Development and validation of the head and neck cancer psychosocial distress scale (HNCPDS) to identify patients at high risk for psychological problems : a multicenter study.

To develop the Head and Neck Cancer Psychosocial Distress Scale (HNCPDS) with the aim of identifying high-risk individuals for psychosocial distress among patients, and to assess its reliability, validity and applicability. Using the classical test theory, a total of 435 head and neck cancer patients from six tertiary hospitals in China were recruited for developing the HNCPDS. Delphi expert consultation and item analysis were used to improve the content validity of the preliminary HNCPDS. Factor analysis (FA) and Structural equation modeling (SEM) were used to test the structural validity of HNCPDS. Cronbach's alpha coefficient, Spearman-Brown coefficient and Intra-class correlation coefficient (ICC) were used to test the internal consistency and retest reliability of HNCPDS. Multiple stepped-linear regression was used to analyze the risk factors of psychological disorder, and Pearson correlation coefficient was used to analyze the correlation between psychosocial distress and quality of life (QOL). The HNCPDS consisted of 14 items, which were divided into 3 subscales: 3 items for cancer discrimination, 5 items for anxiety and depression, and 6 items for social phobia. The HNCPDS had good validity [KMO coefficient was 0.947, Bartlett's test was 5027.496 (P < 0.001), Cumulative variance contribution rate was 75.416%, and all factor loadings were greater than 0.55], reliability (Cronbach's alpha coefficient was 0.954, Spearman-Brown coefficient was 0.955, test-retest reliability was 0.845) and acceptability [average completion time (14.31 ± 2.354 min) and effective completion rate of 90.63%]. Financial burden, sex, age and personality were found to be independent risk factors for HNCPDS (P < 0.05), and patients with higher HNCPDS scores reported a lower QOL (P < 0.01). The HNCPDS is effective and reliable in early identification and assessment of the level of psychosocial distress in patients with head and neck cancer, which can provide an effective basis for health education, psychological counseling, and social support in the future.

Activation of trace amine-associated receptor 1 ameliorates PTSD-like symptoms.

Trace amine-associated receptor 1 (TAAR1) negatively modulates monoaminergic transmission in the mammalian brain and participates in many psychiatric disorders. Preclinical evidence indicate that selective TAAR1 agonists have anxiolytic effects and anti-stress properties. Post-traumatic stress disorder (PTSD) is an anxiety disorder triggered by experiencing or witnessing traumatic stressors. However, it remains unknown whether TAAR1 is involved in PTSD. Here, we investigated the role of TAAR1 in two PTSD animal models, including single prolonged stress (SPS)-induced impairment of fear extinction and stress-enhanced fear learning (SEFL). SPS decreased TAAR1 mRNA levels in the prefrontal cortex and ventral tegmental area. Acute treatment of the TAAR1 partial agonist RO5263397 attenuated SPS-induced anxiety-like behavior evaluated by the elevated-plus maze test. Compared to non-stressed animals, rats that experienced SPS showed higher freezing levels in the extinction retention test, indicating an impairment of fear extinction retention after SPS exposure. Acute and chronic treatment of RO5263397 ameliorated SPS-induced impairment of fear extinction retention. In the SEFL model, compared to the No-shock group, rats that experienced severe foot shock before fear conditioning showed higher freezing levels during the tests, indicating enhanced fear learning after stress exposure. Chronic treatment of RO5263397 partially attenuated the SEFL. Moreover, chronic treatment with the selective TAAR1 full agonist RO5166017 completely prevented the SEFL. Taken together, these data showed that pharmacological activation of TAAR1 could ameliorate PTSD-like symptoms. The present study thus provides the first evidence that TAAR1 might participate in the development of PTSD, and TAAR1 agonists could be potential pharmacological treatments for this disorder.

Antinociceptive effects of α2/α3-subtype selective GABAA receptor positive allosteric modulators KRM-II-81 and NS16085 in rats: behavioral specificity.

