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Kai-Xin-San consists of Ginseng Radix, Polygalae Radix, Acori Tatarinowii Rhizoma, and Poria at a ratio of 3:3:2:2. Kai-Xin-San has been widely used for the treatment of emotional disorders in China. However, no studies have identified the key proteins implicated in response to Kai-Xin-San treatment. In this study, rat models of chronic mild stress were established using different stress methods over 28 days. After 14 days of stress stimulation, rats received daily intragastric administrations of 600 mg/kg Kai-Xin-San. The sucrose preference test was used to determine depression-like behavior in rats, while isobaric tags were used for relative and absolute quantitation-based proteomics to identify altered proteins following Kai-Xin-San treatment. Kai-Xin-San treatment for 2 weeks noticeably improved depression-like behaviors in rats with chronic mild stress. We identified 33 differentially expressed proteins: 7 were upregulated and 26 were downregulated. Functional analysis showed that these differentially expressed proteins participate in synaptic plasticity, neurodevelopment, and neurogenesis. Our results indicate that Kai-Xin-San has an important role in regulating the key node proteins in the synaptic signaling network, and are helpful to better understand the mechanism of the antidepressive effects of Kai-Xin-San and to provide objective theoretical support for its clinical application. The study was approved by the Ethics Committee for Animal Research from the Chinese PLA General Hospital (approval No. X5-2016-07) on March 5, 2016.

Adrenomedullin, a peptide with multiple physiological functions in nervous system injury and disease, has aroused the interest of researchers. This review summarizes the role of adrenomedullin in neuropathological disorders, including pathological pain, brain injury and nerve regeneration, and their treatment. As a newly characterized pronociceptive mediator, adrenomedullin has been shown to act as an upstream factor in the transmission of noxious information for various types of pathological pain including acute and chronic inflammatory pain, cancer pain, neuropathic pain induced by spinal nerve injury and diabetic neuropathy. Initiation of glia-neuron signaling networks in the peripheral and central nervous system by adrenomedullin is involved in the formation and maintenance of morphine tolerance. Adrenomedullin has been shown to exert a facilitated or neuroprotective effect against brain injury including hemorrhagic or ischemic stroke and traumatic brain injury. Additionally, adrenomedullin can serve as a regulator to promote nerve regeneration in pathological conditions. Therefore, adrenomedullin is an important participant in nervous system diseases.

Background: The present study aimed to investigate the drug-drug interaction and initial dosage optimization of aripiprazole in patients with schizophrenia based on population pharmacokinetics. Research design and methods: A total of 119 patients with schizophrenia treated with aripiprazole were included to build an aripiprazole population pharmacokinetic model using nonlinear mixed effects. Results: The weight and concomitant medication of fluoxetine influenced aripiprazole clearance. Under the same weight, the aripiprazole clearance rates were 0.714:1 in patients with or without fluoxetine, respectively. In addition, without fluoxetine, for the once-daily aripiprazole regimen, dosages of 0.3 and 0.2 mg kg-1 day-1 were recommended for patients with schizophrenia weighing 40-95 and 95-120 kg, respectively, while for the twice-daily aripiprazole regimen, 0.3 mg kg-1 day-1 was recommended for those weighing 40-120 kg. With fluoxetine, for the once-daily aripiprazole regimen, a dosage of 0.2 mg kg-1 day-1 was recommended for patients with schizophrenia weighing 40-120 kg, while for the twice-daily aripiprazole regimen, 0.3 and 0.2 mg kg-1 day-1 were recommended for those weighing 40-60 and 60-120 kg, respectively. Conclusion: This is the first investigation of the effects of fluoxetine on aripiprazole via drug-drug interaction. The optimal aripiprazole initial dosage is recommended in patients with schizophrenia. [ABSTRACT FROM AUTHOR]

