Immune signatures predict response to house dust mite subcutaneous immunotherapy in patients with allergic rhinitis.

BACKGROUND: Identifying predictive biomarkers for allergen immunotherapy response is crucial for enhancing clinical efficacy. This study aims to identify such biomarkers in patients with allergic rhinitis (AR) undergoing subcutaneous immunotherapy (SCIT) for house dust mite allergy. METHODS: The Tongji (discovery) cohort comprised 72 AR patients who completed 1-year SCIT follow-up. Circulating T and B cell subsets were characterized using multiplexed flow cytometry before SCIT. Serum immunoglobulin levels and combined symptom and medication score (CSMS) were assessed before and after 12-month SCIT. Responders, exhibiting ≥30% CSMS improvement, were identified. The random forest algorithm and logistic regression analysis were used to select biomarkers and establish predictive models for SCIT efficacy in the Tongji cohort, which was validated in another Wisco cohort with 43 AR patients. RESULTS: Positive SCIT response correlated with higher baseline CSMS, allergen-specific IgE (sIgE)/total IgE (tIgE) ratio, and frequencies of Type 2 helper T cells, Type 2 follicular helper T (TFH 2) cells, and CD23+ nonswitched memory B (BNSM ) and switched memory B (BSM ) cells, as well as lower follicular regulatory T (TFR ) cell frequency and TFR /TFH 2 cell ratio. The random forest algorithm identified sIgE/tIgE ratio, TFR /TFH 2 cell ratio, and BNSM frequency as the key biomarkers discriminating responders from nonresponders in the Tongji cohort. Logistic regression analysis confirmed the predictive value of a combination model, including sIgE/tIgE ratio, TFR /TFH 2 cell ratio, and CD23+ BSM frequency (AUC = 0.899 in Tongji; validated AUC = 0.893 in Wisco). CONCLUSIONS: A T- and B-cell signature combination efficiently identified SCIT responders before treatment, enabling personalized approaches for AR patients.

Efficacy of the spirit-regulation method of Jin's three-needle therapy for post-stroke anxiety and its effect on the hypothalamus-pituitary-adrenal axis. / 靳三针调神针法治疗卒中后焦虑的疗效观察及对下丘脑-垂体-è‚¾ä¸Šè ºè½´çš„å½±å“.

OBJECTIVES: To observe the clinical efficacy of the spirit-regulation method of Jin's three-needle therapy on post-stroke anxiety and its effects on the hypothalamus-pituitary-adrenal (HPA) axis. METHODS: Fifty-four patients with post-stroke anxiety were divided into spirit regulation (Jin's three needle therapy) group and sham-acupuncture group according to the random number table method, 28 cases in the spirit regulation and 26 cases in the sham-acupuncture group. The patients of the two groups received the same regimen of basic medication and rehabilitation, and the same acupoint prescription was adopted, including Sishenzhen (extra points, 1.5 cun to Baihui ［GV20］ at 3, 6, 9 and 12 o'clock positions), Shenting (GV24), Yintang (EX-HN3), and bilateral Shenmen (HT7), Sanyinjiao (SP6), Hegu (LI4) and Taichong (LR3). The true acupuncture was delivered in the spirit regulation group and the sham acupuncture operated in the sham-acupuncture group. One treatment lasted for 30 min, once daily, 5 times a week. The duration of treatment was 3 weeks in the trial. Before treatment and on day 10 and day 21 of treatment, the changes in the score of Hamilton anxiety scale (HAMA) and that of National Institutes of Health Stroke Scale (NIHSS) were compared between the two groups separately. Using ELISA, the contents of adrenocorticotropin (ACTH) and cortisol (CORT) in the serum were detected, and the adverse reactions were recorded. RESULTS: In the within-group comparison before and after treatment, HAMA score and NIHSS score dropped on day 10 and day 21 after treatment in the spirit regulation group (P<0.05)；HAMA score and NIHSS score in the sham-acupuncture group were decreased on day 21 of treatment (P<0.05). After 21 days of treatment, HAMA score and NIHSS score in the spirit-regulation group were decreased significantly than those in the sham-acupuncture group (P<0.05) and the contents of ACTH and CORT in the serum decreased when compared with those before treatment and those of the sham-operation group (P<0.05). No obvious adverse events occurred in the spirit-regulation group and the sham-acupuncture group. CONCLUSIONS: Using sham acupuncture as a control, it is preliminarily confirmed that the spirit regulation method of Jin's three-needle therapy is effective on post-stroke anxiety. In association of the downtrend of serological indicators, it is speculated that the underlying mechanism of this therapy is related to HPA axis.

