Thrombomodulin reduces α-synuclein generation and ameliorates neuropathology in a mouse model of Parkinson's disease.

The neurotoxic α-synuclein (α-syn) oligomers play an important role in the occurrence and development of Parkinson's disease (PD), but the factors affecting α-syn generation and neurotoxicity remain unclear. We here first found that thrombomodulin (TM) significantly decreased in the plasma of PD patients and brains of A53T α-syn mice, and the increased TM in primary neurons reduced α-syn generation by inhibiting transcription factor p-c-jun production through Erk1/2 signaling pathway. Moreover, TM decreased α-syn neurotoxicity by reducing the levels of oxidative stress and inhibiting PAR1-p53-Bax signaling pathway. In contrast, TM downregulation increased the expression and neurotoxicity of α-syn in primary neurons. When TM plasmids were specifically delivered to neurons in the brains of A53T α-syn mice by adeno-associated virus (AAV), TM significantly reduced α-syn expression and deposition, and ameliorated the neuronal apoptosis, oxidative stress, gliosis and motor deficits in the mouse models, whereas TM knockdown exacerbated these neuropathology and motor dysfunction. Our present findings demonstrate that TM plays a neuroprotective role in PD pathology and symptoms, and it could be a novel therapeutic target in efforts to combat PD. Schematic representation of signaling pathways of TM involved in the expression and neurotoxicity of α-syn. A TM decreased RAGE, and resulting in the lowered production of p-Erk1/2 and p-c-Jun, and finally reduce α-syn generation. α-syn oligomers which formed from monomers increase the expression of p-p38, p53, C-caspase9, C-caspase3 and Bax, decrease the level of Bcl-2, cause mitochondrial damage and lead to oxidative stress, thus inducing neuronal apoptosis. TM can reduce intracellular oxidative stress and inhibit p53-Bax signaling by activating APC and PAR-1. B The binding of α-syn oligomers to TLR4 may induce the expression of IL-1ß, which is subsequently secreted into the extracellular space. This secreted IL-1ß then binds to its receptor, prompting p65 to translocate from the cytoplasm into the nucleus. This translocation downregulates the expression of KLF2, ultimately leading to the suppression of TM expression. By Figdraw.

Mouse serum albumin induces neuronal apoptosis and tauopathies.

The elderly frequently present impaired blood-brain barrier which is closely associated with various neurodegenerative diseases. However, how the albumin, the most abundant protein in the plasma, leaking through the disrupted BBB, contributes to the neuropathology remains poorly understood. We here demonstrated that mouse serum albumin-activated microglia induced astrocytes to A1 phenotype to remarkably increase levels of Elovl1, an astrocytic synthase for very long-chain saturated fatty acids, significantly promoting VLSFAs secretion and causing neuronal lippoapoptosis through endoplasmic reticulum stress response pathway. Moreover, MSA-activated microglia triggered remarkable tau phosphorylation at multiple sites through NLRP3 inflammasome pathway. Intracerebroventricular injection of MSA into the brains of C57BL/6J mice to a similar concentration as in patient brains induced neuronal apoptosis, neuroinflammation, increased tau phosphorylation, and decreased the spatial learning and memory abilities, while Elovl1 knockdown significantly prevented the deleterious effect of MSA. Overall, our study here revealed that MSA induced tau phosphorylation and neuron apoptosis based on MSA-activated microglia and astrocytes, respectively, showing the critical roles of MSA in initiating the occurrence of tauopathies and cognitive decline, and providing potential therapeutic targets for MSA-induced neuropathology in multiple neurodegenerative disorders.

Quercetin-3-O-glc-1-3-rham-1-6-glucoside decreases Aß production, inhibits Aß aggregation and neurotoxicity, and prohibits the production of inflammatory cytokines.

Alzheimer's disease (AD) is a progressive neurodegenerative disease with the hallmark of aggregation of beta-amyloid (Aß) into extracellular fibrillar deposition. Accumulating evidence suggests that soluble toxic Aß oligomers exert diverse roles in neuronal cell death, oxidative stress, neuroinflammation, and the eventual pathogenesis of AD. Aß is derived from the sequential cleavage of amyloid-ß precursor protein (APP) by ß-secretase (BACE1) and γ-secretase. The current effect of single targeting is not ideal for the treatment of AD. Therefore, developing multipotent agents with multiple properties, including anti-Aß generation and anti-Aß aggregation, is attracting more attention for AD treatment. Previous studies indicated that Quercetin was able to attenuate the effects of several pathogenetic factors in AD. Here, we showed that naturally synthesized Quercetin-3-O-glc-1-3-rham-1-6-glucoside (YCC31) could inhibit Aß production by reducing ß-secretase activity. Further investigations indicated that YCC31 could suppress toxic Aß oligomer formation by directly binding to Aß. Moreover, YCC31 could attenuate Aß-mediated neuronal death, ROS and NO production, and pro-inflammatory cytokines release. Taken together, YCC31 targeting multiple pathogenetic factors deserves further investigation for drug development of AD.

