Study on the antitussive and expectorant activities and mechanism of platycodin D based on metabolomics method / 药学学报

In this paper, the antitussive and expectorant activity of platycodin D (PD) were studied by constructing a mouse cough induced by concentrated ammonia water and a mouse trachea phenol red excretion model. The mechanism of antitussive and expectorant effect of PD was studied by metabolomics. The animal experiment was approved by the Animal Ethics Committee of Jiangxi University of Chinese Medicine (approval number: JZLLSC-20220739). Then mice were randomly divided into the normal, model, positive drug, PD low-dose, PD medium-dose and PD high-dose group. The antitussive and expectorant effects of PD were evaluated using a cough mouse model induced by concentrated ammonia water and a mouse tracheal phenol red excretion model, respectively. UHPLC-LTQ-Orbitrap-MS was used to identify the metabolites of mouse lung tissue, and multivariate statistical analysis method of orthogonal partial least squares discriminant analysis (OPLS-DA) was used for metabolites profile analysis. The differential metabolites were screened by variable projected importance value (VIP) and t-test results. Pathways for enrichment of differentiated metabolites were analyzed using the MetaboAnalyst platform. The comparative method was applied to analyze the differences in mechanisms of PD, Deapio-platycodin D (DPD) and total platycosides fraction. The results showed that PD at different concentrations could significantly prolong (P < 0.05) the incubation period of cough mice induced by ammonia water, reduce the coughs frequency, and significantly increase (P < 0.05) the amount of phenol red excretion in phenol red excretion model mice. PD could regulate 6 metabolic pathways of phenylalanine, tyrosine and tryptophan biosynthesis, linoleic acid metabolism, phenylalanine metabolism, glycerophospholipid metabolism, and tyrosine metabolism to exert antitussive effect. It could also regulate 8 metabolic pathways of linoleic acid metabolism, glyoxylic acid and dicarboxylic acid metabolism, glycerol phospholipid metabolism, citric acid cycle and arachidonic acid metabolism to exert an expectorant effect. However, only linoleic acid metabolism and glycerophospholipid metabolism could be regulated by the PD, total platycosides fraction and DPD, which may be ascribed to the structural difference of the platycosides and the interaction between platycosides and the intestinal microbiota. Functional analysis showed that these metabolic pathways are closely related to the regulatory mechanisms of anti-inflammatory response, immune function regulation, neurotransmitter release, cell signal transduction, energy metabolism and cell apoptosis. This study shows that PD possesses good antitussive and expectorant activities. In addition, the mechanism difference of PD, total platycosides fraction and DPD imply that the apiose in PD and the interaction between PD and intestinal microbiota could exert an important effect on the antitussive and expectorant mechanism of the platycosides.

Characteristics of retinal microcirculation after phacoemulsification and factors affecting visual acuity / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To investigate the changes of retinal microcirculation after phacoemulsification and the influencing factors of visual acuity.METHODS: Retrospective analysis. A total of 264 cataract patients(264 eyes)who underwent phacoemulsification in our hospital from January 2022 to December 2022 were selected as the study objects. Patients were divided into &#x0026;#x003C; 0.3 group(66 eyes)and ≥0.3 group(198 eyes)according to the recovery of best corrected visual acuity(BCVA)at 3 mo after surgery. The changes of retinal microcirculation indexes were compared before and after treatment. Logistic regression and LASSO regression models were used to screen the influencing factors of postoperative BCVA. A nomogram prediction model of postoperative BCVA was constructed and verified. A restricted cubic spline Logistic regression model was established to analyze the dose-response relationship between end-diastolic velocity(EDV), peak systolic velocity(PSV)and the risk of BCVA recovery.RESULTS: At 3 mo postoperatively, EDV and PSV were significantly improved compared with those before treatment, and resistance index(RI)levels were significantly lower than those before treatment(all P&#x0026;#x003C;0.05). Preoperative EDV, PSV, aqueous humor cell grade, fundus lesion grade, advanced age and Emery grade were influencing factors for poor BCVA recovery after phacoemulsification in cataract patients(P&#x0026;#x003C;0.05). The AUC before and after validation of the nomogram model by Bootstrap method were 0.869(95%CI: 0.815-0.903)and 0.866(95%CI: 0.802-0.895), respectively. The sensitivity was 88.36% and 88.27%, and the specificity was 91.82% and 91.78%, respectively. Restricted cubic spline model analysis showed no nonlinear dose-response relationship between EDV and PSV levels and the risk of poor BCVA recovery in either male or female(P&#x0026;#x003E;0.05).CONCLUSION: After phacoemulsification, retinal microcirculation in cataract patients improved significantly. EDV, PSV, aqueous humor cell grade, fundus lesion grade, advanced age and Emery grade are all factors influencing poor BCVA recovery after cataract surgery.