Comprehensive metabolome characterization and comparison between two sources of Dragon's blood by integrating liquid chromatography/mass spectrometry and chemometrics.

Dragon's Blood (DB) serves as a precious Chinese medicine facilitating blood circulation and stasis dispersion. Daemonorops draco (D. draco; Qi-Lin-Jie) and Dracaena cochinchinensis (D. cochinchinenesis; Long-Xue-Jie) are two reputable plant sources for preparing DB. This work was designed to comprehensively characterize and compare the metabolome differences between D. draco and D. cochinchinenesis, by integrating liquid chromatography/mass spectrometry and untargeted metabolomics analysis. Offline two-dimensional liquid chromatography/ion mobility-quadrupole time-of-flight mass spectrometry (2D-LC/IM-QTOF-MS), by utilizing a powerful hybrid scan approach, was elaborated for multicomponent characterization. Configuration of an XBridge Amide column and an HSS T3 column in offline mode exhibited high orthogonality (A0 0.80) in separating the complex components in DB. Particularly, the hybrid high-definition MSE-high definition data-dependent acquisition (HDMSE-HDDDA) in both positive and negative ion modes was applied for data acquisition. Streamlined intelligent data processing facilitated by the UNIFI™ (Waters) bioinformatics platform and searching against an in-house chemical library (recording 223 known compounds) enabled efficient structural elucidation. We could characterize 285 components, including 143 from D. draco and 174 from D. cochinchinensis. Holistic comparison of the metabolomes among 21 batches of DB samples by the untargeted metabolomics workflows unveiled 43 significantly differential components. Separately, four and three components were considered as the marker compounds for identifying D. draco and D. cochinchinenesis, respectively. Conclusively, the chemical composition and metabolomic differences of two DB resources were investigated by a dimension-enhanced analytical approach, with the results being beneficial to quality control and the differentiated clinical application of DB.

Integrated analysis of comorbidity, pregnant outcomes, and amniotic fluid cytogenetics of fetuses with persistent left superior vena cava.

BACKGROUND: Persistent left superior vena cava (PLSVC) is the most common venous system variant. The clinical characteristics and amniotic fluid cytogenetics of fetuses with PLSVC remain to be further explored. AIM: To develop reliable prenatal diagnostic recommendations through integrated analysis of the clinical characteristics of fetuses with PLSVC. METHODS: Cases of PLSVC diagnosed using prenatal ultrasonography between September 2019 and November 2022 were retrospectively studied. The clinical characteristics of the pregnant women, ultrasonic imaging information, gestational age at diagnosis, pregnancy outcomes, and amniocentesis results were summarized and analyzed using categorical statistics and the chi-square test or Fisher's exact test. RESULTS: Of the 97 cases diagnosed by prenatal ultrasound, 49 (50.5%) had isolated PLSVC and 48 (49.5%) had other structural abnormalities. The differences in pregnancy outcomes and amniocentesis conditions between the two groups were statistically significant (P < 0.05). No significant differences were identified between the two groups in terms of advanced maternal age and gestational age (P > 0.05). According to the results of the classification statistics, the most common intracardiac abnormality was a ventricular septal defect and the most common extracardiac abnormality was a single umbilical artery. In the subgroup analysis, the concurrent combination of intra- and extracardiac structural abnormalities was a risk factor for adverse pregnancy outcomes (odds ratio > 1, P < 0.05). Additionally, all abnormal cytogenetic findings on amniocentesis were observed in the comorbidity group. One case was diagnosed with 21-trisomy and six cases was diagnosed with chromosome segment duplication. CONCLUSION: Examination for other structural abnormalities is strongly recommended when PLSVC is diagnosed. Poorer pregnancy outcomes and increased amniocentesis were observed in PLSVC cases with other structural abnormalities. Amniotic fluid cytogenetics of fetuses is recommended for PLSVC with other structural abnormalities.

Effects of ultrasound monitoring of gastric residual volume on feeding complications, caloric intake and prognosis of patients with severe mechanical ventilation.