Synergistic Glutathione Depletion and STING Activation to Potentiate Dendritic Cell Maturation and Cancer Vaccine Efficacy.

Dendritic cell (DC) maturation and antigen presentation are key factors for successful vaccine-based cancer immunotherapy. This study developed manganese-based layered double hydroxide (Mn-LDH) nanoparticles as a self-adjuvanted vaccine carrier that not only promoted DC maturation through synergistically depleting endogenous glutathione (GSH) and activating STING signaling pathway, but also facilitated the delivery of model antigen ovalbumin (OVA) into lymph nodes and subsequent antigen presentation in DCs. Significant therapeutic-prophylactic efficacy of the OVA-loaded Mn-LDH (OVA/Mn-LDH) nanovaccine was determined by the tumor growth inhibition in the mice bearing B16-OVA tumor. Our results showed that the OVA/Mn-LDH nanoparticles could be a potent delivery system for cancer vaccine development without the need of adjuvant. Therefore, the combination of GSH exhaustion and STING pathway activation might be an advisable approach for promoting DC maturation and antigen presentation, finally improving cancer vaccine efficacy.

Axially chiral styrene-based organocatalysts and their application in asymmetric cascade Michael/cyclization reaction.

An axially chiral styrene-based organocatalyst, featuring a combination of axially chiral styrene-based structure and a pyrrole ring, has been designed and synthesized. This catalyst demonstrates remarkable capabilities in producing a wide range of densely substituted spirooxindoles that feature an alkyne-substituted quaternary stereogenic center. These spirooxindoles are generated through mild cascade Michael/cyclization reactions, resulting in high conversion rates and exceptional enantioselectivity. Our catalytic model, based on experiments, X-ray structure analysis and DFT calculations suggests that chiral matched π-π interactions and multiple H-bonds between the organocatalyst and substrates play significant roles in controlling the stereoselectivity of the reaction.

The unique interplay of mitochondrial oxidative phosphorylation (OXPHOS) and immunity and its potential implication for the sex- and age-related morbidity of severe COVID-19 patients.

Aged male patients are more vulnerable to severe or critical symptoms of COVID-19, but the underlying mechanism remains elusive. In this study, we analyzed previously published scRNA-seq data from a large cohort of COVID-19 patients, castrated and regenerated mice, and bulk RNA-seq of a RNAi library of 400 genes, and revealed that both immunity and OXPHOS displayed cell-type-, sex-, and age-related variation in the severe or critical COVID-19 patients during disease progression, with a more prominent increase in immunity and decrease in OXPHOS in myeloid cells in the males relative to the females (60-69 years old). Male severe or critical patients above 70 years old were an exception in that the compromised negative correlation between OXPHOS and immunity in these patients was associated with its disordered transcriptional regulation. Finally, the expression levels of OXPHOS and androgens were revealed to be positively correlated, and the responses of macrophages to android fluctuation were more striking than other types of detected immune cells in the castrated mice model. Therefore, the interplay of OXPHOS and immunity displayed a cell-type-specific, age-related, and sex-biased pattern, and the underlying potential regulatory role of the hormonal milieu should not be neglected.

ArhGAP11A mediates amyloid-ß generation and neuropathology in an Alzheimer's disease-like mouse model.

Amyloid-ß (Aß) plays an important role in the neuropathology of Alzheimer's disease (AD), but some factors promoting Aß generation and Aß oligomer (Aßo) neurotoxicity remain unclear. We here find that the levels of ArhGAP11A, a Ras homology GTPase-activating protein, significantly increase in patients with AD and amyloid precursor protein (APP)/presenilin-1 (PS1) mice. Reducing the ArhGAP11A level in neurons not only inhibits Aß generation by decreasing the expression of APP, PS1, and ß-secretase (BACE1) through the RhoA/ROCK/Erk signaling pathway but also reduces Aßo neurotoxicity by decreasing the expressions of apoptosis-related p53 target genes. In APP/PS1 mice, specific reduction of the ArhGAP11A level in neurons significantly reduces Aß production and plaque deposition and ameliorates neuronal damage, neuroinflammation, and cognitive deficits. Moreover, Aßos enhance ArhGAP11A expression in neurons by activating E2F1, which thus forms a deleterious cycle. Our results demonstrate that ArhGAP11A may be involved in AD pathogenesis and that decreasing ArhGAP11A expression may be a promising therapeutic strategy for AD treatment.