Metallic glasses (MGs) are metal alloys with attractive properties for use as electrodes in strain sensors, such as high conductivity, mechanical strength, and strong corrosion resistance owing to their unique amorphous atomic arrangements, which are critical criteria for highly reliable sensors. However, MGbased strain sensors that may detect strains of >1% with high gauge factors have not yet been reported. In this study, an AlY-MG thin film in an amorphous phase is successfully deposited on a target substrate via sputter deposition. Whereas layer-by-layer-assembled graphene nanoplatelets (GNP) enable stable strain sensing over an extended range, the amorphous atomic arrangement of the MG film resulted in more distinct changes in electron conducting path under strains from 2% to 10%, which is induced by cracks initiated on the surface of the AlY film. Furthermore, the chemical stability of the sputtered AlY thin film is examined via electrical and optical analyses, which prove the high chemical stability at the interface between AlY and the GNP layer. As a result, a strain sensor based on the AlY film, which may detect various human motions when adhered to the skin, is developed. [ABSTRACT FROM AUTHOR]

The landscape of current tumor treatment has been revolutionized by the advent of immunotherapy based on PD-1/PD-L1 inhibitors. Leveraging its capacity to mobilize systemic antitumor immunity, which is primarily mediated by T cells, there is growing exploration and expansion of its potential value in various stages of clinical tumor treatment. Neoadjuvant immunotherapy induces a robust immune response against tumors prior to surgery, effectively facilitating tumor volume reduction, early eradication or suppression of tumor cell activity, and control of potential metastatic spread, to improve curative surgical resection rates, and prevent tumor recurrence. This review delineates the theoretical basis of neoadjuvant immunotherapy from preclinical research evidence, discusses specific challenges in clinical application, and provides a comprehensive overview of clinical research progress in neoadjuvant immunotherapy for gastrointestinal tumors. These findings suggest that neoadjuvant immunotherapy has the potential to ameliorate immunosuppressive states and enhance cytotoxic T cell function while preserving lymphatic drainage in the preoperative period. However, further investigations are needed on specific treatment regimens, suitable patient populations, and measurable endpoints. Despite numerous studies demonstrating the promising efficacy and manageable adverse events of neoadjuvant immunotherapy in gastrointestinal tumors, the availability of high-quality randomized controlled trials is limited, which highlights the necessity for further research. [ABSTRACT FROM AUTHOR]

In the face of the unprecedented public health crisis caused by the novel coronavirus pneumonia epidemic, front-line health workers are under enormous mental pressure. This paper aims to explore the mental health challenges faced by front-line health workers in the early stages of a public health emergency, such as stress, anxiety, and depression. At the same time, the factors that increase their mental stress are analyzed, and practical measures are put forward to prevent and manage mental health problems, aiming at improving the quality of medical treatment during public health emergencies. This paper has some reference value for people engaged in mental health prevention. [ABSTRACT FROM AUTHOR]

ABSTRACT: The Narooma-Batemans Bay (NBB) area along the southeast coast of Australia is a part of the eastern zone of the Early Paleozoic Lachlan Orogen. In the NBB, a set of rock association consisting of turbidites, siliceous rock, basic lava, and argillaceous melange zone is mainly developed. According to systematic field geological survey, the deformation of 3 stages (D1, D2, and D3) was identified in the NBB. At stage D1, with the original bedding S0 in a nearly east-west trending as the deformation plane, tight folds, isoclinal folds, and other structures formed in the NBB accompanied by structural transposition. As a result, crenulation cleavage developed along the axial plane of the folds and schistosity S1 formed. At stage D2, with north-south-trending schistosity S1 as the deformation plane, a large number of asymmetrical folds and rotated porphyroclasts formed owing to thrusting and shear. At stage D3, left-lateral strike-slip occurred along the main north-south-trending schistosity. Based on the analysis of the characteristics of tectonic deformation in the NBB and summary of previous research results, it is determined that the early-stage (D1) deformation is related to Ordovician Macquarie arc-continent collision and the deformation at stages D2 and D3 is the result of the westward subduction of Paleo-Pacific Plate. That is, it is not the continuous westward subduction of the Paleo-Pacific Plate that constitutes the evolution model of the NBB as previously considered.

