Research on outpatient capacity planning combining lean thinking and integer linear programming.

BACKGROUND: The size and cost of outpatient capacity directly affect the operational efficiency of a whole hospital. Many scholars have faced the study of outpatient capacity planning from an operations management perspective. OBJECTIVE: The outpatient service is refined, and the quantity allocation problem of each type of outpatient service is modeled as an integer linear programming problem. Thus, doctors' work efficiency can be improved, patients' waiting time can be effectively reduced, and patients can be provided with more satisfactory medical services. METHODS: Outpatient service is divided into examination and diagnosis service according to lean thinking. CPLEX is used to solve the integer linear programming problem of outpatient service allocation, and the maximum working time is minimized by constraint solution. RESULTS: A variety of values are taken for the relevant parameters of the outpatient service, using CPLEX to obtain the minimum and maximum working time corresponding to each situation. Compared with no refinement stratification, the work efficiency of senior doctors has increased by an average of 25%. In comparison, the patient flow of associate senior doctors has increased by an average of 50%. CONCLUSION: In this paper, the method of outpatient capacity planning improves the work efficiency of senior doctors and provides outpatient services for more patients in need; At the same time, it indirectly reduces the waiting time of patients receiving outpatient services from senior doctors. And the patient flow of the associate senior doctors is improved, which helps to improve doctors' technical level and solve the problem of shortage of medical resources.

Mechanism of Chinese medicine for promoting blood circulation and removing blood stasis combined with platelet-rich plasma to improve steroid-induced necrosis of the femoral head / 中国组织工程研究

BACKGROUND:At present,it is found that both Chinese medicine for activating blood circulation and removing blood stasis and platelet-rich plasma technology can repair damaged blood vessels,promote vascular regeneration,rebuild blood supply in the femoral head,restore normal blood supply,and further promote osteogenesis.Both of them have certain advantages in early intervention of steroid-induced necrosis of femoral head.It can also further understand the mechanism of blood activating and stasis removing herbs and platelet-rich plasma technology in improving steroid-induced necrosis of the femoral head,and provide new ideas for future treatment. OBJECTIVE:To review the research progress of the mechanism of the combination of blood activating and blood stasis removing herbs and platelet-rich plasma technology on steroid-induced necrosis of the femoral head according to the related literature at home and abroad. METHODS:PubMed,Web of Science,Metstr,CNKI and WanFang databases were searched for relevant articles."Traditional Chinese medicine,signal pathways,steroid induced necrosis of femoral head,vascular endothelial growth factor,platelet rich plasma"were used as the Chinese and English search terms separately.The time limit for searching the literature was from January 2000 to July 2022,and 75 related articles were finally included. RESULTS AND CONCLUSION:Both Chinese medicine for activating blood circulation and removing blood stasis and platelet-rich plasma technology have certain advantages in intervening the early stage of steroid-induced necrosis of femoral head.For traditional Chinese medicine,both single and compound drugs can effectively alleviate the further development of steroid-induced necrosis of the femoral head.The specific mechanism is as follows:(1)The traditional Chinese medicine for activating blood circulation and removing blood stasis has a significant anticoagulation effect,which can antagonize the abnormal(hypercoagulable)state of blood caused by hormone drugs,and further restore the normal blood supply in the femoral head.(2)Traditional Chinese medicine for activating blood circulation and removing blood stasis can repair damaged vascular endothelium,regenerate blood vessels and remodel blood supply in the femoral head by activating vascular endothelial growth factor.(3)The traditional Chinese medicine of promoting blood circulation and removing blood stasis has the obvious effect of removing blood stasis,which can reduce the accumulation of fat cells in the bone marrow cavity and relieve the pressure in the femoral head.(4)Traditional Chinese medicine for promoting blood circulation and removing blood stasis can regulate relevant signal pathways,maintain bone metabolism,promote the differentiation and balance of osteoblasts and osteoclasts,and effectively reduce steroid-induced necrosis of the femoral head.In addition,platelet-rich plasma contains a large amount of high concentration of cell growth factor,which plays a positive role in osteogenesis and vascular regeneration,and can also improve the abnormal state of the blood.Traditional Chinese medicine for activating blood circulation and removing blood stasis combined with platelet-rich plasma technology can play their biological roles,and the intervention effect is more significant.