Fc effector of anti-Aß antibody induces synapse loss and cognitive deficits in Alzheimer's disease-like mouse model.

Passive immunotherapy is one of the most promising interventions for Alzheimer's disease (AD). However, almost all immune-modulating strategies fail in clinical trials with unclear causes although they attenuate neuropathology and cognitive deficits in AD animal models. Here, we showed that Aß-targeting antibodies including their lgG1 and lgG4 subtypes induced microglial engulfment of neuronal synapses by activating CR3 or FcγRIIb via the complex of Aß, antibody, and complement. Notably, anti-Aß antibodies without Fc fragment, or with blockage of CR3 or FcγRIIb, did not exert these adverse effects. Consistently, Aß-targeting antibodies, but not their Fab fragments, significantly induced acute microglial synapse removal and rapidly exacerbated cognitive deficits and neuroinflammation in APP/PS1 mice post-treatment, whereas the memory impairments in mice were gradually rescued thereafter. Since the recovery rate of synapses in humans is much lower than that in mice, our findings may clarify the variances in the preclinical and clinical studies assessing AD immunotherapies. Therefore, Aß-targeting antibodies lack of Fc fragment, or with reduced Fc effector function, may not induce microglial synaptic pruning, providing a safer and more efficient therapeutic alternative for passive immunotherapy for AD.

Effect of moxibustion on plaque psoriasis complicated with obesity / 中国针灸

OBJECTIVE@#To observe the clinical efficacy of moxibustion combined with coptis chinensis ointment sealing on plaque psoriasis complicated with obesity.@*METHODS@#A total of 52 patients of plaque psoriasis complicated with obesity were randomized into an observation group (26 cases) and a control group (26 cases, 2 cases dropped off). Coptis chinensis ointment sealing was adopted in the control group. On the basis of the treatment in the control group, moxibustion was applied at ashi point (area of local target lesions), Zhongwan (CV 12) and bilateral Zusanli (ST 36), Fenglong (ST 40), Quchi (LI 11), Tianshu (ST 25), Shangjuxu (ST 37) in the observation group. The treatment was given 30 min each time, once a day for 4 weeks in both groups. The psoriasis area and severity index (PASI) score, obesity related indexes (body mass, waist circumference, body mass index [BMI]), triglyceride, cholesterol, uric acid and plasma glucose were compared before and after treatment, and the clinical efficacy was evaluated in the two groups.@*RESULTS@#After treatment, the PASI scores were decreased compared with those before treatment in the two groups (P<0.01), and the PASI score in the observation group was lower than that in the control group (P<0.05); the body mass, waist circumference, BMI, triglyceride, cholesterol, uric acid and plasma glucose were decreased compared with those before treatment in the observation group (P<0.01, P<0.05), the triglyceride and cholesterol in the observation group were lower than those in the control group (P<0.05). The total effective rate was 53.8% (14/26) in the observation group, which was superior to 20.8% (5/24) in the control group (P<0.05).@*CONCLUSION@#Moxibustion combined with coptis chinensis ointment sealing can effectively improve the clinical symptoms in patients of plaque psoriasis complicated with obesity.

Analysis of clinical characteristics and risk factors of sarcopenia in elderly patients with chronic kidney disease stage 3-4 / 中华肾脏病杂志