Clinical and genetic characteristics of adrenomyeloneuropathy / 中华神经科杂志

Objective:To summarize and analyze the clinical and genetic characteristics of Chinese patients with adrenomyeloneuropathy (AMN).Methods:Clinical data were collected and analyzed retrospectively on AMN patients who were diagnosed by genetic testing in Shanghai Sixth People′s Hospital, Shanghai Jiao Tong University School of Medicine from May 2008 to August 2022. Clinical characteristics of AMN patients with different types of gene mutations were compared. Loe score was used to evaluate the severity of white matter demyelinating, and the serum levels of very long-chain fatty acids (VLCFA) in patients with or without white matter demyelinating were compared. The motor function of the AMN patients was assessed using the Expanded Disability Status Scale (EDSS), and the association between EDSS scores and the course of disease was analyzed.Results:A total of 23 male patients with onset age of (29.52±9.91) years were included in this study. The first symptom of all patients was abnormal lower extremities, of which 17 patients showed stiffness and weakness in their lower limbs (73.9%, 17/23), and 6 patients showed numbness and pain in both lower limbs (26.1%, 6/23). The occurrence of symptoms was not related to the type of gene mutation. White matter demyelination occurred in 33.3% (7/21) of patients over a disease duration of (7.67±4.46) years. There was no statistically significant difference in serum VLCFA level between the white-matter demyelination group and the non-demyelination group. The EDSS score was positively correlated with the disease duration ( r=0.57, P=0.006). Sixteen ABCD1 gene mutations were found in this study, among which c.5_19delinsTCTCCAGG (p.P2Lfs *12) was reported for the first time. Four probands belonging to different families carried the c.1415_1416del (p.Q472Rfs *83) variant. Conclusions:Lower limb movement disorders and sensory dysfunction are the prominent clinical manifestations in AMN patients, with deterioration of motor function associated with the course of disease. AMN may be converted to cerebral type and VLCFA concentration is not associated with the phenotypic changes. The c.1415_1416del (p.Q472Rfs *83) mutation is a hot spot mutation of the disease.

A case of mitochondrial diabetes mellitus complicated with hypopituitarism and literature review / 中华内分泌代谢杂志

The clinical data of a patient with mitochondrial diabetes mellitus complicated with hypopituitarism were analyzed, the patient′s mitochondrial gene was detected by microarray capture high-throughput sequencing, and the related domestic and foreign literature was reviewed and analyzed. The results showed that the patient had m. 3243 A>G variant on MT-TL1 gene and the clinical features were consistent with mitochondrial diabetes mellitus and hypopituitarism.

Correlation between metabolic syndrome and hyperuricemia in perimenopausal women / 中华内分泌代谢杂志

Objective:To assess the prevalence of metabolic syndrome(MS) and its relationship with hyperuricemia(HUA) in perimenopausal women in Anning city, Yunnan province.Methods:This is a cross-sectional survey. In May 2021, a multi-stage stratified sampling method was used to collect demographics and clinical data [ethnicity, living community, height, weight, waist circumference, blood pressure, fasting plasma glucose, triglycerides(TG), serum uric acid, high density lipoprotein-cholesterol(HDL-C), alanine transaminase(ALT), etc] in a total of 6 721 perimenopausal women aged 45-60 years.Results:A total of 6 721 perimenopausal women were included in this study. The prevalences of MS and HUA were 14.05%(95% CI 13.22%-14.88%) and 6.46%(95% CI 5.88%-7.07%), respectively. The average age, HDL-C, urea, direct bilirubin, and albumin levels in the perimenstrual HUA population were lower than those in the non-HUA population while the levels of TG, ALT, heart rate, body mass index(BMI), and creatinine were higher(all P<0.05). The prevalence of HUA in perimenopausal women with ethnic minorities and family history of chronic diseases was higher than that in Han nationality and without family history of chronic diseases. The prevalence of MS in perimenopausal women was increased with the increase of serum uric acid( Z=-15.313 8, P<0.001). Multivariate logistic regression model showed that HUA was positively correlated with MS( OR=1.526, 95% CI 1.192-1.954) after adjusting for covariates such as BMI and ethnicity, and the incidence of MS in perimenopausal women in HUA group was 1.526 folds higher than that in non-hyperuricemia group. Conclusion:HUA is highly positively correlated with MS in perimenopausal women. The management of uric acid level in perimenopausal women should be strengthened.