Targeting cAMP in D1-MSNs in the nucleus accumbens, a new rapid antidepressant strategy

Studies have suggested that the nucleus accumbens (NAc) is implicated in the pathophysiology of major depression; however, the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated. Here, we identified a specific reduction of cyclic adenosine monophosphate (cAMP) in the subset of dopamine D1 receptor medium spiny neurons (D1-MSNs) in the NAc that promoted stress susceptibility, while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors. Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons (D2-MSNs) of depressed mice, however, the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs. We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration, but not a lower dose. The fast onset property of crocin was verified through multicenter studies. Moreover, crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN. These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc, and provide a potential rapid antidepressant drug candidate, crocin.

Advances in the role of epigenetics in tuberculosis / 中华微生物学和免疫学杂志

Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis ( Mtb) that seriously endangers human health. Mtb induces epigenetic changes in the host to regulate host genome transcription and immune response, which plays an important role in the growth and replication of Mtb and the development and outcome of TB. Since epigenetic regulation occurs early and is reversible, it has been extensively studied in the pathogenesis of various diseases and has great potential as a molecular target. This paper reviewed the epigenetic changes in host after Mtb infection, including DNA methylation and miRNA, and summarized the role of epigenetics in the pathogenesis of TB and the research progress in potential diagnostic markers.

Effects of regulation of the PI3K/AKT signaling pathway by TYROBP on neuroinflammation and autophagy / 中华老年医学杂志

Objective:To investigate the effects of TYRO protein tyrosine-binding protein(TYROBP)on neuroinflammation and autophagy via the PI3K/AKT signaling pathway in a transgenic APP/ PS1 mouse model of AD. Methods:C57BL/6J, TYROBP-/- and APP/ PS1 transgenic male mice aged 15-month-old were randomly divided into 3 group: the C57BL/6J group, the TYROBP-/- group and the APP/ PS1 group, with 19 in each group.The eight-arm maze test and novel object recognition test were conducted to assess the learning and memory ability of mice.The activation of microglia and NLRP3 inflammasomes were assessed by immunofluorescence.The mRNA levels of TNF-α, IL-6 and IL-1β were measured by real-time PCR, and the protein expression levels of NLRP3, cleaved caspase-1, SQSTM1, LC3B, TYROBP, p-PI3K, PI3K, p-AKT and AKT were assayed by Western blot. Results:Compared with the C57BL/6J group, the learning and memory abilities were significantly decreased(all P<0.05), activated microglia and NLRP3 inflammasomes were increased(all P<0.05), the mRNA and protein expression levels of TNF-α, IL-6, and IL-1β were increased(all P<0.05)and the protein expression levels of LC3B-Ⅱ, SQSTM1, TYROBP, p-PI3K, p-AKT were increased(all P<0.05)in the APP/ PS1 group.Compared with C57BL/6J group, the protein expression levels of TNF-α, IL-6, IL-1β, LC3B Ⅱ, SQSTM1, p-PI3K and p-AKT were decreased(all P<0.05). Conclusions:TYROBP promotes the inflammatory response and inhibits autophagy possibly by activating the PI3K/AKT signaling pathway, thus participating in the occurrence and development of AD.