Objective:To explore the clinical characteristics and risk factors of sarcopenia in elderly patients with chronic kidney disease (CKD) stage 3-4.Methods:It was a single-center, retrospective observational study. CKD stage 3-4 patients aged ≥60 years old from March 2019 to March 2022 in the Geriatrics Department of the First Affiliated Hospital of Zhengzhou University were enrolled in the study. General data of the patients were collected, and laboratory indicators, muscle strength, physical function and appendicular muscle mass index (ASMI) were measured. According to the diagnostic criteria of sarcopenia, the patients were divided into no sarcopenia CKD group and sarcopenia CKD group. Baseline data between these two groups were compared. Logistic regression analysis was used to analyze the related factors of sarcopenia in elderly CKD stage 3-4 patients.Results:A total of 162 CKD stage 3-4 patients were enrolled in this study, with 89 males (54.9%) and a median age of 75 (69, 82) years. Sarcopenia was diagnosed in 40 cases, and the prevalence was 24.7% (95% CI 18.1%-31.3%). Compared with no sarcopenia CKD group, age, proportion of dementia, cystatin C, urea nitrogen, C-reactive protein (CRP) and ratio of urine protein to creatinine were higher (all P<0.05), while body mass index (BMI), hemoglobin, carbon dioxide combining power, estimated glomerular filtration rate (eGFR), serum albumin and the proportion of regular exercise and using α-ketones were lower in sarcopenia CKD group (all P<0.05). Meanwhile, grip strength, walking speed, short physical performance battery score and ASMI were lower in sarcopenia CKD group (all P<0.05). Multivariable logistic regression analysis results showed that low eGFR ( OR=0.824, 95% CI 0.687-0.987, P=0.036), low BMI ( OR=0.463, 95% CI 0.304-0.704, P<0.001), low serum albumin ( OR=0.459, 95% CI 0.263-0.802, P=0.006) and high CRP ( OR=2.754, 95% CI 1.708-4.439, P<0.001) were the independent related factors of sarcopenia in elderly CKD patients. Conclusions:The prevalence of sarcopenia in elderly CKD stage 3-4 patients is high. Low eGFR, low BMI, low serum albumin and high CRP are the independent risk factors for sarcopenia in elderly CKD stage 3-4 patients.

Screening and expression analysis of transcription factors involved in genuineness of Codonopsis pilosula in Shanxi / 中国中药杂志

This study aims to mine the transcription factors that affect the genuineness of Codonopsis pilosula in Shanxi based on the transcriptome data of C. pilosula samples collected from Shanxi and Gansu, and then analyze the gene expression patterns, which will provide a theoretical basis for the molecular assisted breeding of C. pilosula. Gene ontology(GO) functional annotation, conserved motif prediction, and gene expression pattern analysis were performed for the differential transcription factors predicted based on the transcriptome data of C. pilosula from different habitats. A total of 61 differentially expressed genes(DEGs) were screened out from the transcriptome data. Most of the DEGs belonged to AP2/ERF-ERF family, with the conserved motif of [2X]-[LG]-[3X]-T-[3X]-[AARAYDRAA]-[3X]-[RG]-[2X]-A-[2X]-[NFP]. Forty-three of the DEGs showed significantly higher gene expression in C. pilosula samples from Shanxi than in the samples from Gansu, including 11 genes in the AP2/ERF-ERF family, 5 genes in the NAC fa-mily, 1 gene in the bHLH family, and 2 genes in the RWP-RK family, while 18 transcription factors showed higher expression levels in the samples from Gansu. GO annotation predicted that most of the DEGs were enriched in GO terms related to transcriptional binding activity(103), metabolic process(26), and stress response(23). The expression of transcription factor genes, CpNAC92, CpNAC100, CpbHLH128, and CpRAP2-7 was higher in the samples from Shanxi and in the roots of C. pilosula. CpNAC92, CpbHLH128, and CpRAP2-7 responded to the low temperature, temperature difference, and iron stresses, while CpNAC100 only responded to low temperature and iron stresses. The screening and expression analysis of the specific transcription factors CpNAC92, CpNAC100, CpbHLH128, and CpRAP2-7 in C. pilosula in Shanxi laid a theoretical foundation for further research on the mechanism of genuineness formation of C. pilosula.

Intelligent diagnostic model of keratoconus based on deep learning algorithm / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To establish an intelligent diagnostic model of keratoconus for small-diameter corneas by data mining and analysis of patients' clinical data.METHODS: Diagnostic study. A total of 830 patients(830 eyes)were collected, including 338 male(338 eyes)and 492 female(492 eyes), with an average age of 14-36(23.19±5.71)years. Among them, 731 patients(731 eyes)had undergone corneal refractive surgery at Chongqing Nanping Aier Eye Hospital from January 2020 to March 2022, and 99 patients had a diagnosed keratoconus from January 2015 to March 2022. Corneal diameter ≤11.1 mm was measured by Pentacam in all patients. Two cornea specialists classified patients' data into normal corneas, suspect keratoconus, and keratoconus groups based on the Belin/Ambrósio enhanced ectasia display(BAD)system in Pentacam. The data of 665 patients were randomly selected as the training set and the other 165 patients as the validation set by computer random sampling method. Seven parametric corneal features were extracted by convolutional neural networks(CNN), and the models were built by Residual Network(ResNet), Vision Transformer(ViT), and CNN+Transformer, respectively. The diagnostic accuracy of models was verified by cross-entropy loss and cross-validation method. In addition, sensitivity and specificity were evaluated using receiver operating characteristic curve.RESULTS: The accuracy of ResNet, ViT, and CNN+Transfermer for the diagnosis of normal cornea and suspect keratoconus was 85.57%, 86.11%, and 86.54% respectively, and the area under the receiver operating characteristic curve(AUC)was 0.823, 0.830 and 0.842 respectively. The accuracy of models for the diagnosis of suspect keratoconus and keratoconus was 97.22%, 95.83%, and 98.61%, respectively, and the AUC was 0.951, 0.939, and 0.988 respectively.CONCLUSION: For corneas ≤11.1 mm in diameter, the data model established by CNN+Transformer has a high accuracy rate for classifying keratoconus, which provides real and effective guidance for early screening.