Recent studies suggest that amongst the GABAA receptor subtype heterogeneity, α2/α3 subunits of GABAA receptors mediate pain processing. Therefore, α2/α3-subtype selective GABAA receptor positive allosteric modulators (PAMs) may be candidate analgesics. Antinociceptive effects of α2/α3-subtype selective GABAA receptor PAMs have been reported, but the behavioral effects of these compounds have not been systematically evaluated. This study examined the behavioral effects of two α2/α3 subtype-selective GABAA receptor PAMs, KRM-II-81 and NS16085, in male rats. The antinociceptive effects of KRM-II-81 and NS16085 were examined using rat models of inflammatory (complete Freund's adjuvant) and neuropathic pain (chronic constriction injury). The effect of KRM-II-81 on affective pain was measured using the place escape/avoidance paradigm (PEAP). Rate-response of food-maintained operant responding, horizontal wire test, and the spontaneous alternation T-maze, were assessed to study the side-effect profiles of KRM-II-81 and NS16085. The benzodiazepine midazolam was used as a comparator in these studies. KRM-II-81 and NS16085 attenuated mechanical allodynia but not thermal hyperalgesia in both pain states, and their effects were attenuated by the benzodiazepine receptor antagonist flumazenil. KRM-II-81 attenuated affective pain-related behavior in the PEAP test. In the operant responding procedure and horizontal wire test, only midazolam produced significant effects at the dose that produced maximal antinociception. In the T-maze assay, only midazolam significantly decreased the percentage of alternation at an antinociceptive dose. Thus, KRM-II-81 and NS16085 but not midazolam selectively produced antinociceptive effects. Collectively, these data suggest that α2/α3-subtype selective GABAA PAMs could be a novel class of analgesics and warrant further investigation. Significance Statement This study demonstrates that α2/α3-subtype selective GABAA PAMs KRM-II-81 and NS16085 produce selective antinociceptive effects devoid of sedation, myorelaxation, cognitive impairment in two rat models of persistent pain. Unlikely classical benzodiazepines, this study supports the development of α2/α3-subtype selective GABAA PAMs as safe and novel analgesics for pain management.

Routes to high-performance layered oxide cathodes for sodium-ion batteries.

Sodium-ion batteries (SIBs) are experiencing a large-scale renaissance to supplement or replace expensive lithium-ion batteries (LIBs) and low energy density lead-acid batteries in electrical energy storage systems and other applications. In this case, layered oxide materials have become one of the most popular cathode candidates for SIBs because of their low cost and comparatively facile synthesis method. However, the intrinsic shortcomings of layered oxide cathodes, which severely limit their commercialization process, urgently need to be addressed. In this review, inherent challenges associated with layered oxide cathodes for SIBs, such as their irreversible multiphase transition, poor air stability, and low energy density, are systematically summarized and discussed, together with strategies to overcome these dilemmas through bulk phase modulation, surface/interface modification, functional structure manipulation, and cationic and anionic redox optimization. Emphasis is placed on investigating variations in the chemical composition and structural configuration of layered oxide cathodes and how they affect the electrochemical behavior of the cathodes to illustrate how these issues can be addressed. The summary of failure mechanisms and corresponding modification strategies of layered oxide cathodes presented herein provides a valuable reference for scientific and practical issues related to the development of SIBs.

Nickel Nanoparticles Protruding from Molybdenum Carbide Micropillars with Carbon Layer-Protected Biphasic 0D/1D Heterostructures for Efficient Water Splitting.

It remains a tremendous challenge to achieve high-efficiency bifunctional electrocatalysts for both the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER) for hydrogen production by water splitting. Herein, a novel hybrid of 0D nickel nanoparticles dispersed on the one-dimensional (1D) molybdenum carbide micropillars embedded in the carbon layers (Ni/Mo2C@C) was successfully prepared on nickel foam by a facile pyrolysis strategy. During the synthesis process, the nickel nanoparticles and molybdenum carbide were simultaneously generated under H2 and C2H2 mixed atmospheres and conformally encapsulated in the carbon layers. Benefiting from the distinctive 0D/1D heterostructure and the synergistic effect of the biphasic Mo2C and Ni together with the protective effect of the carbon layer, the reduced activation energy barriers and fast catalytic reaction kinetics can be achieved, resulting in a small overpotential of 96 mV for the HER and 266 mV for the OER at the current density of 10 mA cm-2 together with excellent durability in 1.0 M KOH electrolyte. In addition, using the developed Ni/Mo2C@C as both the cathode and anode, the constructed electrolyzer exhibits a small voltage of 1.55 V for the overall water splitting. The novel designed Ni/Mo2C@C may give inspiration for the development of efficient bifunctional catalysts with low-cost transition metal elements for water splitting.

Sodium Carbonate-Promoted Formation of 5-Amino-1,2,4-thiadiazoles and 5-Amino-1,2,4-selenadiazoles with Elemental Sulfur and Selenium.

Sodium carbonate-promoted facile synthesis of 5-amino-1,2,4-thiadiazoles and 5-amino-1,2,4-selenadiazoles with elemental sulfur and selenium, respectively, was developed. This method was carried out with O2 in the air as the green oxidant, and it has several advantages, including low cost, low toxicity, and stable sulfur and selenium sources, good to excellent yields with water as the sole byproduct, simple operation, and a broad substrate scope. Preliminary mechanistic studies indicate that the formation of the 1,2,4-thiadiazole ring and the 1,2,4-selenadiazole ring undergoes different processes.