Abstract Background Plant secondary metabolites and phytochemicals that exhibit strong bioactivities have potential to be developed as safe and efficient natural antimicrobials against food contamination and addressing antimicrobial resistance caused by the overuse of chemical synthetic preservative. In this study, the chemical composition, antibacterial activities and related mechanism of the extracts of the valonia and the shell of Quercus variabilis Blume were studied to determine its potential as a safe and efficient natural antimicrobial. Methods The phenolic compositions of valonia and shell extracts were determined by folin-ciocalteau colourimetric method, sodium borohydride/chloranil-based assay and the aluminium chloride method and then further identified by the reverse-phase HPLC analysis. The antibacterial activities of valonia and shell extracts were evaluated by the agar disk diffusion method and agar dilution method. The related antibacterial mechanism was explored successively by the membrane of pathogens effect, phosphorous metabolism, whole-cell proteins and the microbial morphology under scanning electron microscopy. Results The n-butanol fraction and water fraction of valonia along with n-butanol fraction of the shell contains enrich phenolics including ellagic acid, theophylline, caffeic acid and tannin acid. The n-butanol fraction and ethanol crude extracts of valonia exhibited strong antibacterial activities against Salmonella paratyphi A (S. paratyphi A) and Staphylococcus aureus (S. aureus) with the DIZ values ranged from 10.89 ± 0.12 to 15.92 ± 0.44, which were greater than that of the Punica granatum (DIZ: 10.22 ± 0.18 and 10.30 ± 0.21). The MIC values of the n-butanol fraction and ethanol crude extracts of valonia against S. paratyphi A and S. aureus were 1.25 mg/ml and 0.625 mg/ml. The related antibacterial mechanism of n-butanol fraction and ethanol crude extracts of valonia may be attributed to their strong impact on membrane permeability and cellular metabolism. Those extracts exhibited strong antibacterial activity according to inhibit the synthesis of bacterial proteins and seriously change morphological structure of bacterial cells. Conclusions The n-butanol fraction and ethanol crude extracts of valonia had reasonably good antibacterial activities against S. paratyphi A and S. aureus. This study suggests possible application of valonia and shell as natural antimicrobials or preservatives for food and medical application.

Abstract. Objective:. To investigate thyroid-stimulating hormone (TSH) levels and thyroid peroxidase antibody (TPOAb) in early pregnancy and to estimate the risk of development of gestational diabetes mellitus (GDM). Methods:. The levels of TSH, free thyroxine, free triiodothyronine, and TPOAb were retrospectively evaluated in 2333 pregnant women. All women recruited were divided into groups of TSH high (H), TSH low (L), TSH (H) TPOAb positive (+), TSH (H)TPOAb negative (−), TSH normal (N)TPOAb (+), TSH (L)TPOAb (+), TSH (L)TPOAb (−), and estimated the risk of GDM. Results:. TSH level (X2 = 13.0024, P = 0.0015) and TSH combined TPOAb (X2 = 20.0038, P = 0.0012) were correlated to development of GDM. The level of TSH in 95 women was increased, and in 216 women were decreased. Of the 2333 pregnant women, 546 patients were diagnosed with GDM, with a prevalence of 23.40%. The prevalence of GDM was 35.78% and 28.70% for the TSH high (H) and TSH low (L) pregnant women, respectively. The increased TSH (P = 0.0013, odds ratio: 2.09, confidence interval:1.34–3.28) was correlated to increase GDM incidence. TSH (H) TPOAb (+) (n = 29), TSH (H) TPOAb (−) (n = 58), TSH normal (N) TPOAb (+) (n = 265), TSH (L) TPOAb (+) (n = 30), TSH (L) TPOAb (−) (n = 154) were in this study. The prevalence of GDM was 51.72%, 29.31%, 23.02%, 26.67%, and 29.87% for the TSH (H) TPOAb (+), TSH (H) TPOAb (−), TSH (N) TPOAb (+), TSH (L) TPOAb (+), and TSH (L) TPOAb (−) pregnant women, respectively. Only the TSH (H) TPOAb (+) pregnant women had a significant higher incidence of GDM (P = 0.0018, odds ratio: 3.63, confidence interval: 1.62–8.16). Trimester specific results showed that only second trimester had higher GDM risk either analyze TSH or the combination of TSH and TPOAb. Conclusion:. Elevated TSH level and TPOAb positive in the second trimester of pregnancy were correlated to an increased risk of GDM.