Impact of insulin injection induced lipohypertrophy on multidimensional glucose variability in patients with type 1 diabetes mellitus / 中华内分泌代谢杂志

Objective:This study aimed to investigate the effect of lipohypertrophy induced by insulin injection on blood glucose fluctuation in patients with type 1 diabetes mellitus.Methods:A total of 80 patients with type 1 diabetes mellitus were recruited between June 2021 and December 2021 from the First Affiliated Hospital of Nanjing Medical University. And these patients all received insulin injection more than six months. Lipohypertrophy was assessed by ultrasound scanning, and blood glucose fluctuation was evaluated using the flash glucose monitoring system(FGM). Univariate analysis and multivariate linear regression were used to analyze the relationship of lipohypertrophy and and core indicators of blood glucose fluctuation.Results:Compared with patients without lipohypertrophy, patients with lipohypertrophy had higher mean amplitude of glycemic excursions(MAGE), coefficient of variation(CV), mean of daily differences(MODD), standard deviation(SD) of blood glucose, time above range(TAR), and high blood glucose index(HBGI; all P<0.05), while time in range(TIR) of glucose markedly become lower( P<0.01). Moreover, multivariate linear regression analysis showed that lipohypertrophy detected by ultrasound was an independent influencing factor of TIR( β=-9.423, P=0.032), MAGE( β=1.114, P=0.039), CV( β=4.304, P=0.041), MODD( β=0.717, P=0.046) after adjusting for age at diagnosis, duration of insulin injection, fasting C-peptide, and daily dose of insulin per unit weight. Conclusion:Lipohypertrophy increases glycemic variability and imposes negative impact on glycemic control rate in patients type 1 diabetes mellitus.

Effect of remnant cholesterol levels on carotid intima thickness in patients with type 2 diabetes mellitus evaluated by ultra-high frequency ultrasound / 中华超声影像学杂志

Objective:To discuss the effect of remnant cholesterol (RC) levels on carotid intima thickness (CIT) in patients with type 2 diabetes mellitus (T2DM) by ultra-high frequency ultrasound.Methods:A total of 60 patients with T2DM who received treatment in Henan Provincial People′s Hospital from May 2021 to July 2022 were prospectively recruited, and they were divided into a higher RC group (31 cases) and a lower RC group (29 cases) according to the RC levels. Thirty-one age, sex and body mass index(BMI)-matched healthy volunteers were selected as control group. Carotid CIT, carotid media thickness(CMT) and intima-media thickness(CIMT) were measured by 24 MHz ultra-high frequency ultrasound probe. The difference of general clinical data, laboratory indicators and CIMT, CIT, CMT among the three groups were compared, and the influencing factors of CIT in T2DM patients were explored by multivariate regression analysis.Results:①There were no statistical significances in gender, age, BMI, high-density lipoprotein cholesterol (HDL-C) and CMT among the three groups (all P>0.05). There were no statistical significances in duration of diabetes, fasting blood-glucose and glycated haemoglobin between the two subgroups of T2DM (all P>0.05). ②Compared with the control group, CIMT and CIT were thicker in the T2DM group (both P<0.05). ③CIT was thicker in the higher RC group than in the lower RC group ( P<0.05), while the difference of CIMT was not statistically significant the two groups ( P>0.05). ④Multivariate regression analysis showed that RC was the influence factor of CIT in patients with T2DM(β=0.610, P=0.005). Conclusions:CIT is significantly thicker in T2DM patients with higher RC than in those with lower RC, and RC is the influence factor of CIT, which suggests that more attention should be paid to the detection of RC in T2DM patients.

Online pharmaceutical process analysis of Chinese medicine using a miniature mass spectrometer:Extraction of active ingredients as an example / 药物分析学报

The automation of traditional Chinese medicine(TCM)pharmaceuticals has driven the development of process analysis from offline to online.Most of common online process analytical technologies are based on spectroscopy,making the identification and quantification of specific ingredients still a challenge.Herein,we developed a quality control(QC)system for monitoring TCM pharmaceuticals based on paper spray ionization miniature mass spectrometry(mini-MS).It enabled real-time online qualitative and quantitative detection of target ingredients in herbal extracts using mini-MS without chromatographic separation for the first time.Dynamic changes of alkaloids in Aconiti Lateralis Radix Praeparata(Fuzi)during decoction were used as examples,and the scientific principle of Fuzi compatibility was also investigated.Finally,the system was verified to work stably at the hourly level for pilot-scale extraction.This mini-MS based online analytical system is expected to be further developed for QC applications in a wider range of pharmaceutical processes.