Analysis of fertility intention to have a third child among childbearing age women in Wanzhou District of Chongqing Municipality and its influencing factors / 重庆医学

Objective To survey the current situation of fertility intention to have a third child among childbearing age women in Wanzhou District of Chongqing Municipality under the background of the new fer-tility policy,and to analyze its influencing factors.Methods The convenience sampling method was adopted to conduct the survey on the third child fertility intention by the self-designed questionnaire and the Question-naire Star platform among the childbearing women with one child or two children in Wanzhou District of Chongqing Municipality from September to October 2022.The multiple linear regression analysis and two-step cluster analysis were used to explore the influencing factors.Results A total of 632 questionnaires were re-ceived,32 invalid questionnaires were excluded,and the effective recovery rate was 94.9％.The score of fertili-ty intention to have a third child in the respondents was(12.81±2.83)points.The multiple linear regression analysis showed that the age,marital status,place of residence,spouse cultural degree,family rearing child model,whether the family can provide support and previous vaginal delivery history were the influencing fac-tors of fertility intention to have a third child among the childbearing age women in this place(P＜0.05).The two step cluster analysis showed that"obstetrician/midwife's help"was the most important predictive factor for the childbearing age women to choose to have a third child.Conclusion The current situation of childbear-ing age women's fertility intention to have a third child in Wanzhou District of Chongqing Municipality is not optimistic.It is necessary to create the positive factors that encourage childbearing age women to make deci-sion about having a third child.

Construction and validation of a model for predicting the risk of in-hospital cardiac arrest in emergency rooms / 中华急诊医学杂志

Objective:The predictive model of cardiac arrest in the emergency room was constructed and validated based on Logistic regression.Methods:This study was a retrospective cohort study. Patients admitted to the emergency room of the First Affiliated Hospital of Xinjiang Medical University from January 2020 to July 2021 were included. The general information, vital signs, clinical symptoms, and laboratory examination results of the patients were collected, and the outcome was cardiac arrest within 24 hours. The patients were randomly divided into modeling and validation group at a ratio of 7:3. LASSO regression and multivariable logistic regression were used to select predictive factors and construct a prediction model for cardiac arrest in the emergency room. The value of the prediction model was evaluated using the area under the receiver operator characteristic curve (AUC), calibration curve, and decision curve analysis (DCA).Results:A total of 784 emergency room patients were included in the study, 384 patients occurred cardiac arrest. The 10 variables were ultimately selected to construct a risk prediction model for cardiac arrest: Logit( P)= -4.503+2.159×modified early warning score (MEWS score)+2.095×chest pain+1.670×abdominal pain+ 2.021×hematemesis+2.015×cold extremities+5.521×endotracheal intubation+0.388×venous blood lactate-0.100×albumin+0.768×K ++0.001×D-dimer. The AUC of the model group was 0.984 (95% CI: 0.976-0.993) and that of the validation group was 0.972 (95% CI: 0.951-0.993). This prediction model demonstrates good calibration, discrimination, and clinical applicability. Conclusions:Based on the MEWS score, chest pain, abdominal pain, hematemesis, cold extremities, tracheal intubation, venous blood lactate, albumin, K +, and D-dimer, a predictive model for cardiac arrest in the in-hospital emergency room was constructed to predict the probability of cardiac arrest in emergency room patients and adjust the treatment strategy in time.

Application and reflection on smart Party building management platform under the new situations / 现代医院

To date,the information technology develops rapidly and the dawn of digital era comes just around the cor-ner.Under these new situations,smart Party building management platforms stand as a new impetus,energizing the Party build-ing efforts with robust capabilities for data storage,analysis,automatic computation,and administration.These platforms provide comprehensive data support that enhances the precision and efficiency of Party building.This leads to an invigorated process of continuous innovation and high-quality development within the Party building.This article delves into the practical application of the current unit's smart party building management platform,examining the challenges encountered during its operation.It also posits several reflections and strategic responses aimed at elevating the scientific management standards of party building.

Analysis of retinal and choroidal blood flow density in the macular areas of both eyes of children with mild monocular myopia / 中国医科大学学报