Effects of heat exposure and vitamin C intervention on oxidative stress and blood pressure changes in treadmill rats / 中华劳动卫生职业病杂志

Objective: To investigate the effect of oxidative stress caused by heat exposure on the blood pressure increase of treadmill rats and the intervention of antioxidants. Methods: In June 2021, Twenty-four healthy SD male rats were randomly divided into four groups: normal temperature feeding, normal temperature treadmill, high temperature treadmill and high temperature treadmill supplementation with vitamin C groups, 6 rats in each group. The rats run on the platform in normal temperature or heat exposure environment for 30 min in the morning and in the afternoon daily, 6 days per week. The daily vitamin C supplement dose of high temperature treadmill supplementation with vitamin C group was 10 mg/kg. BP recordings were done at the end of the week. The rat vascular lipofuscin (LF) was detected by ELISA, the rat serum nitric oxide (NO) was detected by nitrate reductase method, the serum malondialdehyde (MDA) was detected by thibabituric acid method, the serum glutathione peroxidase (GPx) and superoxide dismutase (SOD) were detected by chemiluminescence method, and the serum catalase (CAT) was detected by ammonium molybdate method. The total antioxidant capacity (T-AOC) of serum was measured by iron reduction/antioxidant capacity method, and the content of nuclear erythroid 2-related factor 2 (Nrf2) in vascular tissue was measured by Western blot. The intra-group mean was compared by repeated measurement analysis of variance, and the inter-group mean was compared by single-factor analysis of variance and post-event LSD-t test. Results: Compared with the previous time point, the systolic BP and diastolic BP of the high temperature treadmill group were significantly increased at 7, 14 and 21 d, and decreased at 28 d which were higher than the initial level (P<0.05), and the systolic BP and diastolic BP values at each experimental time point were significantly higher than those of normal temperature treadmill group (P<0.001). The changes of thickening of the artery wall, no smoothing of the endodermis and irregular arrangement of muscle cells in high temperature treadmill group were observed. Compared with the normal temperature treadmill group, the content of MDA in serum, and LF in vascular tissue were significantly increased, the activities of SOD, CAT, T-AOC, the content of NO in serum, and the expression of Nrf2 in vascular tissue were significantly decreased in high temperature treadmill group (P<0.05). Compared with the high temperature treadmill group, the systolic BP and diastolic BP values at 7, 14, 21 and 28 d, the content of serum MDA and LF in vascular tissue were significantly decreased, the activities of CAT and T-AOC, and the expression of Nrf2 in vascular tissue significantly increased (P<0.05), the histopathological changes of the artery wall improved in high temperature treadmill supplementation with vitamin C group. Conclusion: Heat exposure has effect on oxidative stress, which may be related to the increase of BP. Vitamin C as an anti-oxidative enhancer can prevent those negative effects, which could alleviate the pathological changes of vessel intima in heat-exposed rats. And the Nrf2 may be a regulated factor to vascular protection.

Long non-coding RNA SNHG16 promotes human placenta-derived mesenchymal stem cell proliferation capacity through the PI3K/AKT pathway under hypoxia.