Inflammatory Mechanism of Coronary Heart Disease and Intervention Strategies of Chinese Medicine Based on ''Phlegm，Stasis，Toxin'' Theory / 中国实验方剂学杂志

More and more evidence shows that there is a close relationship between the inflammatory state and coronary heart disease. Inflammatory state triggers the damage of vascular endothelium in the early stage of coronary heart disease and ultimately mediates the formation of atherosclerotic plaque. The mechanism of occurrence and development of heart disease is of great significance. Phlegm is a pathological product formed by the subtle imbalance of the spleen and stomach in the transportation and transformation of water and grain. It is the general summary of a series of abnormally accumulated inflammatory substances， such as low density lipoprotein， inflammatory cells， and inflammatory factors. The nature of Phlegm determines the invasiveness and turbidity of Phlegm. Phlegm invades the meridians， causing damage to the meridians and gradually accumulating， which eventually causes the local meridian damage to aggravate. This process is similar to the persistent damage of the vascular endothelium caused by inflammation. Phlegm blocks the meridians， affects the operation of Qi and blood， causes Qi stagnation and blood stasis， and finally forms the outcome of heart and blood stasis. This process is similar to the mechanism of atherosclerotic plaques formed by continuous inflammatory damage. Heart blood stasis， depression and heat， heat toxin endogenous， forming the syndrome of heat toxin stasis， which is similar to the process of atherosclerotic plaque rupture and thrombosis causing acute cardiovascular events.The formation of Phlegm is rooted in the deficiency of spleen. Based on the ''phlegm，stasis，toxin'' theory， spleen deficiency is the intrinsic pathogenesis of the inflammatory state of coronary heart disease， and the invasion of phlegm， blood stasis of heart， heat and blood stasis are the evolution of inflammatory damage of coronary heart disease. Traditional Chinese medicine differentiation and treatment is based on strengthening the spleen and nourishing Qi to treat the root and removing phlegm and blood stasis， and clearing heat and detoxifying to treat symptoms. The related Chinese medicine compounds， Chinese patent medicines， and single Chinese medicines can reduce the inflammatory indicators of coronary heart disease， thereby improving the prognosis of coronary heart disease.

Imbalance of lymphoid cells in peripheral blood maintains the immunosuppression and promotes the development of lung adenocarcinoma / 细胞与分子免疫学杂志

Objectives Objectives To investigate how the imbalance of innate lymphoid cells (ILCs)in the peripheral blood of patients with lung adenocarcinoma affects the balance of downstream mononuclear macrophages and T helper (Th) cells, and to identify the impact of the imbalance of ILCs on the immune status and prognosis of lung adenocarcinoma. Methods The peripheral blood of 20 patients with lung adenocarcinoma and normal controls were collected. The percentage of ILCs, mononuclear macrophages and T lymphocyte in peripheral blood were analyzed by flow cytometry. The characteristic cytokine secretion levels of various types of immune cells in peripheral blood were detected by real-time fluorescence quantitative PCR. Results Compared with the normal controls, the proportion of M2 mononuclear macrophages, ILC1 and ILC2 in patients with lung adenocarcinoma was up-regulated, while the proportion of M1 mononuclear macrophages, CD4+ T and CD8+ T was down-regulated. The mRNA expression of related cytokines of M1 mononuclear macrophages and ILC1 were decreased; while the mRNA expression of related cytokines of M2 mononuclear macrophages and ILC2 were increased. Along with the decreased CD4+T cells-associated cytokine T-bet mRNA expression, and the increased GATA3 mRNA expression. Moreover, the expression of PD-1 in CD8+ T cells was also up-regulated. Conclusion The imbalance of ILCs in peripheral blood of patients with lung adenocarcinoma promotes the imbalance of mononuclear macrophages and Th cells, which altogether maintains the immunosuppression in patients with lung adenocarcinoma, and promotes the development of lung adenocarcinoma.