Association of Ego-depletion level with glycemic control and quality of life among adolescents with type 1 diabetes / 中国实用护理杂志

Objective:To investigate the ego-depletion level of adolescents with type 1 diabetes mellitus (T1DM) and to explore its association with glycemic control and quality of life.Methods:This was a cross-sectional survey study. A total of 195 adolescents with T1DM were recruited from the First Affiliated Hospital of Nanjing Medical University from March to September 2022 by convenient sampling method. The Self-Regulatory Fatigue Scale (SRF-S) and Short Form of the Chinese version Diabetes Quality of Life for Youth Scale (C-DQOLY-SF) and the general information questionnaire were collected and the glycated hemoglobin (HbA 1c) value was detected. Results:The total score of self-regulatory fatigue for 195 adolescents with T1DM was (42.23 ± 9.94) points, with a scoring rate of 52.79%, which was at a medium level. Pearson correlation analysis showed that the total score of self-regulatory fatigue was positively correlated with HbA1c ( r = 0.25, P<0.01), and negatively correlated with quality of life ( r = -0.61, P<0.01). The hierarchical linear regression results showed that after controlling for demographic sociolagy and disease variables, ego-depletion had a positive predictive effect on HbA1c ( t = 3.69, P<0.01), while ego-depletion had a negative predictive effect on Quality of life ( t = -8.48, P<0.01). Conclusions:Ego-depletion of adolescents with T1DM may affect their blood glucose control and quality of life, which should be noticed by medical workers.

Diquafosol sodium combined with intense pulsed light in the treatment of meibomian gland dysfunction dry eye after corneal refractive surgery / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To observe the therapeutic effect of the diquafosol sodium combined with intense pulsed light(IPL)on meibomian gland dysfunction(MGD)dry eye after refractive surgery.METHODS:A total of 64 patients(128 eyes)with MGD dry eye diagnosed within 6mo after laser corneal refractive surgery in our hospital from March 2021 to December 2021 were selected. They were randomly divided into control group and experimental group. A total of 33 patients(66 eyes)in the control group were treated with sodium hyaluronate combined with IPL, and 31 patients(62 eyes)in the experimental group were treated with diquafosol sodium combined with IPL. Ocular symptom scores were performed before each IPL treatment in both groups to examine non-invasive tear breakup time(NIBUT), tear meniscus height, lipid layer grade of tear film, meibomian gland deletion rate and uncorrected visual acuity.RESULTS:After IPL treatment, ocular symptom scores and meibomian gland deletion rate score of two groups were decreased continuously. NIBUT, tear meniscus height and lipid layer grade of tear film were increased continuously, and there was no significant change in uncorrected visual acuity. NIBUT of patients in the experimental group was better than that in the control group before the third IPL treatment(6.24±0.27s vs. 5.51±0.24s, P=0.046).CONCLUSIONS:Both diquafosol sodium and sodium hyaluronate combined with IPL showed good therapeutic effect on MGD dry eye, but there was no significant difference in the short-term efficacy between the two groups.

Evaluation of students' satisfaction with three teaching modes in the contact lens course by Students' Evaluations of Educational Quality questionnaire / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To determine the students' satisfaction with the three teaching modes in the contact lens course and provide suggestions to improve teaching quality.METHODS: We conducted a survey at Tianjin Medical University in June 2021 using the Students' Evaluations of Educational Quality(SEEQ)questionnaire. We used descriptive statistics to analyze SEEQ items and the One-way ANOVA was used to determine differences in scores among the three modes.RESULTS: Among the 221 valid responses collected, 87(39.4%)respondents were males and 134(60.6%)were females. The total scores were 151.46(12.45), 148.71(13.14), and 147.97(14.56)for offline, online, and blended teaching, respectively, with no significant difference(F=1.10, P=0.33). Students had a longer interaction time with the teacher in offline teaching than in online and blended teaching(P=0.03). The three different teaching modes have no significant difference among genders or academic performance(P=0.33, P=0.91, respectively). Furthermore, 18.1% of students suggested that the amount of experiment time should be increased.CONCLUSION: Students were satisfied with all three teaching modes. However, they had more interaction time with teachers in traditional offline teaching compared with online and blended teaching. More time is needed to increase teachers' online teaching ability.