BACKGROUND: Monitoring of gastric residual is an important approach for assessing gastric emptying in patients with mechanical ventilation. By monitoring gastric contents, the enteral nutrition scheme can be adjusted in time to ensure feeding safety. AIM: To investigate the effects of ultrasound monitoring on the incidence of feeding complications, daily caloric intake and prognosis of patients with severe mechanical ventilation. To analyze the clinical significance of ultrasound monitoring of gastric residual volume (GRV) up to 250 mL to provide a theoretical basis for clinical practice. METHODS: Patients admitted to the department of emergency medicine of the Affiliated Hospital of Nantong University from January 2018 to June 2022 who received invasive mechanical ventilation and continuous enteral nutrition support within 24-48 h after admission were enrolled in this study. Medical records for patients within 7 d of hospitalization were retrospectively analyzed to compare the incidence of feeding complications, daily caloric intake and clinical prognosis between patients with gastric residual ≥ 250 mL and < 250 mL, as monitored by ultrasound on the third day. RESULTS: A total of 513 patients were enrolled in this study. Incidences of abdominal distension, diarrhea, and vomiting in the < 250 mL and ≥ 250 mL groups were: 18.4% vs 21.0%, 23.9% vs 32.3% and 4.0% vs 6.5%, respectively; mortality rates were 20.8% vs 22.65%; mechanical ventilation durations were 18.30 d vs 17.56 d while lengths of stay in the intensive care units (ICU) were 19.87 d vs 19.19 ± 5.19 d. Differences in the above factors between groups were not significant. Gastric residual ≥ 250 mL was not an independent risk factor for death and prolonged ICU stay. However, target feeding time of patients in the ≥ 250 mL group was longer than that of patients in the ≥ 250 mL group, and caloric intake (22.0, 23.6, 24.8, 25.3 kcal/kg/d) for patients in the ≥ 250 mL group from the 4th day to the 7th day of hospitalization was lower than that of patients in the ≥ 250 mL group (23.2, 24.8, 25.7, 25.8 kcal/kg/d). On the 4th day (Z = 4.324, P = 0.013), on the 5th day (Z = 3.376, P = 0.033), while on the 6th day (Z = 3.098, P = 0.04), the differences were statistically significant. CONCLUSION: The use of ultrasound to monitor GRV and undertaking clinical interventions when the monitoring value is ≥ 250 mL has no significant effects on incidences of feeding complications and clinical prognostic outcomes, however, it significantly prolongs the time to reach target feeding, reduces the daily intake of calories during ICU hospitalization, and increases the risk of insufficient nutrition of patients. The accuracy and necessity of monitoring gastric remnants and monitoring frequencies should be investigated further.

Multiple heart-cutting two-dimensional liquid chromatography/charged aerosol detector assay of ginsenosides for quality evaluation of ginseng from diverse Chinese patent medicines.

For quality control of Chinese patent medicines (CPMs) containing the same herbal medicine or different herbal medicines that have similar chemical composition, current ″one standard for one species″ research mode leads to poor universality of the analytical approaches unfavorable to discriminate easily confused species. Herein, we were aimed to elaborate a multiple heart-cutting two-dimensional liquid chromatography/charged aerosol detector (MHC-2DLC/CAD) approach to quantitatively assess ginseng from multiple CPMs. Targeting baseline resolution of 16 ginsenosides (noto-R1/Rg1/Re/Rf/Ra2/Rb1/Rc/Ro/Rb2/Rb3/Rd/Rh1/Rg2/Rg3/Rg3(R)/24(R)-p-F11), experiments were conducted to optimize key parameters and validate its performance. A Poroshell 120 EC-C18 column and an XBridge Shield RP18 column were separately utilized in the first-dimensional (1D) and the second-dimensional (2D) chromatography. Eight consecutive cuttings could achieve good separation of 16 ginsenosides within 85 min. The developed MHC-2DLC/CAD method showed good linearity (R2 > 0.999), repeatability (RSD < 6.73%), stability (RSD < 5.63%), inter- and intra-day precision (RSD < 5.57%), recovery (93.76-111.14%), and the limit of detection (LOD) and limit of quantification (LOQ) varied between 0.45-2.37 ng and 0.96-4.71 ng, respectively. We applied it to the content determination of 16 ginsenosides simultaneously from 28 different ginseng-containing CPMs, which unveiled the ginsenoside content difference among the tested CPMs, and gave useful information to discriminate ginseng in the preparation samples, as well. The MHC-2DLC/CAD approach exhibited advantages of high specificity, good separation ability, and relative high analysis efficiency, which also justified the feasibility of our proposed ″Monomethod Characterization of Structure Analogs″ strategy in quality evaluation of diverse CPMs that contained different ginseng.