Fibroblast growth factor 21 (FGF21) attenuates tacrolimus-induced hepatic lipid accumulation through transcription factor EB (TFEB)-regulated lipophagy / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Tacrolimus (TAC), also called FK506, is one of the classical immunosuppressants to prevent allograft rejection after liver transplantation. However, it has been proved to be associated with post-transplant hyperlipemia. The mechanism behind this is unknown, and it is urgent to explore preventive strategies for hyperlipemia after transplantation. Therefore, we established a hyperlipemia mouse model to investigate the mechanism, by injecting TAC intraperitoneally for eight weeks. After TAC treatment, the mice developed hyperlipemia (manifested as elevated triglyceride (TG) and low-density lipoprotein cholesterol (LDL-c), as well as decreased high-density lipoprotein cholesterol (HDL-c)). Accumulation of lipid droplets was observed in the liver. In addition to lipid accumulation, TAC induced inhibition of the autophagy-lysosome pathway (microtubule-associated protein 1 light chain 3β (LC3B) II/I and LC3B II/actin ratios, transcription factor EB (TFEB), protein 62 (P62), and lysosomal-associated membrane protein 1 (LAMP1)) and downregulation of fibroblast growth factor 21 (FGF21) in vivo. Overexpression of FGF21 may reverse TAC-induced TG accumulation. In this mouse model, the recombinant FGF21 protein ameliorated hepatic lipid accumulation and hyperlipemia through repair of the autophagy-lysosome pathway. We conclude that TAC downregulates FGF21 and thus exacerbates lipid accumulation by impairing the autophagy-lysosome pathway. Recombinant FGF21 protein treatment could therefore reverse TAC-caused lipid accumulation and hypertriglyceridemia by enhancing autophagy.

Double-negative T cells: a promising avenue of adoptive cell therapy in transplant oncology / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Tumor recurrence is one of the major life-threatening complications after liver transplantation for liver cancer. In addition to the common mechanisms underlying tumor recurrence, another unavoidable problem is that the immunosuppressive therapeutic regimen after transplantation could promote tumor recurrence and metastasis. Transplant oncology is an emerging field that addresses oncological challenges in transplantation. In this context, a comprehensive therapeutic management approach is required to balance the anti-tumor treatment and immunosuppressive status of recipients. Double-negative T cells (DNTs) are a cluster of heterogeneous cells mainly consisting of two subsets stratified by T cell receptor (TCR) type. Among them, TCRαβ+ DNTs are considered to induce immune suppression in immune-mediated diseases, while TCRγδ+ DNTs are widely recognized as tumor killers. As a composite cell therapy, healthy donor-derived DNTs can be propagated to therapeutic numbers in vitro and applied for the treatment of several malignancies without impairing normal tissues or being rejected by the host. In this work, we summarized the biological characteristics and functions of DNTs in oncology, immunology, and transplantation. Based on the multiple roles of DNTs, we propose that a new balance could be achieved in liver transplant oncology using them as an off-the-shelf adoptive cell therapy (ACT).

Gut microbiota-based pharmacokinetic-pharmacodynamic study and molecular mechanism of specnuezhenide in the treatment of colorectal cancer targeting carboxylesterase / 药物分析学报

Specnuezhenide(SNZ)is among the main components of Fructus Ligustri Lucidi,which has anti-inflammation,anti-oxidation,and anti-tumor effect.The low bioavailability makes it difficult to explain the mechanism of pharmacological effect of SNZ.In this study,the role of the gut microbiota in the metabolism and pharmacokinetics characteristics of SNZ as well as the pharmacological meaning were explored.SNZ can be rapidly metabolized by the gut microbiome,and two intestinal bacterial metabolites of SNZ,salidroside and tyrosol,were discovered.In addition,carboxylesterase may be the main intestinal bacterial enzyme that mediates its metabolism.At the same time,no metabolism was found in the incubation system of SNZ with liver microsomes or liver homogenate,indicating that the gut microbiota is the main part involved in the metabolism of SNZ.In addition,pharmacokinetic studies showed that salidroside and tyrosol can be detected in plasma in the presence of gut microbiota.Interestingly,tumor development was inhibited in a colorectal tumor mice model administered orally with SNZ,which indicated that SNZ exhibited potential to inhibit tumor growth,and tissue distribution studies showed that salidroside and tyrosol could be distributed in tumor tissues.At the same time,SNZ modulated the structure of gut microbiota and fungal group,which may be the mechanism governing the antitumoral activity of SNZ.Furthermore,SNZ stimulates the secretion of short-chain fatty acids by intestinal flora in vitro and in vivo.In the future,targeting gut microbes and the interaction between natural products and gut microbes could lead to the discovery and development of new drugs.