Excess Oxygen Supply for Different Time Periods Affect Energy Metabolism in Rat Alveolar Epithelial Type Ⅱ Cells / 中国医学科学院学报

Objective To observe the effect of excess oxygen supply for different time periods on the mitochondrial energy metabolism in alveolar epithelial type Ⅱ cells. Methods Rat RLE-6TN cells were assigned into a control group (21% O2 for 4 h) and excess oxygen supply groups (95% O2 for 1,2,3,and 4 h,res-pectively).The content of adenosine triphosphate (ATP),the activity of mitochondrial respiratory chain complex V,and the mitochondrial membrane potential were determined by luciferase assay,micro-assay,and fluorescent probe JC-1,respectively.Real-time fluorescence quantitative PCR was employed to determine the mRNA levels of NADH dehydrogenase subunit 1 (ND1),cytochrome b (Cytb),cytochrome C oxidase subunit I (COXI),and adenosine triphosphatase 6 (ATPase6) in the core subunits of mitochondrial respiratory chain complexes Ⅰ,Ⅲ,Ⅳ,and Ⅴ,respectively. Results Compared with the control group,excess oxygen supply for 1,2,3,and 4 h down-regulated the mRNA levels of ND1 (q=24.800,P<0.001;q=13.650,P<0.001;q=9.869,P<0.001;q=20.700,P<0.001),COXI (q=16.750,P<0.001;q=10.120,P<0.001;q=8.476,P<0.001;q=14.060,P<0.001),and ATPase6 (q=22.770,P<0.001;q=15.540,P<0.001;q=12.870,P<0.001;q=18.160,P<0.001).Moreover,excess oxygen supply for 1 h and 4 h decreased the ATPase activity (q=9.435,P<0.001;q=11.230,P<0.001) and ATP content (q=5.615,P=0.007;q=5.029,P=0.005).The excess oxygen supply for 2 h and 3 h did not cause significant changes in ATPase activity (q=0.156,P=0.914;q=3.197,P=0.116) and ATP content (q=0.859,P=0.557;q=1.273,P=0.652).There was no significant difference in mitochondrial membrane potential among the groups (F=0.303,P=0.869). Conclusion Short-term excess oxygen supply down-regulates the expression of the core subunits of mitochondrial respiratory chain complexes and reduces the activity of ATPase,leading to the energy metabolism disorder of alveolar epithelial type Ⅱ cells.

Ethanol extract of Herpetospermum caudigerum Wall ameliorates psoriasis-like skin inflammation and promotes degradation of keratinocyte-derived ICAM-1 and CXCL9 / 中西医结合学报

OBJECTIVE@#To explore whether the ethanol extract of Herpetospermum caudigerum Wall (EHC), a Xizang medicinal plant traditionally used for treating liver diseases, can improve imiquimod-induced psoriasis-like skin inflammation.@*METHODS@#Immunohistochemistry and immunofluorescence staining were used to determine the effects of topical EHC use in vivo on the skin pathology of imiquimod-induced psoriasis in mice. The protein levels of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and interleukin-17A (IL-17A) in mouse skin samples were examined using immunohistochemical staining. In vitro, IFN-γ-induced HaCaT cells with or without EHC treatment were used to evaluate the expression of keratinocyte-derived intercellular cell adhesion molecule-1 (ICAM-1) and chemokine CXC ligand 9 (CXCL9) using Western blotting and reverse transcription-quantitative polymerase chain reaction. The protein synthesis inhibitor cycloheximide and proteasome inhibitor MG132 were utilized to validate the EHC-mediated mechanism underlying degradation of ICAM-1 and CXCL9.@*RESULTS@#EHC improved inflammation in the imiquimod-induced psoriasis mouse model and reduced the levels of IFN-γ, TNF-α, and IL-17A in psoriatic lesions. Treatment with EHC also suppressed ICAM-1 and CXCL9 in epidermal keratinocytes. Further mechanistic studies revealed that EHC suppressed keratinocyte-derived ICAM-1 and CXCL9 by promoting ubiquitin-proteasome-mediated protein degradation rather than transcriptional repression. Seven primary compounds including ehletianol C, dehydrodiconiferyl alcohol, herpetrione, herpetin, herpetotriol, herpetetrone and herpetetrol were identified from the EHC using ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry.@*CONCLUSION@#Topical application of EHC ameliorates psoriasis-like skin symptoms and improves the inflammation at the lesion sites. Please cite this article as: Zhong Y, Zhang BW, Li JT, Zeng X, Pei JX, Zhang YM, Yang YX, Li FL, Deng Y, Zhao Q. Ethanol extract of Herpetospermum caudigerum Wall ameliorates psoriasis-like skin inflammation and promotes degradation of keratinocyte-derived ICAM-1 and CXCL9. J Integr Med. 2023; 21(6): 584-592.