Use of tumor suppressor genes of naked mole rats for human cancer treatment.

Cancer not only has a significant prevalence in the human population, but is also leading cause of death in animals. Despite a long history, our battle against cancer continues. Cross-species comparative genomics offers insight into shared genes and pathways by analyzing genomic data across species, enhancing our understanding of cancer mechanisms, evolutionary processes, and possible therapeutic targets. However, no previous study has demonstrated the inhibitory effects of tumor suppressor genes from one species on tumor cells from another. The naked mole rat is the only mammal yet to be found with cancer that is attributed to its tumor suppressor genes. In this study, we constructed phylogenetic trees and assessed the anti-tumor activity of two suppressor genes, programmed cell death molecule 5 (PDCD5) and dickkopf 3 (DKK3), from rats, mice, and humans. DKK3 robustly inhibited the proliferation of breast cancer cells within and across species due to its highly conserved protein sequence. However, the cross-species inhibitory effect of PDCD5 on breast cancer cells was inconsistent due to significant sequence variations. Intriguingly, PDCD5 from the naked mole rat demonstrated potent anti-tumor activity against breast cancer cells from mice, rats, and humans, surpassing that of PDCD5 from parental species. Our results demonstrate that the suppressor genes from the naked mole rat have a strong inhibitory effect on cancer cells, indicating that the powerful anti-cancer functions of the naked mole rat may be useful for human tumor treatment.

Characterization and comparison of cardiomyocyte protection activities of non-starch polysaccharides from six ginseng root herbal medicines.

Ginseng is rich of polysaccharides, however, the evidence supporting polysaccharides to distinguish various ginseng species is rarely reported. Focusing on six root ginseng (e.g., Panax ginseng-PG, P. quinquefolius-PQ, P. notoginseng-PN, red ginseng-RG, P. japonicus-PJ, and P. japonicus var. major-PJM), the contained non-starch polysaccharides (NPs) were structurally characterized and compared by both the chemical and biological evaluation. Holistic fingerprinting at three levels (the NPs and the acid hydrolysates involving oligosaccharides and monosaccharides) utilized various chromatography methods, and the treatment of H9c2 cells with the NPs by OGD and H2O2-induced injury models was used to assess the protective effect. NPs from six Panax herbal medicines occupied about 20 % of the total polysaccharides, which were of the highest content in RG and the lowest in PN. NPs from six ginseng exhibited weak differentiations in the molecular weight distribution, while marker oligosaccharides were found to distinguish PN and RG from the others. Glc and GalA were more abundant in the NPs for PG and RG, respectively. NPs from PQ (100/200 µg/mL) showed significant cardiomyocyte protection effect by regulating the mitochondrial functions. This work further testifies the role of polysaccharides in quality control of herbal medicine, with new markers discovered beneficial to distinguish the ginseng.

Individual with concurrent chest wall tuberculosis and triple-negative essential thrombocythemia: A case report.

BACKGROUND: Chest wall tuberculosis (TB) and triple-negative essential thrombocythemia (TN-ET) are rare medical conditions, and their combination is extremely rare globally. Only one case of TB peritonitis with thrombocytosis has been reported, which was identified in 1974. CASE SUMMARY: Herein, we report the case of a 23-year-old man with concurrent chest wall mass and TN-ET. The patient presented to a local hospital due to having a headache and low-grade fever for 2 d, with their bodily temperature fluctuating at around 36.8 °C. Hematological analysis showed a high platelet count of 1503 × 109/L. Subsequently, the patient visited our hospital for further investigation. Computed tomography of the chest suggested a submural soft tissue density shadow in the left lower chest wall. After surgical resection, the pathological findings of the swelling were reported as TB with massive caseous necrosis. According to the World Health Organization diagnostic criteria, the patient was diagnosed with TN-ET, as they met the requirement of four main criteria or the first three main criteria and one secondary criterion. The patient was eventually diagnosed with chest wall TB with TN-ET, which is extremely rare. CONCLUSION: Chest wall TB is rare. TN-ET diagnosis requires secondary factor exclusion and satisfaction of primary diagnostic criteria. miRNA, combined with the methylation process, could explain suppressor of cytokine signaling (SOCS) 1 and SOCS3 downregulation in ET-JAK2V617F-negative patients. The miRNA could participate in JAK2 pathway activation. SOCS3 may be a novel MPN biomarker.