Berberine ameliorates chronic kidney disease through inhibiting the production of gut-derived uremic toxins in the gut microbiota

At present, clinical interventions for chronic kidney disease are very limited, and most patients rely on dialysis to sustain their lives for a long time. However, studies on the gut-kidney axis have shown that the gut microbiota is a potentially effective target for correcting or controlling chronic kidney disease. This study showed that berberine, a natural drug with low oral availability, significantly ameliorated chronic kidney disease by altering the composition of the gut microbiota and inhibiting the production of gut-derived uremic toxins, including p-cresol. Furthermore, berberine reduced the content of p-cresol sulfate in plasma mainly by lowering the abundance of g_Clostridium_sensu_stricto_1 and inhibiting the tyrosine-p-cresol pathway of the intestinal flora. Meanwhile, berberine increased the butyric acid producing bacteria and the butyric acid content in feces, while decreased the renal toxic trimethylamine N-oxide. These findings suggest that berberine may be a therapeutic drug with significant potential to ameliorate chronic kidney disease through the gut-kidney axis.

Serum osteocalcin and diabetic peripheral neuropathy in male patients with diabetes / 中华内分泌代谢杂志

Objective:To investigate the association between serum bone turnover marker osteocalcin and the distal symmetric poly neuropathy(DSPN) in male diabetic patients.Methods:Clinical data from 370 male diabetic patients who admitted to Zhongshan Hospital, Fudan University from January 2020 to November 2021 were collected. These patients were grouped into tertiles by serum osteocalcin level: T1 group(osteocalcin<9.2 ng/mL, n=123), T2 group(osteocalcin 9.2-13 ng/mL, n=122), and T3 group(osteocalcin≥13 ng/mL, n=125). The percentage ratios of DSPN were compared among these groups. Using logistic regression model, the adjusted odds ratio ( OR) for DSPN was calculated. Results:There were 50(40.7%), 29(23.8%), 49(39.2%) patients with DSPN in T1, T2, and T3 group respectively. The ratio of patients with DSPN in osteocalcin T2 group were lower than that in the T1 and T3 groups. Further logistic regression showed a 133.9%( OR=2.339, 95% CI 1.097-4.988, P=0.028) and a 134.2%( OR= 2.342, 95% CI 1.040-5.275, P=0.039) increased risk for DSPN in the T1 and T3 group respectively compared with the T2 group, even after adjusted for age, diabetic duration, HbA 1C, diabetic complications, β cross-linked C-telopeptide of type Ⅰ collagen(CTXβ), 25-hydoxy vitamin D(25-OHD), bone mineral density, and treatment. Conclusions:The serum levels of bone turnover marker osteocalcin were associated with the occurrence of DSPN in male diabetic patients, a moderate level of bone turnover(the serum osteocalcin level of between 9.2 and 13 ng/mL for instance) might be protective for male diabetic patients from DSPN.