Objective To assess retinal and choroidal blood flow density in the macular regions of children diagnosed with unilateral low myopia using optical coherence tomography angiography(OCTA).This study aimed to investigate the clinical significance of these mea-surements.Methods A cross-sectional study was conducted on 90 eyes of 45 children with monocular myopia and adolescents aged 8 to 14 years who visited the outpatient department of the Ophthalmology of Dalian Third People's Hospital between June 2022 and February 2023.Optometry was performed after a 1%cyclopentolate cycloplegic muscle paralysis.Eyes with spherical equivalent(SE)-3.00 D to-0.50 D were included in the myopia group,whereas those with SE-0.25 D to＜+2.00 D were placed in the non-myopia group.The Master system was used to measure axial length(AL)and corneal curvature radius(CR),and to calculate AL/CR.Heidelberg spectral-domain optical coherence tomography(SD-OCT)was used to perform horizontal linear scanning of the macular area to obtain subfoveal choroidal thickness(SFCT).The OCTA module was used to obtain 3 mm×3 mm choroidal blood flow images,which were imported into ImageJ graphics processing software to obtain the blood flow densities of the superficial choroidal plexus(SCP),deep choroidal plexus(DCP),choroidal capillary(CC),and foveal avascular zone(FAZ).Pearson's correlation was used to examine the correlations between each blood flow parameter and age,AL,CR,AL/CR,and SFCT.Results The SE and SFCT of the myopia group were smaller(P＜0.05)than those of the non-myopia group,whereas the AL and AL/CR were significantly larger(P＜0.05)than those of the non-myopia group.The DCP blood flow density in the myopia group was significantly lower than that in the non-myopia group(P＜0.01).There was no statistically sig-nificant difference between the residual blood flow parameters of the myopia and non-myopia groups(P＞0.05).The Pearson's correlation analysis indicated that the SCP and DCP blood flow densities in the myopia group were positively correlated with SE(r= 0.611,0.731,P＜0.05),negatively correlated with AL(r=-0.568,-0.712,P＜0.05),and negatively correlated with AL/CR(r=-0.557,-0.564,P＜0.05).The SCP and DCP blood flow densities were negatively correlated with AL/CR in the non-myopia group(r=-0.615,-0.656,P＜0.05).The CC density and FAZ area in the two groups did not correlate with age,SE,AL,CR,AL/CR,or SFCT(P＞0.05).Conclusion Com-pared to non-myopic eyes,the eyes of children with mild monocular myopia had lower DCP blood flow density.Moreover,retinal blood flow density in myopic eyes was correlated with SE,AL,and AL/CR,whereas retinal blood flow density in non-myopic eyes was only correlated with AL/CR.

Effects of PATL1 on the proliferation and migration of gastric cancer cells and its mechanism of action / 安徽医科大学学报

Objective @#Objective @*Methods @#The expression levels of PATL1 in pancar- cinoma，gastric cancer and normal tissues were analyzed by TCGA database．The expression level of PATL1 in 40 human gastric cancer tissues and paired adjacent tissues was evaluated by quantitative real-time PCR (RT-qPCR) . The Kaplan-Meier Plotter database was used to analyze the prognosis of PATL1 in gastric cancer patients．The gas- tric cancer cell line AGS was transfected with PATL1 interference vector，and the interference effect was evaluated by RT-qPCR. The effects of PATL1 on the proliferation and migration of AGS were detected by cell counting kit-8 ( CCK-8) ，Transwell test and scratch healing test．The effects of interference with PATL1 on the expression of cel- lular-myelocytomatosis viral oncogene ( c-Myc) and autophagy related 7 ( ATG7) proteins in gastric cancer cells were detected by Western blot assay. @*Results @#RT-qPCR showed that the expression of PATL1 in human gastric cancer tissue was higher than that in normal gastric tissue (P＜0. 001) ，and PATL1 was correlated with the progno- sis of patients with enteric gastric cancer (P＜0. 000 1) ．After PATL1 was knocked down，the number of prolifera- ting and migrating gastric cancer cells decreased (P＜0. 05) ．Western blot test results showed that the expression level of ATG7 protein decreased after PATL1 was knocked down (P＜0. 05) ．@*Conclusion @#PATL1 may inhibit the proliferation and migration of gastric cancer cells through crosstalk with c-Myc and ATG7 .

Application Study of Enzyme Inhibitors and Their Conformational Optimization in The Treatment of Alzheimer’s Disease / 生物化学与生物物理进展

Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive dysfunction and behavioral impairment, and there is a lack of effective drugs to treat AD clinically. Existing medications for the treatment of AD, such as Tacrine, Donepezil, Rivastigmine, and Aducanumab, only serve to delay symptoms and but not cure disease. To add insult to injury, these medications are associated with very serious adverse effects. Therefore, it is urgent to explore effective therapeutic drugs for AD. Recently, studies have shown that a variety of enzyme inhibitors, such as cholinesterase inhibitors, monoamine oxidase (MAO)inhibitors, secretase inhibitors, can ameliorate cholinergic system dysfunction, Aβ production and deposition, Tau protein hyperphosphorylation, oxidative stress damage, and the decline of synaptic plasticity, thereby improving AD symptoms and cognitive function. Some plant extracts from natural sources, such as Umbelliferone, Aaptamine, Medha Plus, have the ability to inhibit cholinesterase activity and act to improve learning and cognition. Isochromanone derivatives incorporating the donepezil pharmacophore bind to the catalytic active site (CAS) and peripheral anionic site (PAS) sites of acetylcholinesterase (AChE), which can inhibit AChE activity and ameliorate cholinergic system disorders. A compound called Rosmarinic acid which is found in the Lamiaceae can inhibit monoamine oxidase, increase monoamine levels in the brain, and reduce Aβ deposition. Compounds obtained by hybridization of coumarin derivatives and hydroxypyridinones can inhibit MAO-B activity and attenuate oxidative stress damage. Quinoline derivatives which inhibit the activation of AChE and MAO-B can reduce Aβ burden and promote learning and memory of mice. The compound derived from the combination of propargyl and tacrine retains the inhibitory capacity of tacrine towards cholinesterase, and also inhibits the activity of MAO by binding to the FAD cofactor of monoamine oxidase. A series of hybrids, obtained by an amide linker of chromone in combine with the benzylpiperidine moieties of donepezil, have a favorable safety profile of both cholinesterase and monoamine oxidase inhibitory activity. Single domain antibodies (such as AAV-VHH) targeted the inhibition of BACE1 can reduce Aβ production and deposition as well as the levels of inflammatory cells, which ultimately improve synaptic plasticity. 3-O-trans-p-coumaroyl maslinic acid from the extract of Ligustrum lucidum can specifically inhibit the activity of γ-secretase, thereby rescuing the long-term potentiation and enhancing synaptic plasticity in APP/PS1 mice. Inhibiting γ-secretase activity which leads to the decline of inflammatory factors (such as IFN-γ, IL-8) not only directly improves the pathology of AD, but also reduces Aβ production. Melatonin reduces the transcriptional expression of GSK-3β mRNA, thereby decreasing the levels of GSK-3β and reducing the phosphorylation induced by GSK-3β. Hydrogen sulfide can inhibitGSK-3β activity via sulfhydration of the Cys218 site of GSK-3β, resulting in the suppression of Tau protein hyperphosphorylation, which ameliorate the motor deficits and cognitive impairment in mice with AD. This article reviews enzyme inhibitors and conformational optimization of enzyme inhibitors targeting the regulation of cholinesterase, monoamine oxidase, secretase, and GSK-3β. We are hoping to provide a comprehensive overview of drug development in the enzyme inhibitors, which may be useful in treating AD.

The Functional Role of SUMOylation in The Tumor Microenvironment / 生物化学与生物物理进展

Tumors continue to be a major challenge in human survival that we have yet to overcome. Despite the variety of treatment options available, we have not yet found an effective method. As more and more research is conducted, attention has been turned to a new field for tumor treatment—the tumor microenvironment (TME). This is a dynamic and complex environment consisting of various matrix cells surrounding cancer cells, including surrounding immune cells, blood vessels, extracellular matrix, fibroblasts, bone marrow-derived inflammatory cells, signaling molecules, and some specific cell types. Firstly, endothelial cells play a key role in tumor development and the immune system’s protection of tumor cells. Secondly, immune cells, such as macrophages, Treg cells, Th17 cells, are widely involved in various immune responses and activities in the human body, such as inflammation responses promoting survival carefully orchestrated by the tumor. Even though many studies have extensively researched the TME and found many research schemes, so far, no key effective method has been found to treat tumors by affecting the TME. The TME is a key interaction area between the host immune system and the tumor. Cells within the TME influence each other and interact with cancer cells to affect cancer cell invasion, tumor growth, and metastasis. This is a new direction for cancer treatment. In the complex environment of the TME, post-translational modifications (PTMs) of proteins have been proven to play an important role in the TME. PTMs are dynamic, strictly regulated changes to proteins that control their function by regulating their structure, spatial location, and interaction. Among PTMs, a reversible post-translational modification called SUMOylation is a common regulatory mechanism in cellular processes. It is a post-translational modification that targets lysine residues with a small ubiquitin-like modifier (SUMO) in a reversible post-translational modification manner. SUMOylation is widely involved in carcinogenesis, DNA damage response, cancer cell proliferation, metastasis, and apoptosis, playing a pivotal role in the TME, such as DNA damage repair, tumor metastasis, and also participates in immune cell differentiation, activation, and inhibition of immune cells. On the other hand, SUMO or sentrin-specific protease (SENP) inhibitors can interfere with the SUMOylation process, thereby affecting many biological processes, including immune response, carcinogenesis, cell cycle progression, and cell apoptosis, etc. In summary, this review aims to introduce the dynamic modification of protein SUMOylation on various immune cells and the application of various inhibitors, thereby exploring its role in the TME. This is a challenging but hopeful field, and we look forward to future research that can bring more breakthroughs. In conclusion, the TME is a complex and dynamic environment that plays a crucial role in the development and progression of tumors. Understanding the intricate interactions within the TME and the role of PTMs, particularly SUMOylation, could provide valuable insights into the mechanisms of tumor development and potentially lead to the development of novel therapeutic strategies. The study of SUMOylation and its effects on various immune cells in the TME is an exciting and promising area of research that could significantly advance our understanding of tumor biology and potentially lead to the development of more effective treatments for cancer. This is a challenging but hopeful field, and we look forward to future research that can bring more breakthroughs.