Abstract Background Ultrasound-guided lateral transversus abdominis plane (TAP) block can provide definite analgesia to the anterior abdominal wall. However, whether this method is useful in renal surgery through the lateral abdominal wall pathway remains unknown. The study aimed to evaluate the analgesic efficacy of lateral TAP block for retroperitoneoscopic partial or radical nephrectomy. Method In this prospective, randomized, double-blind, placebo-controlled trial, eligible patients were randomized into two groups. After anaesthesia induction, ultrasound-guided lateral TAP block was performed with either 30 ml of 0.4% ropivacaine (Group T) or an equivalent volume of normal saline (Group C). The primary outcomes were opioid consumption during surgery and in the first 24 h after surgery. Secondary outcomes included postsurgical pain intensity immediately awakening from anaesthesia and at 0.5, 1, 2, 6, 12, and 24 h after surgery, as well as recovery variables including the incidence of postoperative nausea and vomiting (PONV), sleep quality, time to first ambulation, drainage and length of hospital stay. Results A total of 104 patients were enrolled and randomized (53 in Group T and 51 in Group C). Laparoscopic surgery was converted to open surgery in one patient of Group T; this patient was excluded from the outcome analysis. The opioid consumption during surgery (intravenous morphine equivalent dose: median 35.0 mg [interquartile range 18.0, 49.6] in Group C vs. 40.3 mg [20.9, 59.0] in Group T, P = 0.281) and in the first 24 h after surgery (10.8 mg [7.8, 21.7] in Group C vs. 13.2 mg [8.0, 26.6] in Group T, P = 0.311) did not differ significantly between groups. There were no significant differences between groups regarding the pain intensity at all time points after surgery and the recovery variables (all P > 0.05). Conclusions Our results showed that, in patients undergoing retroperitoneoscopic renal surgery, preoperative lateral TAP did not decrease intra- and postoperative opioid consumption, nor did it relieve pain intensity or promote postoperative recovery in the first 24 h after surgery. However, the trial might be underpowered. Trial registration This study was registered on November 4, 2017, in the Chinese Clinical Trail Registry with the identification number ChiCTR-INR-17013244.

Abstract In this paper, an anomalous spectral data of distributed Bragg reflector (DBR) quantum cascade lasers (QCLs) emitting around 7.6 μm is presented. The two-section DBR lasers, consisting of a gain section and an unpumped Bragg reflector, display an output power above 0.6 W in continuous wave (CW) mode at room temperature. The anomalous spectral data is defined as a longitudinal mode which moves toward shorter wavelengths with increasing temperature or injection current, which is unexpected. Although the longer wavelength modes are expected to start lasing when raising device temperature or injection current, occasional mode hops to a shorter wavelength are seen. These anomalous mode transitions are explained by means of modal analysis. The thermal-induced change of the refractive index implied by an increase in the temperature or injection current yields nearly periodic transitions between cavity modes.

Abstract Background Acute kidney injury (AKI) is a common complication following non-cardiac surgery with adverse short- and long- term morbidity and mortality. Evidence shows that hypoalbuminemia is associated with increased AKI risk in patients with infectious diseases and cancer and following cardiac surgery and transplant surgery. However, little evidence is available on non-cardiac surgery population. Thus, we investigated the association between preoperative hypoalbuminemia and AKI following non-cardiac surgery. Methods We retrospectively assessed perioperative risk factors and preoperative serum albumin concentration in 729 consecutive adult patients who underwent non-cardiac surgery from July 1, 2017, to June 30, 2018. Each patient was categorized according to maximal Kidney Disease Improving Global Outcomes criteria based on creatinine changes and urine output within the first week after surgery. Multivariate Logistic regression models were used to analyze the association between preoperative hypoalbuminemia and postoperative AKI. Results Of 729 patients, 188 (25.8%) developed AKI. AKI incidence was higher in patients with preoperative serum albumin

AIM: To investigate the phenotype and genotype of a family with X-linked recessive Lowe syndrome. METHODS: All the members in the Chinese pedigree underwent comprehensive ophthalmologic and systemic examinations. Genomic DNA was isolated from peripheral blood of the pedigree members and 100 unrelated healthy Chinese subjects. Direct sequencing was performed to screen the exons and intron boundaries of OCRL. RESULTS: The ophthalmological and systemic examinations suggested that the affected individual had Lowe syndrome. The phenotype in the pedigree is severe and consistent among all the affected individuals except for an individual who additionally suffered from congenital heart disease and laryngeal cartilage dysplasia. Directional Sanger sequencing identified a complex mutation c.(2368_2368delG; c.2370A>C) in the Rho-GTPase activating protein domain. This complex mutation causes termination of protein synthesis at amino acid 824 and result in a new peptide with 823 amino acids (p.Ala790ProfsX34). This mutation was not detected in 100 unrelated healthy Chinese subjects. CONCLUSION: Our findings expand the phenotypic and genotypic spectrum of Lowe syndrome.