Tyrobp promotes neuroinflammation in Tourette's syndrome model mice and related mechanisms / 中华行为医学与脑科学杂志

Objective:To explore the effects and possible mechanisms of Tyrobp gene on neuroinflammation in Tourette's syndrome mice.Methods:Twenty C57BL/ 6J and Tyrobp knock-out male mice aged 6 weeks were randomly divided into 4 groups according to random number table method: WT+ NS group, Tyrobp -/-+ NS group, WT+ IDPN group and Tyrobp -/-+ IDPN group. Mice in WT+ IDPN group and Tyrobp -/-+ IDPN group were injected with IDPN intraperitoneally at a dose of 150 mg/kg·d, while mice in WT+ NS group and Tyrobp -/-+ NS group were injected with equal volume of normal saline, once a day for 7 days. Then stereotypical behavior of mice were evaluated. Western blot was used to detect the levels of Tyrobp, TNF-α, IL-6, IL-1β, TLR4, Myd88, p-NF-κB p65 and p-IκBα in the striatum of mice. Immunofluorescence staining was used to observe the activation of microglia. Statistical analysis was performed using GraphPad Prism 8.0 software, and t-test was used for comparison between two groups. One-way ANOVA was used to compare the means of multiple samples, and LSD test was used for further pairwise comparison. Results:The results of behavior assessment showed that there were significant differences in the motor stereotypic behavior and categorical stereotypic behavior score( F=270.9, 379.7, P<0.01), and the scores in WT+ IDPN group were higher than those in Tyrobp -/-+ IDPN group (motor stereotypic behavior: (3.23±0.26), (2.13±0.21), t=9.02, P<0.05; categorical stereotypic behavior: (45.80±4.29), (26.60±3.48), t=12.00, P<0.05). Western blot results showed that there were significant differences in the protein expression level of TNF-α, IL-6, IL-1β, TLR4, Myd88, p-NF-κB p65 and p-IκBα ( F=29.07, 23.09, 39.36, 57.6, 52.55, 15.50, 40.48, all P<0.05), the level of those in WT + IDPN group was higher than those in WT+ NS group( t=8.31, 7.37, 8.13, 11.43, 10.47, 6.05, 9.96, all P<0.05), Tyrobp -/-+ IDPN group was higher than Tyrobp -/-+ NS group ( t=3.60, 3.00, 5.84, 4.81, 3.59, 2.26, 4.68, all P<0.05), and WT + IDPN group was higher than Tyrobp -/-+ IDPN group ( t=3.97, 3.93, 4.14, 6.40, 7.63, 3.45, 3.03, all P<0.05). Immunofluorescence showed that microglial cells in the striatum region of mice in WT+ IDPN group and Tyrobp -/-+ IDPN group were enlarged and microglial cells were activated, and the activation pattern of microglial cells in WT+ IDPN group was more obvious than that in Tyrobp -/-+ IDPN group. Conclusion:Tyrobp may be involved in the pathogenesis of Tourette's syndrome by promoting neuroinflammation mediated by TLR4/Myd88/NF-κB signaling pathway.

Advances in the diagnosis of cutaneous malignant melanoma / 中国基层医药

Cutaneous malignant melanoma arises from the neural crest-derived melanocytes and is a highly malignant tumor with complex clinical and pathological manifestations. In recent years, its incidence rate is increasing gradually. It is one of the most common cutaneous malignant tumors. This paper reviews the advances of the diagnosis of cutaneous malignant melanoma.

Research progress and thinking on the metabolism of polysaccharide drugs in vivo and the key technology of PK/PD / 中国临床药理学与治疗学

Polysaccharide drugs are a type of safe and effective natural drug with a wide range of pharmacological activity such as anti-tumor, immunomodulation, and oxidation, and polysaccharide drugs are currently more concerned. However, since the molecular weight of the polysaccharide is quite large, most of which do not have ultraviolet absorption and fluorescent groups, which makes the qualitative and quantitative analysis of polysaccharides are relatively difficult. In addition, endogenous sugar substances may also cause certain interference to polysaccharide assay in biological samples, and therefore, in vivo metabolism and PK/PD key technologies in polysaccharide drugs have been research hotspots. This paper summarizes the relevant literature published in recent years, reviewing the biological activity and pharmacokinetics of polysaccharide drugs, proposing gut bacteria may be potential "organ" affecting metabolism and efficacy of polysaccharide drugs, and providing thoughts on gut bacteria mediating polysaccharide drugs in vivo and key technology research of PK/PD, in order to provide more scientific ideas for pharmacokinetics, pharmacological research and molecular mechanisms of polysaccharide drugs.