BACKGROUND: The effect of hypoxia on mesenchymal stem cells (MSCs) is an emerging topic in MSC biology. Although long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) are reported to play a critical role in regulating the biological characteristics of MSCs, their specific expression and co-expression profiles in human placenta-derived MSCs (hP-MSCs) under hypoxia and the underlying mech anisms of lncRNAs in hP-MSC biology are unknown. AIM: To reveal the specific expression profiles of lncRNAs in hP-MSCs under hypoxia and initially explored the possible mechanism of lncRNAs on hP-MSC biology. METHODS: Here, we used a multigas incubator (92.5% N2, 5% CO2, and 2.5% O2) to mimic the hypoxia condition and observed that hypoxic culture significantly promoted the proliferation potential of hP-MSCs. RNA sequencing technology was applied to identify the exact expression profiles of lncRNAs and mRNAs under hypoxia. RESULTS: We identified 289 differentially expressed lncRNAs and 240 differentially expressed mRNAs between the hypoxia and normoxia groups. Among them, the lncRNA SNHG16 was upregulated under hypoxia, which was also validated by reverse transcription-polymerase chain reaction. SNHG16 was confirmed to affect hP-MSC proliferation rates using a SNHG16 knockdown model. SNHG16 overexpression could significantly enhance the proliferation capacity of hP-MSCs, activate the PI3K/AKT pathway, and upregulate the expression of cell cycle-related proteins. CONCLUSION: Our results revealed the specific expression characteristics of lncRNAs and mRNAs in hypoxia-cultured hP-MSCs and that lncRNA SNHG16 can promote hP-MSC proliferation through the PI3K/AKT pathway.

Influence of pecking frequency at working length on the volume of apically extruded debris: A micro-computed tomography analysis.

Background/purpose: There is no consensus to date on how many repetitive pecking motions at working length (WL) should be regarded as optimal during instrumentation. Therefore, this study aimed to evaluate the effect of pecking frequency at WL on the volume of apically extruded debris using three single-file systems in curved, oval-shaped canals. Materials and methods: Forty-five single-rooted mandibular premolars with curved, oval-shaped canals were prescanned by micro-computed tomography, anatomically paired-matched, and randomly divided among three groups (n = 15 each): Reciproc Blue (RB), WaveOne Gold (WOG) and XP-endo Shaper (XPS). Samples were embedded in agarose gel to collect extruded debris. After preparation to the WL, each sample was rescanned after one, two, four, 10, and 20 pecking motions at WL, respectively. The debris volume was innovatively calculated by a modification of an existing method using micro-computed tomography. The apical preparation size was also measured. Data were compared using a two-way repeated-measures analysis of variance. Results: All single-file systems extruded debris apically, irrespective of the pecking frequency at WL. The extruded debris volume correlated positively with the minor foramen size (P < 0.05); both increased with pecking frequency for each single-file system (P < 0.05). The minor foramen size corresponded to the instrument tip size when reaching the WL once. Conclusion: To produce less debris extrusion and obtain a predictable foramen size corresponding to the instrument tip size, a single pecking motion may be preferred when using single-file systems. Caution should be exercised when applying the current results to clinical situations.

The effect of improving moderate and severe benign prostatic hyperplasia with lower urinary tract symptoms on renal function in elderly patients aged 80 years and over / 中华老年医学杂志

Objective:To investigate the effect of improving moderate and severe benign prostatic hyperplasia(BPH)with lower urinary tract symptoms(LUTS)on renal function in elderly patients aged 80 years and over.Methods:A total of 129 inpatients with moderate and severe BPH and its associated LUTS(BPH/LUTS)who took tamsulosin combined with finasteride aged 80 years old and over in Geriatric Department of the First Affiliated Hospital of Zhengzhou University were enrolled in the retrospective study from July 2018 to July 2020.Patients were divided into normal blood pressure group(n=51)and hypertension group(n=78)and divided into normal renal function group(n=77)and CKD3a stage group(n=52).Serum creatinine, estimated glomerular filtration rate(eGFR), prostate volume(PV)and post-void residual urine volume(PVR), and International Prostate Symptom Score(IPSS)were compared before versus after 1, 3 and 6 months of treatment.Multivariable linear regression analysis was performed to evaluate the influence of the most relevant factors on renal function in patients with BPH/LUTS.Results:After 1, 3 and 6 months of tamsulosin combined with finastide treatment, the lower urinary tract symptoms of elderly patients with BPH/LUTS were improved, IPSS score and PVR were decreased, and the differences were statistically significant(all P<0.01).PV, serum creatinine and eGFR were not changed after 6 months of treatment(all P>0.05).However, further subgroup analysis showed that serum creatinine level in hypertension group and CKD3a stage group was increased compared with that before treatment, while eGFR in CKD3a stage group was decreased before treatment, and the difference was statistically significant(all P<0.05).Compared with before treatment, serum creatinine and eGFR in hypertensive group improved after 3 months of treatment, and CKD3a group improved after 1 month of treatment, and the differences were statistically significant(all P<0.05).There were no significant changes in serum creatinine and eGFR in normal blood pressure group and normal renal function group after 6 months of treatment(all P>0.05).Multiple linear regression analysis showed that hypertension( β=2.06, P<0.05)and CKD3a stage( β=17.16, P<0.01)were independent risk factors for creatinine changes before and after treatment.Hypertension( β=-2.27, P<0.01), CKD3a stage( β=-11.93, P<0.01)and CKD3A stage( β=-2.27, P<0.01)were independent risk factors for creatinine changes before and after treatment. P<0.01)and PV before treatment( β=-0.11, P<0.05)were independent risk factors for the change of eGFR before and after treatment. Conclusions:Treatment for moderate and severe BPH/LUTS can improve renal function in elderly patients with hypertension or CKD3a.