Abstract Background The purpose of this multicentre, retrospective study was to evaluate the safety and efficacy of different surgical approaches for treating thoracolumbar tuberculosis. Methods This study reviewed 132 patients with thoracolumbar tuberculosis in six institutions between January 1999 and January 2015 surgically treated by an anterior-only approach (n = 22, group A), an anterior combined with posterior approach (n = 79, group B), and a posterior-only approach (n = 31, group C). All patients were treated with standard antituberculosis drugs pre- and postoperatively and were followed regularly after surgery. Clinical symptoms, nerve function, and the erythrocyte sedimentation rate were observed, and kyphosis correction and bone fusion were evaluated by X-ray or computed tomography. Results At the last follow-up, all patients had achieved bone fusion, relief from pain, and neurological recovery. The Cobb angle was improved; however, the Cobb angle showed a degree of loss at the final follow-up after all three surgical approaches. Further comparisons revealed a difference in angle loss at the final follow-up among the three groups; groups B and C were superior to group A in maintenance of the correction. The posterior-only approach was characterized by a shorter operative time and reduced blood loss. Conclusions Surgery by a posterior-only approach is superior to that by an anterior-only approach and anterior combined with posterior approach in terms of permanent kyphosis correction and spinal stability maintenance. Therefore, we recommend surgery by a posterior-only approach as the optimized treatment for thoracolumbar tuberculosis if the indications for this treatment are met.

Abstract Background Extracorporeal membrane oxygenation offers temporary hemodynamic support for patients with refractory cardiogenic shock after cardiovascular surgery. However, the initiation time for such patients is controversial. Changing the initiation time might improve the outcomes. This study aimed to investigate whether early extracorporeal membrane oxygenation could improve postoperative outcomes in patients at a high risk of cardiogenic shock. Methods In this retrospective study, 173 patients with cardiovascular diseases at a high risk of refractory cardiogenic shock which assessed via empirical risk evaluation from 2010 to 2017 were included. After propensity matching, 36 patients, who were matched to patients initiated with extracorporeal membrane oxygenation after cardiovascular operation (delayed extracorporeal membrane oxygenation group, n = 36), were also initiated with such early in the operating room (early extracorporeal membrane oxygenation group, n = 36). The primary outcome was death. The secondary outcomes included receiving continuous renal replacement therapy, ventricular arrhythmia, and pulmonary infection. Results The demographic and baseline variables were similar between the matched groups. The early extracorporeal membrane oxygenation group showed lower mortality (69.44% vs 41.67%, P = 0.03), pulmonary infection morbidity (86.11% vs 55.56%, P

Background: Dysregulation of immune checkpoint molecules leads to immune evasion in human tumours but has become a viable target for tumour therapy. Here, we examined expression of Herpes virus entry mediator (HVEM), an immune checkpoint molecule, in human glioblastoma (GBM) to assess its potential as a molecular target for treatment. Methods: Molecular and clinical data from publicly available genomic databases containing WHO grade II-IV human glioma cases (n = 1866) were analyzed. Immunohistochemistry was applied to assess HVEM protein levels in primary tumour sections. Statistical analysis was performed using Matlab and R language. Findings: HVEM was found to be elevated in aggressive gliomas, particularly in the mesenchymal and isocitrate dehydrogenase (IDH) wild-type molecular subtypes of GBM. HVEMhigh tumours tended to be associated with amplification of EGFR and loss of PTEN, while HVEMlow tumours harbored mutations in IDH1 (93%). HVEM exhibited potential as a prognostic marker based on Cox regression and nomogram models. HVEM displayed intra-tumour heterogeneity and was more highly expressed in peri-necrotic and microvascular regions. Gene ontology and pathway analysis revealed enrichment of HVEM in multiple immune regulatory processes, such as suppression of T cell mediated immunity in GBM. Finally, in cell lineage analysis, HVEM was found to be tightly associated with several infiltrating immune and stromal cell types which localized to the tumour microenvironment. Interpretation: Our data highlights the importance of HVEM in the development of GBM and as a potential molecular target in combination with current immune checkpoint blockades for treatment of GBM. Keywords: Glioma, HVEM, Immune response, Prognosis, Tumour microenvironment