Xuebijing injection, a Chinese patent medicine, against severe pneumonia: Current research progress and future perspectives / 中西医结合学报

Severe pneumonia is one of the most common infectious diseases and the leading cause of sepsis and septic shock. Preventing infection, balancing the patient's immune status, and anti-coagulation therapy are all important elements in the treatment of severe pneumonia. As multi-target agents, Xuebijing injection (XBJ) has shown unique advantages in targeting complex conditions and saving the lives of patients with severe pneumonia. This review outlines progress in the understanding of XBJ's anti-inflammatory, endotoxin antagonism, and anticoagulation effects. From the hundreds of publications released over the past few years, the key results from representative clinical studies of XBJ in the treatment of severe pneumonia were selected and summarized. XBJ was observed to effectively suppress the release of pro-inflammatory cytokines, counter the effects of endotoxin, and assert an anticoagulation effect in most clinical trials, which are consistent with experimental studies. Collectively, this evidence suggests that XBJ could play an important and expanding role in clinical medicine, especially for sepsis, septic shock and severe pneumonia. Please cite this article as: Zhang M, Zheng R, Liu WJ, Hou JL, Yang YL, Shang HC. Xuebijing injection, a Chinese patent medicine, against severe pneumonia: Current research progress and future perspectives. J Integr Med. 2023; 21(5): 413-422.

Sulforaphane, an NRF2 agonist, alleviates ferroptosis in acute liver failure by regulating HDAC6 activity / 中西医结合学报

OBJECTIVE@#Acute liver failure (ALF) is characterized by severe liver dysfunction, rapid progression and high mortality and is difficult to treat. Studies have found that sulforaphane (SFN), a nuclear factor E2-related factor 2 (NRF2) agonist, has anti-inflammatory, antioxidant and anticancer effects, and has certain protective effects on neurodegenerative diseases, cancer and liver fibrosis. This paper aimed to explore the protective effect of SFN in ALF and it possible mechanisms of action.@*METHODS@#Lipopolysaccharide and D-galactosamine were used to induce liver injury in vitro and in vivo. NRF2 agonist SFN and histone deacetylase 6 (HDAC6) inhibitor ACY1215 were used to observe the protective effect and possible mechanisms of SFN in ALF, respectively. Cell viability, lactate dehydrogenase (LDH), Fe2+, glutathione (GSH) and malondialdehyde (MDA) were detected. The expression of HDAC6, NRF2, glutathione peroxidase 4 (GPX4), acyl-CoA synthetase long-chain family member 4 (ACSL4) and solute carrier family 7 member 11 (SLC7A11) were detected by Western blotting and immunofluorescence.@*RESULTS@#Our results show that NRF2 was activated by SFN. LDH, Fe2+, MDA and ACSL4 were downregulated, while GSH, GPX4 and SLC7A11 were upregulated by SFN in vitro and in vivo, indicating the inhibitory effect of SFN on ferroptosis. Additionally, HDAC6 expression was decreased in the SFN group, indicating that SFN could downregulate the expression of HDAC6 in ALF. After using the HDAC6 inhibitor, ACY1215, SFN further reduced HDAC6 expression and inhibited ferroptosis, indicating that SFN may inhibit ferroptosis by regulating HDAC6 activity.@*CONCLUSION@#SFN has a protective effect on ALF, and the mechanism may include reduction of ferroptosis through the regulation of HDAC6. Please cite this article as: Zhang YQ, Shi CX, Zhang DM, Zhang LY, Wang LW, Gong ZJ. Sulforaphane, an NRF2 agonist, alleviates ferroptosis in acute liver failure by regulating HDAC6 activity. J Integr Med. 2023; 21(5): 464-473.