Differences in microbiology and bacterial susceptibility between alcohol abuse and no alcohol abuse in intensive care unit patients / 中国综合临床

Objective:To investigate the differences in microbiological examination results between alcohol abuse and no alcohol abuse in adult ICU patients and the association between alcohol abuse and these differences.Methods:The adult patients with microbiological examination results were selected from the MIMIC-Ⅲ database and divided into two groups according to whether they had alcohol abuse. The two groups were matched by propensity score, and the similarities and differences in microbiological examination results were evaluated between the two groups after matching. The measurement data of non normal distribution were expressed by M ( Q1, Q3). Wilcoxon rank sum test was used for the comparison of the two groups, and the comparison of counting data was used χ 2 test or Fisher exact probability method. Results:After matching, the alcohol abuse patients were more likely to use mechanical ventilation (47.06% (1 379/2 930) vs. 52.66% (1 543/2 930), χ 2=18.14, P<0.001), had a higher positive rate in sputum samples (44.30% (400/903) vs. 49.41% (501/1 014), χ 2=4.81, P=0.028) and had a lower positive rate in other samples (26.85% (653/2 432) vs. 21.67% (541/2 496), χ 2=17.69, P<0.001). In blood samples, the percentage of Gram-negative bacteria was lower in the alcohol abuse group (26.87% (126/469) vs. 17.25% (74/429), χ 2=11.42, P<0.001), while the percentage of Gram-positive bacteria was higher (78.46% (368/469) vs. 86.01% (369/429), χ 2=8.17, P=0.004). The percentage of patients with Pseudomonas aeruginosa (3.75% (110/2 930) vs. 2.08% (61/2 930), χ 2=13.88, P<0.001) and Enterococcus sp. (8.19% (240/2 930) vs. 6.45% (189/2 930), χ 2=6.29, P=0.012) was lower in the alcohol abuse group. However, there was a higher percentage of patients with methicillin-resistant Staphylococcus aureus (2.32% (68/2 930) vs. 3.28% (96/2 930), χ 2=4.57, P=0.032) and Haemophilus influenzae (1.30% (38/2 930) vs. 2.01% (59/2930), χ 2=4.19, P=0.041) in the alcohol abuse group. For Staphylococcus aureus (61.10% (322/527) and 52.66% (267/507), χ 2=7.16, P=0.007) and Enterococcus sp. (75.83% (160/211) and 63.64% (56/88), χ 2=4.02, P=0.045), the alcohol abuse group had a lower resistance to levofloxacin; for Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae, the alcohol abuse group had a lower resistance to cephalosporins (all P<0.05). Conclusions:In adult ICU, alcohol abuse might increase the risks of using mechanical ventilation, and patients with alcohol abuse might be more prone to have respiratory tract infections. Alcohol abuse patients with blood infections were less likely to be infected with Gram-negative bacteria, but had a higher probability of Gram-positive bacteria infection. What is more, Alcohol abuse might increase the risks of infections with Haemophilus influenzae and methicillin-resistant Staphylococcus aureus. In alcohol abuse patients, the infection of Staphylococcus aureus, Enterococcus sp., Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae was less resistant to many antibiotics than that in no alcohol abuse patients.