Anterolateral thigh flow-through flap: A versatile method for reconstruction of complex extremity defects.

BACKGROUND: Flow-through flaps have been widely applied only for the reconstruction of complex defects in the extremities because they can be used for arterial reconstruction and soft tissue coverage simultaneously. This report attempts to fully demonstrate the role of the anterolateral thigh (ALT) flow-through flap as a versatile method for reconstructing complex defects in the extremities. METHODS: From February 2011 to March 2017, we retrospectively analyzed the use of a reconstructive surgical technique based on the ALT flow-through flap to treat complex extremity defects in 87 patients (trauma, n = 79; diabetic ulcers, n = 5; squamous cell carcinoma, n = 3). Emergency surgery was performed in 12 patients to bridge a major artery gap and was followed by elective reconstruction in the remaining patients. Applications of the ALT flow-through flap included bridging major artery gaps, preserving recipient blood vessel integrity, reconstructing blood vessel continuity, protecting vascular anastomoses, avoiding difficult end-to-side anastomoses in the recipient area, and balancing blood flow, as well as combined application with an additional flap. RESULTS: The flap size ranged from 6 × 3 cm to 17 × 9 cm. ALT flow-through flaps were used in combination with an additional flap (n = 4) and in vascular reconstruction (n = 83). Three patients required of the microvascular anastomostic reexploration for venous congestion, total necrosis occurred in two patients, and partial necrosis occurred in one patient. At the donor site, there were three cases of infection and two cases of wound dehiscence. At the recipient site, one case of infection and two cases of wound dehiscence were observed. One patient presented with deep infection secondary to renal failure and underwent amputation. During the follow-up period (range, 1-33 months), all other flaps (84 cases) survived uneventfully, with normal texture and color. CONCLUSION: The ALT flow-through flap plays many roles as it is a versatile method for reconstructing complex defects of the extremities and serves various other clinical purposes.

Impact of extended nursing model after multi-disciplinary treatment on young patient with post-stroke.

BACKGROUND: Stroke has become one of the most serious life-threatening diseases due to its high morbidity, disability, recurrence and mortality rates. AIM: To explore the intervention effect of multi-disciplinary treatment (MDT) extended nursing model on negative emotions and quality of life of young patients with post-stroke. METHODS: A total of 60 young stroke patients who were hospitalized in the neurology department of our hospital from January 2020 to December 2021 were selected and randomly divided into a control group and an experimental group, with 30 patients in each group. The control group used the conventional care model and the experimental group used the MDT extended nursing model. After the in-hospital and 3-mo post-discharge interventions, the differences in negative emotions and quality of life scores between the two groups were evaluated and analyzed at the time of admission, at the time of discharge and after discharge, respectively. RESULTS: There are no statistically significant differences in the negative emotions scores between the two groups at admission, while there are statistically significant differences in the negative emotions scores within each group at admission and discharge, at discharge and post-discharge, and at discharge and post-discharge. In addition, the negative emotions scores were all statistically significant at discharge and after discharge when compared between the two groups. There was no statistically significant difference in quality of life scores at the time of admission between the two groups, and the difference between quality of life scores at the time of admission and discharge, at the time of discharge and post-discharge, and at the time of admission and post-discharge for each group of patients was statistically significant. CONCLUSION: The MDT extended nursing mode can improve the negative emotion of patients and improve their quality of life. Therefore, it can be applied in future clinical practice and is worthy of promotion.

[Content determination of ten flavonoids and alkaloids in Gleditsiae Sinensis Fructus, Gleditsiae Fructus Abnormalis, and Gleditsiae Spina].