Research progress on sexual health care carried out by nurses / 中国实用护理杂志

Sexual health is an important part of the overall health of patients.The ability of nurses to carry out sexual health care directly affects the overall level of medical care. This article reviews the concepts of sexual health and sexual health care, the evaluation tools of sexual health care, the practical models and influencing factors of nurses' sexual health care, with a view to providing a reference for improving the practice level of nurses carrying out sexual health care.

Study of attention network of benign childhood epilepsy with centrotemporal spikes / 中华神经科杂志

Objective:To investigate whether children with benign childhood epilepsy with centrotemporal spikes (BECT) still have attention network damage and its correlative factors after complete remission.Methods:Thirty BECT patients over 16 years old and without seizures over two years (BECT group; 21 males, nine females, median age 17 years) in the Department of Neurology, Provincial Children′s Hospital Affiliated to Anhui Medical University from January 1, 2009 to December 31, 2010 and 42 healthy controls (control group; 30 males, 12 females, median age 17 years) from the First Affiliated Hospital of Anhui Medical University were tested by the attention network test tool.Results:There was not statistically significant difference in the accuracy rate and total reaction time of attention network test between the BECT group and the control group [97.0% (95.0%, 99.0%) vs 98.0% (95.5%, 98.0%), Z=-0.437, P=0.662; 587.50 (523.50, 668.75) ms vs 610.00 (584.25, 631.75) ms, Z=-0.320, P=0.749; respectively]. And there was not statistically significant difference in the efficiency of the alert network, directional network, and executive control network in the BECT group compared with the control group [(46.13±24.97) ms vs (48.52±27.65) ms, t=-0.376, P=0.708; (32.23±18.12) ms vs (33.21±19.68) ms, t=-0.215, P=0.830; (124.50±39.87) ms vs (117.60±50.13) ms, t=0.626, P=0.533; respectively]. The accuracy of attention network test was positively correlated with the age of onset ( b=0.925, P=0.012), and was negatively correlated with the total number of seizures ( b=-0.853, P=0.025). Conclusion:Although the accuracy of attention network test in BECT patients after remission was correlated with age of onset and total number of seizures, BECT patients had no attention network damage after complete remission compared with healthy controls.

Metformin inhibits pancreatic cancer metastasis caused by SMAD4 deficiency and consequent HNF4G upregulation

Pancreatic ductal adenocarcinoma (PDAC) has poor prognosis due to limited therapeutic options. This study examines the roles of genome-wide association study identified PDAC-associated genes as therapeutic targets. We have identified HNF4G gene whose silencing most effectively repressed PDAC cell invasiveness. HNF4G overexpression is induced by the deficiency of transcriptional factor and tumor suppressor SMAD4. Increased HNF4G are correlated with SMAD4 deficiency in PDAC tumor samples and associated with metastasis and poor survival time in xenograft animal model and in patients with PDAC (log-rank P = 0.036; HR = 1.60, 95% CI = 1.03-2.47). We have found that Metformin suppresses HNF4G activity via AMPK-mediated phosphorylation-coupled ubiquitination degradation and inhibits in vitro invasion and in vivo metastasis of PDAC cells with SMAD4 deficiency. Furthermore, Metformin treatment significantly improve clinical outcomes and survival in patients with SMAD4-deficient PDAC (log-rank P = 0.022; HR = 0.31, 95% CI = 0.14-0.68) but not in patients with SMAD4-normal PDAC. Pathway analysis shows that HNF4G may act in PDAC through the cell-cell junction pathway. These results indicate that SMAD4 deficiency-induced overexpression of HNF4G plays a critical oncogenic role in PDAC progression and metastasis but may form a druggable target for Metformin treatment.