Single-cell profiling reveals Müller glia coordinate retinal intercellular communication during light/dark adaptation via thyroid hormone signaling

Light adaptation enables the vertebrate visual system to operate over a wide range of ambient illumination. Regulation of phototransduction in photoreceptors is considered a major mechanism underlying light adaptation. However, various types of neurons and glial cells exist in the retina, and whether and how all retinal cells interact to adapt to light/dark conditions at the cellular and molecular levels requires systematic investigation. Therefore, we utilized single-cell RNA sequencing to dissect retinal cell-type-specific transcriptomes during light/dark adaptation in mice. The results demonstrated that, in addition to photoreceptors, other retinal cell types also showed dynamic molecular changes and specifically enriched signaling pathways under light/dark adaptation. Importantly, Müller glial cells (MGs) were identified as hub cells for intercellular interactions, displaying complex cell‒cell communication with other retinal cells. Furthermore, light increased the transcription of the deiodinase Dio2 in MGs, which converted thyroxine (T4) to active triiodothyronine (T3). Subsequently, light increased T3 levels and regulated mitochondrial respiration in retinal cells in response to light conditions. As cones specifically express the thyroid hormone receptor Thrb, they responded to the increase in T3 by adjusting light responsiveness. Loss of the expression of Dio2 specifically in MGs decreased the light responsive ability of cones. These results suggest that retinal cells display global transcriptional changes under light/dark adaptation and that MGs coordinate intercellular communication during light/dark adaptation via thyroid hormone signaling.

Neuronal Histone Methyltransferase EZH2 Regulates Neuronal Morphogenesis, Synaptic Plasticity, and Cognitive Behavior in Mice / 神经科学通报·英文版

The histone methyltransferase enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2)-mediated trimethylation of histone H3 lysine 27 (H3K27me3) regulates neural stem cell proliferation and fate specificity through silencing different gene sets in the central nervous system. Here, we explored the function of EZH2 in early post-mitotic neurons by generating a neuron-specific Ezh2 conditional knockout mouse line. The results showed that a lack of neuronal EZH2 led to delayed neuronal migration, more complex dendritic arborization, and increased dendritic spine density. Transcriptome analysis revealed that neuronal EZH2-regulated genes are related to neuronal morphogenesis. In particular, the gene encoding p21-activated kinase 3 (Pak3) was identified as a target gene suppressed by EZH2 and H3K27me3, and expression of the dominant negative Pak3 reversed Ezh2 knockout-induced higher dendritic spine density. Finally, the lack of neuronal EZH2 resulted in impaired memory behaviors in adult mice. Our results demonstrated that neuronal EZH2 acts to control multiple steps of neuronal morphogenesis during development, and has long-lasting effects on cognitive function in adult mice.

Transthoracic Echocardiography Revealed Inferior Vena Cava and Right Atrial Occupation:Report of One Case / 中国医学科学院学报

One case with ascites and lower limb edema as the initial manifestations was reported.The echocardiography revealed inferior vena cava and right atrial occupation,which combined with increased alpha fetoprotein and imaging examination,suggested liver malignant tumor combined with tumor thrombus of inferior vena cava and right atrium.After targeted therapy combined with immunotherapy,the tumor shrank and alpha fetoprotein decreased significantly,suggesting that the treatment was effective.The median survival time of the patient was 3 months.This patient had a clear history of cirrhosis due to hepatitis B and was clinically diagnosed with advanced liver cancer,which suggested the importance of early liver cancer screening.

Associations between glycated hemoglobin and glucose indicators in adults in areas at different altitude in China / 中华流行病学杂志