Summary: Aryl–heteroatom (C–X) bonds ubiquitously exist in organic, medicinal, and material chemistry, but a universal method to construct diverse C–X bonds is lacking. Here we report our discovery of a convenient and efficient approach to construct various C–X bonds using arylammonium salts as the substrate via an SNAr process. This strategy features mild reaction condition, no request of transition metal catalyst, and easy formation of various C–X bonds (C–S, C–Si, C–Sn, C–Ge, C–Se, C–N). The method was successfully applied to a late-stage functionalization of an existing antibiotic drug, to a Clickable reaction of NBD-based ammonium salt as turn-on fluorescent probe to recognize L-cysteine and homocysteine, and to the synthesis of a DNA encoded library (DEL) bearing different C–X bonds. : Organic Chemistry; Organic Synthesis; Chemical Reaction Engineering Subject Areas: Organic Chemistry, Organic Synthesis, Chemical Reaction Engineering

Abstract Background Metabolic disturbances have been correlated with suicidality, but little is known about the association between suicide risk and metabolic disturbances among individuals with depression. This study was to evaluate the prevalence and clinical correlations, especially cardio-metabolic associated factors of recent suicide attempts in Chinese patients with major depressive disorder (MDD). Methods A total of 288 MDD inpatients were recruited. Their clinical and demographic data together with plasma glucose, lipid and thyroid function parameters were collected. Self-Rating Depression Scale (SDS), Self-Rating Anxiety Scale (SAS) and Eysenck Personality Questionnaire (EPQ) were rated for most of the patients. Results Of these MDD inpatients, 20.14% had attempted suicide during the past 1 month. Compared to those who had not attempted suicide, the suicide attempters had a significantly longer duration of illness, lower low-density lipoprotein (LDL) cholesterol, lower total cholesterol, and more psychotic symptoms. However, all these significant results did not survive after the bonferroni correction (all p > 0.05). A logistic regression analysis indicated that suicide attempts were associated with the lower total cholesterol and more psychotic symptoms. Conclusions Our findings support the hypothesis of the association of low plasma cholesterol level and recent suicidal attempts in patients with MDD.

Abstract High-power, low-threshold stable single-mode operation buried distributed feedback quantum cascade laser by incorporating sampled grating emitting at λ ~ 4.87 μm is demonstrated. The high continuous wave (CW) output power of 948 mW and 649 mW for a 6-mm and 4-mm cavity length is obtained at 20 °C, respectively, which benefits from the optimized optical field distribution of sampled grating. The single-mode yields of the devices are obviously enhanced by controlling cleaved positions of the two end facets precisely. As a result, stable single-mode emission and mode tuning linearly without any mode hopping of devices are obtained under the different heat sink temperatures or high injection currents.

Growth differentiation factor 11 (GDF11) is a member of the transforming growth factor β superfamily that alleviates cardiac hypertrophy, myocardial infarction, and vascular injury by regulating oxidative stress, inflammation, and cell survival. However, the roles and underlying mechanisms of GDF11 in diabetic cardiomyopathy (DCM) remain largely unknown. In this study, we sought to determine whether GDF11 could prevent DCM. After establishing a mouse model of diabetes by administering a high-fat diet and streptozotocin, intramyocardial injection of an adeno-associated virus was used to achieve myocardium-specific GDF11 overexpression. GDF11 remarkably improved cardiac dysfunction and interstitial fibrosis by reducing the levels of reactive oxygen species and protecting against cardiomyocyte loss. Mechanistically, decreased sirtuin 1 (SIRT1) expression and activity were observed in diabetic mice, which was significantly increased after GDF11 overexpression. To further explore how SIRT1 mediates the role of GDF11, the selective inhibitor EX527 was used to block SIRT1 signaling pathway, which abolished the protective effects of GDF11 against DCM. In vitro studies confirmed that GDF11 protected against H9c2 cell injury in high glucose and palmitate by attenuating oxidative injury and apoptosis, and these effects were eliminated by SIRT1 depletion. Our results demonstrate for the first time that GDF11 protects against DCM by regulating SIRT1 signaling pathway.