Etomidate reduces excitability of the neurons and suppresses the function of nAChR ventral horn in the spinal cord of neonatal rats / 南方医科大学学报

OBJECTIVE@#To investigate the effects of etomidate on electrophysiological properties and nicotinic acetylcholine receptors (nAChRs) of ventral horn neurons in the spinal cord.@*METHODS@#The spinal cord containing lumbosacral enlargement was isolated from 19 neonatal SD rats aged 7-12 days. The spinal cord were sliced and digested with papain (0.18 g/30 mL artificial cerebrospinal fluid) and incubated for 40 min. At the ventral horn, acute mechanical separation of neurons was performed with fire-polished Pasteur pipettes, and perforated patch-clamp recordings combined with pharmacological methods were employed on the adherent healthy neurons. In current-clamp mode, the spontaneous action potential (AP) of the ventral horn neurons in the spinal cord was recorded. The effects of pretreatment with different concentrations of etomidate on AP recorded in the ventral horn neurons were examined. In the voltage-clamp mode, nicotine was applied to induce inward currents in the ventral horn neurons, and the effect of pretreatment with etomidate on the inward currents induced by nicotine were examined with different etomidate concentrations, different holding potentials and different use time.@*RESULTS@#The isolated ventral horn neurons were in good condition with large diverse somata and intact processes. The isolated spinal ventral horn neurons (=21) had spontaneous action potentials, and were continuously perfused for 2 min with 0.3, 3.0 and 30.0 μmol/L etomidate. Compared with those before administration, the AP amplitude, spike potential amplitude and overshoot were concentration-dependently suppressed ( < 0.01), and spontaneous discharge frequency was obviously reduced ( < 0.01, =12). The APs of the other 9 neurons were completely abolished by etomidate at 3.0 or 30 μmol/L. At the same holding potential (VH=-70 mV), pretreatment with 0.3, 3.0 or 30.0 μmol/L etomidate for 2 min concentration-dependently suppressed the current amplitude induced by 0.4 mmol/L nicotine ( < 0.01, =7). At the holding potentials of - 30, - 50, and - 70 mV, pretreatment with 30.0 μmol/L etomidate for 2 min voltage-dependently suppressed the current amplitude induced by 0.4 mmol/L nicotine ( < 0.01, =6 for each holding potential). During the 6 min of 30.0 μmol/L etomidate pretreatment, the clamped cells were exposed to 0.4 mmol/L nicotine for 4 times at 0, 2, 4, and 6 min (each exposure time was 2 s), and the nicotinic current amplitude decreased gradually as the number of exposures increased. But at the same concentration, two nicotine exposures (one at the beginning and the other at the end of the 6 min pretreatment) resulted in a significantly lower inhibition rate compared with 4 nicotine exposures ( < 0.01, =6).@*CONCLUSIONS@#etomidate reduces the excitability of the spinal ventral neurons in a concentration-dependent manner and suppresses the function of nAChR in a concentration-, voltage-, and use-dependent manner.

Beh?et's disease complicated with tendinopathy: report of 2 cases with literature review / 中华风湿病学杂志

Objective:To explore the possible related factors of Beh?et's disease complicated with tendinitis, in order to better understand the etiology and development mechanism so to guide clinical diagnosis and treatment.Methods:The clinical data of patients with Beh?et's disease complicated with tendonitis treated at Department of Rheumatology and Immunology of Lanzhou University Second Hospital from October 2018 to September 2019 were retrospectively reviewed and related literature were reviewed.Results:Two patients were diagnosed as Beh?et's disease. Foot pain occurred during the treatment. Ultrasound showed tendonitis, and the corresponding treatment relieved the symptoms.Conclusion:Tendons may be involved and presents as a chronic change in patients with Beh?et's disease. In patients with rheumatic diseases, attention should be paid to the correlation between the disease and tendonitis. Aggressive treatment can prevent adverse consequences.