The effect of store-operated calcium entry inhibitor on liver and kidney injury induced by paraquat / 中华急诊医学杂志

Objective:To investigate the effect of SKF96365, store-operated calcium entry (SOCE) inhibitor, on liver and kidney injury induced by paraquat (PQ).Methods:A549 cells were cultured in vitro and divided into the control group (DMSO group, SKF 2 μmol/L group, and SKF 10 μmol/L group) and PQ group (PQ+DMSO group, PQ+SKF 2 μmol/L group, and PQ+SKF 10 μmol/L group). The nuclear factor of activated T cells (NFAT) in A549 cells was detected by luciferase reporter gene technique. The mouse model of PQ poisoning was constructed and divided into the control group, SKF group, PQ group and PQ+SKF group. In the PQ group, mice were injected with 50 mg/kg PQ intraperitoneally; in the SKF group, mice were injected intraperitoneally with 10 mg/kg SKF96365 for 3 days. Mice in the PQ+SKF group received 50 mg/kg intraperitoneal injection of PQ once and 10 mg/kg intraperitoneal injection of SKF96365 daily for 3 days. On the fourth day, the mice were sacrificed, and the liver and kidney tissues were taken. The histopathological changes of liver and kidney tissues were observed by hematoxylin-eosin (H&E) staining, and the apoptosis of liver and kidney tissues was observed by TUNEL staining. One-way analysis of variance was used to compare the mean values of normally distributed measurement data between groups. Comparisons between groups were performed using the least significant difference t-test. Results:The luciferase reporter gene technology showed that NFAT was significantly activated in the PQ group. After pretreatment with SKF96365, NFAT activation decreased sharply in a dose-dependent manner. HE staining showed that the outline structure of liver and kidney tissues in the PQ groups were unclear, cells swelled and a large number of inflammatory cells infiltrated; in the PQ+SKF group, liver cell swelling and inflammatory cell infiltration decreased significantly. TUNEL staining showed that the apoptotic cells in liver and kidney tissues increased in the PQ groups, and the apoptosis decreased remarkably in the PQ+SKF group.Conclusions:SOCE inhibitor SKF96365 can significantly reduce the liver and kidney injury caused by PQ.

Identification and analysis of glycosyltransferase in Codonopsis pilosula from different regions based on transcriptome / 药学学报

Lu Dangshen is the geoherb in Shanxi Province. The content of Codonopsis pilosula polysaccharides (CPP) in Lu Dangshen is more than that in other Codonopsis Radix from other regions. Glycosyltransferase is the key enzyme for the synthesis of bioactive components, such as CPP and tangshenoside I. Based on the transcriptome data of C. pilosula [Codonopsis pilosula (Franch.) Nannf.] from different producing areas, this study carried out functional annotation of GO and KEGG, conservative domain analysis, phylogenetic tree analysis and expression pattern analysis of glycosyltransferase genes in C. pilosula to provides a theoretical basis for exploring the mechanism of genuineness formation in Lu Dangshen. In this study, 98 glycosyltransferase genes were screened and identified, which belonged to GT family 1, GT family 2, GT family 90 and other families. By GO functional annotation, it was found that most of the glycosyltransferase genes had catalytic activity. Analysis of KEGG functional annotation showed that C. pilosula glycosyltransferase was mainly involved in glycan organism and terpenoid and polyketone metabolism. Among them, conserved domain of 42 glycosyltransferase genes in GT family 1 was [X]-W-[2X]-Q-[3X]-[LH]-[5X]-[FLTHCGWNS]-[2X]-E-[4X]-[GVP]-[4X]-P-[4X]-Q-[2X]-[NAK]. Phylogenetic tree analysis based on the glycosyltransferase sequence in Arabidopsis thaliana showed that C. pilosula glycosyltransferases were mainly located in Arabidopsis thaliana UGT73, 72 and 85 branches. Gene expression pattern analysis showed that expression of CpUGT73AH2 was higher in Lu Dangshen than that in Baitiaodang and could respond to drought and low temperature stress. In conclusion, a glycosyltransferase gene CpUGT73AH2, which is involved in the metabolism of terpenoids and polyketides and can respond to environmental stress, was screened from the C. pilosula glycosyltransferase family 1, which was used to further study the role of C. pilosula glycosyltransferase in Lu Dangshen. It laid a theoretical foundation for further study on the role of C. pilosula glycosyltransferase in the formation of Lu Dangshen.

Establishment of a rapid risk assessment system for imported COVID-19 cases / 中华流行病学杂志

Objective: To develop a rapid risk assessment tool for imported COVID-19 cases and provide reference evidences for prevention and control of COVID-19 at ports. Methods: The information about COVID-19 pandemic and control strategies of 12 concerned countries was collected during July to August 2021, and 12 indexes were selected to assess the importation risk of COVID-19 by risk matrix. Results: The risk for imported COVID-19 cases from 12 countries to China was high or extremely high, and the risk from Russia and the USA was highest. Conclusions: The developed rapid risk assessment tool based on the risk matrix method can be used to determine the risk level of countries for imported COVID-19 cases to China at ports, and the risk of imported COVID-19 was high at Beijing port in August 2021.