of HICH.Results　Whether the hematoma breaks into the ventricle,island sign,GCS score,PT,INR,hematoma volume,blood sugar level is related to hematoma enlargement of HICH (P＜0.05).Among them,the island sign,GCS score,PT,and whether the hematoma breaks into the ventricle are independent risk factors for hematoma enlargement of HICH (P＜0.05).The AUC of island and coagulation function＞AUC of individual island sign and AUC of individual coagulation function (P＜0.05).Conclusion　Compared with the island sign or PT alone,the island sign combined with PT has a better predictive value for hematoma enlargement of HICH.

Objective To characterize the epidermal growth factor receptor (EGFR) gene in Schistosoma japonicum (SjEGFR gene) and investigate the role of the EGFR gene in regulating the growth, reproductive system, maturation and fecundity of S. japonicum. Methods Rapid amplification of cDNA ends (RACE) was performed to obtain the full length of the SjEGFR gene, and the SjEGFR gene expression was quantified in different developmental stages of S. japonicum using a quantitative real-time PCR (qPCR) assay. The tissue localization of the SjEGFR gene was detected in 22-day parasite using whole-mount in situ hybridization (WISH). Following RNA interference (RNAi)-induced knockdown of the SjEGFR gene, the worm length, pairing rate and worm burden of S. japonicum were measured, and the worm morphology was observed using optical microscopy and confocal microscopy. Results The SjEGFR gene was identified with a conserved tyrosine-kinase active site, and the SjEGFR gene expression was detected at various developmental stages in male and female parasites. WISH showed that the transcript of the SjEGFR gene was localized on the tegument and in the digestive organs of S. japonicum. RNAi-induced SjEGFR knockdown resulted in marked suppression of the worm growth, smaller size of male testicles that contained more immature spermatocytes, and apparent impairment of ovary and vitelline gland development. In addition, no eggs were found in the uterus of SjEGFR knocked-down female parasites, indicating the interruption of egg production. Conclusions Inhibition of SjEGFR expression may remarkably suppress the growth and maturation of S. japonicum, and interrupt the egg production.