Research on the value of double closed-loop management mode in maintenance and fault control of hemodialysis machine / 中国医学装备

Objective:To construct a double-closed-loop management model for medical equipment and explore its application value in hemodialysis machine maintenance and fault management.Methods:Based on the closed-loop management of clinical operation of medical equipment and the closed-loop management of technical support,a dual closed-loop management model of equipment was constructed.65 hemodialysis machines in clinical use in Huashan Hospital Fudan University from January 2021 to January 2023 were selected and divided into a conventional mode and double-closed-loop mode according to different management modes.The conventional mode adopted conventional equipment management methods,and the double-closed-loop mode adopted a double-closed-loop management model.The cost-effectiveness,social benefit,failure occurrence,effective management quality matters,disinfection status,average patient waiting time and satisfaction were compared between the two groups.Results:The hemodialysis machine operating profit growth rate,diagnosis and treatment cost growth rate,service life index,scientific research service growth rate,diagnosis and treatment service growth rate,startup rate and operation rate of the double-closed-loop mode were(3.95±1.04)%,(3.80±0.58)%,(1.58±0.31)%,(4.30±0.95)%,(7.91±1.58)%,(96.58±2.76)%and(89.90±5.58)%,which were higher than those of the Conventional mode,the difference was statistically significant(t=5.418,10.070,7.490,17.570,11.820,8.849,6.840,P<0.05).The technical support expenses growth rate,bacterial colony count,bacterial endotoxin content and average patient waiting time of patients in the Double-closed-loop mode were(2.60±0.33)%,(0.370±0.008)cfu/ml,(0.0063±0.0011)EU/ml and(0.76±0.13)h,which were less than those of the conventional mode,the difference was statistically significant(t=23.040,82.985,14.482,19.530,P<0.05).The incidence rate of hemodialysis machine failure in the double-closed-loop mode was 9.23%(6/65),which was lower than that in the conventional mode,the difference was statistically significant(x2=6.392,P<0.05);among the 120 items of management data collected,quality control testing,maintenance and repair,clinical operation,information data,and scrap processing effectiveness rates were 95.83%(115/120),89.17%(107/120),96.67%(116/120),95.00%(114/120),and 97.50%(117/120),respectively,which were higher than those of the conventional mode,the difference was statistically significant(x2=15.238,16.596,9.808,15.585,16.119,P<0.05).Conclusion:The application of closed-loop management model to hemodialysis machine maintenance and fault management can effectively improve equipment cost-effectiveness,social benefits,management quality and patient satisfaction,and reduce the incidence of faults.

Binding and carrying role of human serum albumin from various sources to sphingosine-1-phosphate / 中国输血杂志

【Objective】 To investigate the binding and carrying effects of human serum albumin (HSA) from various sources on sphingosine-1-phosphate (S1P). 【Methods】 Utilizing human plasma-derived HSA (pHSA) and recombinant HSA (rHSA) samples as the focal points of our investigation, LC-MS/MS technology was employed to meticulously compare and analyze the disparities in S1P content among the aforementioned samples. Subsequently, under physiological concentration conditions, S1P was directly introduced to HSA samples for loading processing, facilitating a comprehensive comparison of the binding efficacy of HSA from different sources to S1P. Within a serum-free culture setting, HSA samples from various sources were co-cultured with HUVEC cells. The alterations in S1P content within the cell culture supernatant across different treatment groups were meticulously analyzed, allowing for a nuanced comparison of the S1P carry effects exerted by HSA from different sources on cells.The interaction between HSA and S1P molecules from different sources was analyzed and their affinity was calculated using surface plasmon resonance (SPR) technology. Furthermore, leveraging AutoDock Vina software and the Molprophet platform, the molecular docking analysis of HSA and S1P was conducted, aiming to predict the key binding pocket domain of S1P within HSA. 【Results】 All pHSA samples exhibited detectable levels of S1P (ranging from 3.31±0.03 to 30.35±0.07 μg/L), with significant variations observed among pHSA samples from different manufacturers (P<0.001). Conversely, S1P was undetectable in all rHSA samples. Upon load treatment, the binding affinity of HSA from diverse sources to S1P demonstrated significant discrepancies (P<0.001), with rHSA exhibiting approximately double the average S1P loading compared to pHSA (ΔCrHSA=801.75±142.45 μg/L vs ΔCpHSA=461.94±85.73 μg/L; P<0.001, t=5.006). Co-culture treatment outcomes revealed a significant elevation in S1P concentration within the supernatant after 6 hours of co-culture across all HSA sample processing groups with HUVEC cells, while no changes were observed in the supernatant of the blank control group. Notably, significant differences in supernatant S1P concentration were observed among treatment groups at 6 h, 12 h, and 24 h (P<0.001). SPR analysis unveiled a stronger affinity of pHSA for S1P compared to rHSA (KDpHSA-S1P: 2.38E-06, KDrHSA-S1P: 3.72E-06). Molecular docking analysis and binding pocket prediction suggested that the key binding pocket of HSA and S1P may reside in the IB subdomain of the HSA molecule. 【Conclusion】 HSA from various sources exhibits distinct binding and carrying effects on S1P, which appear to be closely associated with the IB subdomain of the HSA molecule.