Objective: To explore the associations of glycated hemoglobin (HbA1c) with FPG and oral glucose tolerance test 2-hour (OGTT-2 h) in areas at different altitude in China. Methods: Subjects who participated in 2018-2019 China Chronic Disease and Risk Factor Surveillance and had no prior type 2 diabetes diagnosis were included. Subsequently, they were categorized into three groups based on altitude of living area (<2 000, 2 000- and ≥3 000 m). With adjustment for intracluster correlation, multivariable linear regression analysis was performed to evaluate the associations of HbA1c with FPG and OGTT-2 h in the context of HbA1c was normal (<5.7%) or abnormal (≥5.7%). Furthermore, the shape of relationships between HbA1c and glucose indicators was examined using restricted cubic spline. Finally, receiver operating characteristic curve was used to evaluate the diagnostic performance of HbA1c for diabetes. Results: A total of 157 277 subjects were included in the analysis. While FPG and OGTT-2 h levels gradually decreased with increase of altitude, HbA1c level was similar among the three groups. When HbA1c was <5.7%, its association with FPG and OGTT-2 h was weak and no obvious difference was observed among the three groups. When HbA1c was ≥5.7%, the FPG and OGTT-2 h increased by 15.45% (95%CI:14.71%- 16.18%) and 24.54% (95%CI:23.18%-25.91%) respectively per one standard deviation increase in HbA1c in group in area at altitude <2 000 m. However, the FPG and OGTT-2 h increased by 13.08% (95%CI:10.46%-15.76%) and 21.72% (95%CI:16.39%-27.31%), respectively, in group in area at altitude 2 000- m, and increased by 11.41% (95%CI:9.32%-13.53%) and 20.03% (95%CI:15.38%- 24.86%), respectively, in group of altitude ≥3 000 m. The restricted cubic spline indicated that the curve showing the association of HbA1c with FPG and OGTT-2 h was flat when HbA1c was <5.7%, but showed a positive linear relationship when HbA1c was ≥5.7%. The area under curve for detecting diabetes was 0.808 (95%CI:0.803-0.812) in group of altitude <2 000 m and 0.728 (95%CI:0.660-0.796, P=0.022) in group of altitude ≥3 000 m. The relevant optimal cutoff value of HbA1c was 5.7%, with a sensitivity of 65.4% and a specificity of 83.0%, and 6.0%, with a sensitivity of 48.3% and a specificity of 93.7%, respectively. Conclusions: When HbA1c was ≥5.7%, the association between HbA1c and glucose indicators became weaker as the increase of altitude. In the area at altitude ≥3 000 m, it may not be appropriate to use HbA1c in the diagnosis of diabetes.

Analysis of influential factors for potentially inappropriate medication in elderly cancer patients / 中国药房

OBJECTIVE To analyze the influential factors for potentially inappropriate medication （PIM） in elderly cancer patients. METHODS The data of elderly cancer patients hospitalized in a hospital from January to December 2021 were collected. According to the Beers standard of the American Geriatrics Society in 2019 （hereinafter referred to as the “2019 version of Beers standard”） and Criteria for Potentially Inappropriate Drug Use in Chinese Elderly （2017 version） （hereinafter referred to as the “Chinese PIM standard”）， the PIM status of elderly cancer patients was retrospectively analyzed. Multivariate Logistic regression analysis was used to identify influential factors for PIM. RESULTS A total of 293 patients were included in the study. According to the 2019 version of Beers standard， 211 patients （72.01%） had PIM， of which 204 （69.62%） had PIM related to drugs， 6 （2.05%） had PIM related to diseases or symptoms， 46 （15.70%） had PIM that should be used with caution， 32 （10.92%） had PIM with drug-drug interaction that should be avoided， and 11 （3.75%） had PIM based on renal function； the top 5 drugs in the list of incidence were proton pump inhibitors， metoclopramide， the first-generation antihistamines as promethazine， analgesics as ibuprofen and megestrol. According to the Chinese PIM standard， there were 132 patients （45.05%） with PIM， of which 119 （40.61%） had PIM related to drugs， involving 25 drugs （included 7 high-risk drugs and 18 low-risk drugs）， and 24 （8.19%） with PIM in disease status； top 4 drugs in the list of incidence were promethazine， megestrol， ibuprofen and cimetidine. Multivariate Logistic regression analysis showed that compared with patients with hospital stay≤10 days， patients with hospital 20054） stay between 11 and 30 days had a higher risk of PIM [odds ratio （OR）＝8.836 8， 95% confidence interval （CI） （3.217 8， 31.940 9）， P＝0.000 1]； compared with the patients with the 65895198。E-mail：fjman@cmpt.ac.cn number of clinical disease diagnosed≤5， patients with the number of clinical disease diagnosed≥11 had a higher risk of PIM [OR＝10.930 1， 95%CI （3.000 9， 70.922 9）， P＝0.001 8]； compared with surgical treatment， patients receiving antineoplastic drugs had a higher risk of PIM [OR＝2.209 5， 95%CI （1.180 2， 4.176 9）， P＝0.013 6]. CONCLUSIONS Elderly cancer patients have multiple diseases， complicated medication， and a high incidence of PIM. The length of hospital stay （11-30 d）， the number of clinical disease diagnosed （≥11） and anti-tumor drugs are main influential factors for PIM in patients.