Association between the ratio of dietary vitamin A to body weight and hypertension in children / 中国学校卫生

Objective@#To explore the relationship between the ratio of dietary vitamin A (VitA) to body weight and hypertension among children, so as to provide a reference for blood pressure control through dietary nutritional interventions and childhood hypertension prevention.@*Methods@#Utilizing the baseline survey and followup sample data from the Healthy Children Cohort established in urban and rural areas of Chongqing from 2014 to 2019, structured quantitative dietary questionnaire and selfdesigned questionnaire were used to investigate the information of dietary intake and socioeconomic characteristics of 15 279 children, as well as blood pressure, height, weight measurement. The ratio of dietary VitA to body weight was divided into four groups based on quartiles [≤P25(Q1), >P25~P50(Q2), >P50~P75(Q3), >P75(Q4)]. Generalized linear regression models and Logistic regression models were used to analyze the correlation between ratio of dietary VitA to body weight with blood pressure levels and prevalence of hypertension.@*Results@#The results of the 2014 baseline survey indicated that, after adjusting for confounding factors such as demographic indicators and nutritional intake, significant differences were observed in systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) among different groups categorized by the ratio of dietary VitA to body weight (F=157.57, 44.71, 95.92, P<0.01). The baseline ratio of dietary VitA to body weight in children exhibited a negative correlation with DBP, SBP and MAP at baseline and in 2019[baseline: β(95%CI)=-0.65(-0.89--0.42), -0.22(-0.42--0.01), -0.36(-0.56--0.16); 2019: β(95%CI)=-0.77(-1.34--0.19), -0.62(-1.21--0.02), -0.77(-1.34--0.19), P＜0.05]. Compared to Q1 group, the risk of hypertension decreased among children in Q4 at baseline and followup in 2019 [OR(95%CI)=0.63(0.49-0.81), 0.18(0.08-0.42), P<0.01].@*Conclusions@#The ratio of dietary VitA to body weight is significantly negatively correlated with blood pressure levels among children, and dietary VitA deficiency is an independent risk factor for hypertension among children. Measures should be taken to actively adjust childrens dietary nutrition and reduce the risk of childhood hypertension.

Genetic and phenotypic analysis of MYO15A rare variants associated with autosomal recessive hearing loss / 临床耳鼻咽喉头颈外科杂志

Objective:To analyze the phenotype and genotype characteristics of autosomal recessive hearing loss caused by MYO15A gene variants, and to provide genetic diagnosis and genetic counseling for patients and their families. Methods:Identification of MYO15A gene variants by next generation sequencing in two sporadic cases of hearing loss at Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine. The sequence variants were verified by Sanger sequencing.The pathogenicity of these variants was determined according to the American College of Medical Genetics and Genomics（ACMG） variant classification guidelines, in conjuction with clinical data. Results:The probands of the two families have bilateral,severe or complete hearing loss.Four variants of MYO15A were identified, including one pathogenic variant that has been reported, two likely pathogenic variants,and one splicing variant of uncertain significance. Patient I carries c. 3524dupA（p. Ser1176Valfs*14）, a reported pathogenic variant, and a splicing variant c. 10082+3G>A of uncertain significance according to the ACMG guidelines. Patient I was treated with bilateral hearing aids with satisfactory effect, demonstrated average hearing thresholds of 37.5 dB in the right ear and 33.75 dB in the left ear. Patient Ⅱ carries c. 7441_7442del（p. Leu2481Glufs*86） and c. 10250_10252del（p. Ser3417del）,a pair of as likely pathogenic variants according to the ACMG guidelines. Patient Ⅱ, who underwent right cochlear implantation eight years ago, achieved scores of 9 on the Categorical Auditory Performance-Ⅱ（CAP-Ⅱ） and 5 on the Speech Intelligibility Rating（SIR）. Conclusion:This study's discovery of the rare c. 7441_7442del variant and the splicing variant c. 10082+3G>A in the MYO15A gene is closely associated with autosomal recessive hearing loss, expanding the MYO15A variant spectrum. Additionally, the pathogenicity assessment of the splicing variant facilitates classification of splicing variations.

The imidazoline I2 receptor agonist 2-BFI reduces abuse-related effects of morphine: self-administration and drug discrimination.

RATIONALE: Increasing evidence shows that imidazoline I2 receptor agonists enhance opioid-induced analgesia, suggesting that the combination of I2 receptor agonists with opioids could be a favorable strategy for pain control. However, the effect of I2 receptor agonists on the abuse liability of opioids is unknown. This study examined the impact of the I2 receptor agonist 2-BFI on some abuse-related behavioral effects of the opioid morphine in rats. OBJECTIVES: The von Frey filament test was used to determine the antinociceptive effects of 2-BFI (intravenous, i.v.) in a rat model of complete Freund's adjuvant (CFA)-induced inflammatory pain. IV self-administration was used to assess the reinforcing effects of 2-BFI alone and to assess the effects of non-contingent injections of 2-BFI (i.p.) on morphine self-administration. A two-lever drug discrimination paradigm in which rats were trained to discriminate 3.2 mg/kg morphine (i.p.) from saline was used to examine whether 2-BFI or another I2 receptor agonist 2-(4,5-dihydroimidazol-2-yl)quinoline hydrochloride (BU224) affected the discriminative stimulus effects of morphine. RESULTS: 2-BFI could not maintain reliable self-administration behavior in rats with no pain or CFA-treated inflammatory pain. However, pretreatment with 2-BFI (i.p.) produced dose-dependent decreases in the dose-effect curve of morphine self-administration. Both 2-BFI and BU224 did not substitute for morphine but significantly attenuated the discriminative stimulus effects of morphine. CONCLUSIONS: These results suggest that I2 receptor agonists do not enhance, but in fact appear to decrease, the abuse liability of opioids, further supporting the potential utility of I2 receptor agonist-opioid combination therapy for pain control.

TAAR1 as an emerging target for the treatment of psychiatric disorders.

Trace amines, a group of amines expressed at the nanomolar level in the mammalian brain, can modulate monoamine transmission. The discovery of and the functional research on the trace amine-associated receptors (TAARs), especially the most well-characterized TAAR1, have largely facilitated our understanding of the function of the trace amine system in the brain. TAAR1 is expressed in the mammalian brain at a low level and widely distributed in the monoaminergic system, including the ventral tegmental area and substantial nigra, where the dopamine neurons reside in the mammalian brain. Growing in vitro and in vivo evidence has demonstrated that TAAR1 could negatively modulate monoamine transmission and play a crucial role in many psychiatric disorders, including schizophrenia, substance use disorders, sleep disorders, depression, and anxiety. Notably, in the last two decades, many studies have repeatedly confirmed the pharmacological effects of the selective TAAR1 ligands in various preclinical models of psychiatric disorders. Recent clinical trials of the dual TAAR1 and serotonin receptor agonist ulotaront also revealed a potential efficacy for treating schizophrenia. Here, we review the current understanding of the TAAR1 system and the recent advances in the elucidation of behavioral and physiological properties of TAAR1 agonists evaluated both in preclinical animal models and clinical trials. We also discuss the potential TAAR1-dependent signaling pathways and the cellular mechanisms underlying the inhibitory effects of TAAR1 activation on drug addiction. We conclude that TAAR1 is an emerging target for the treatment of psychiatric disorders.

Association between serum PCSK9 and coronary heart disease in patients with type 2 diabetes mellitus.

BACKGROUND AND AIMS: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is considered a new biomarker for atherosclerosis, but its ability to predict cardiovascular outcomes has been controversial. This study aimed to address the lack of data on PCSK9, coronary heart disease (CHD) severity, and major cardiovascular events (MACEs) in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 2984 T2DM patients underwent selective coronary angiography, and their serum PCSK9 levels were measured using enzyme-linked immunosorbent assay. Correlation and logistic regression analyses were performed to investigate the association between PCSK9 expression and CHD severity. This study used Cox regression analysis to assess the association between circulating PCSK9 levels and the risk of MACEs. RESULTS: Circulating PCSK9 levels were significantly higher in the CHD group than in the non-CHD group [554.62 (265.11) ng/mL vs. 496.86 (129.05) ng/mL, p < 0.001]. Circulating PCSK9 levels positively correlated with CHD severity (diseased vessels: r = 0.35, p < 0.001; Gensini score: r = 0.46, p < 0.001). Elevated PCSK9 levels are an independent risk factor for CHD risk and severity (CHD group vs. non-CHD group: OR = 2.829, 95% CI: 1.771-4.520, p < 0.001; three vessel disease group vs. one vessel disease group: OR = 4.800, 95% CI: 2.387-9.652, p < 0.001; high GS group vs. low GS group: OR = 5.534, 95% CI: 2.733-11.208, p < 0.001). Through a six-year follow-up and multivariate Cox regression analysis, elevated circulating PCSK9 levels were found to be independently associated with MACEs in all participants (HR: 3.416, 5% CI: 2.485-4.697, p < 0.001; adjusted HR: 2.780, 95% CI: 1.930-4.004, p < 0.001). CONCLUSIONS: Serum PCSK9 levels were positively correlated with multi-vessel CHD and Gensini score. Elevated circulating PCSK9 levels are an independent risk factor for CHD and increased incidence of MACEs in T2DM.