To study the quality control of three traditional Chinese medicines derived from Gleditsia sinensis [Gleditsiae Sinensis Fructus(GSF), Gleditsiae Fructus Abnormalis(GFA), and Gleditsiae Spina(GS)], this paper established a multiple reaction monitoring(MRM) approach based on ultra-high performance liquid chromatography-triple quadrupole-linear ion-trap mass spectrometry(UHPLC-Q-Trap-MS). Using an ACQUITY UPLC BEH C_(18) column(2.1 mm × 100 mm, 1.7 µm), gradient elution was performed at 40 ℃ with water containing 0.1% formic acid-acetonitrile as the mobile phase running at 0.3 mL·min~(-1), and the separation and content determination of ten chemical constituents(e.g., saikachinoside A, locustoside A, orientin, taxifolin, vitexin, isoquercitrin, luteolin, quercitrin, quercetin, and apigenin) in GSF, GFA, and GS were enabled within 31 min. The established method could quickly and efficiently determine the content of ten chemical constituents in GSF, GFA, and GS. All constituents showed good linearity(r>0.995), and the average recovery rate was 94.09%-110.9%. The results showed that, the content of two alkaloids in GSF(2.03-834.75 µg·g~(-1)) was higher than that in GFA(0.03-10.41 µg·g~(-1)) and GS(0.04-13.66 µg·g~(-1)), while the content of eight flavonoids in GS(0.54-2.38 mg·g~(-1)) was higher than that in GSF(0.08-0.29 mg·g~(-1)) and GFA(0.15-0.32 mg·g~(-1)). These results provide references for the quality control of G. sinensis-derived TCMs.

Comparative Characterization of the Ginsenosides from Six Panax Herbal Extracts and Their In Vitro Rat Gut Microbial Metabolites by Advanced Liquid Chromatography-Mass Spectrometry Approaches.

Ginseng extracts are extensively used as raw materials for food supplements and herbal medicines. This study aimed to characterize ginsenosides obtained from six Panax plant extracts (Panax ginseng, red ginseng, Panax quinquefolius, Panax notoginseng, Panax japonicus, and Panax japonicus var. major) and compared them with their in vitro metabolic profiles mediated by rat intestinal microbiota. Ultrahigh-performance liquid chromatography/ion mobility-quadrupole time-of-flight mass spectrometry (UHPLC/IM-QTOF-MS) with scheduled multiple reaction monitoring (sMRM) quantitation methods were developed to characterize and compare the ginsenoside composition of the different extracts. After in vitro incubation, 248 ginsenosides/metabolites were identified by UHPLC/IM-QTOF-MS in six biotransformed samples. Deglycosylation was determined to be the main metabolic pathway of ginsenosides, and protopanaxadiol-type and oleanolic acid-type saponins were easier to be easily metabolized. Compared with the ginsenosides in plant extracts, those remaining in six biotransformed samples were considerably fewer after biotransformation for 8 h. However, the compositional differences in four subtypes of the ginsenosides among the six Panax plants became more distinct.

Imbalance of multiple neurotransmitter pathways leading to depression-like behavior and cognitive dysfunction in the triple transgenic mouse model of Alzheimer disease.

Depression is among the most frequent psychiatric comorbid conditions in Alzheimer disease (AD). However, pharmacotherapy for depressive disorders in AD is still a big challenge, and the data on the efffcacy of current antidepressants used clinically for depressive symptoms in patients with AD remain inconclusive. Here we investigated the mechanism of the interactions between depression and AD, which we believe would aid in the development of pharmacological therapeutics for the comorbidity of depression and AD. Female APP/PS1/Tau triple transgenic (3×Tg-AD) mice at 24 months of age and age- and sex-matched wild-type (WT) mice were used. The shuttle-box passive avoidance test (PAT) were implemented to assess the abilities of learning and memory, and the open field test (OFT) and the tail suspension test (TST) were used to assess depression-like behavior. High-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) was used to detect the level of neurotransmitters related to depression in the hippocampus of mice. The data was identified by orthogonal projections to latent structures discriminant analysis (OPLS-DA). Most neurotransmitters exert their effects by binding to the corresponding receptor, so the expression of relative receptors in the hippocampus of mice was detected using Western blot. Compared to WT mice, 3×Tg-AD mice displayed significant cognitive impairment in the PAT and depression-like behavior in the OFT and TST. They also showed significant decreases in the levels of L-tyrosine, norepinephrine, vanillylmandelic acid, 5-hydroxytryptamine, and acetylcholine, in contrast to significant increases in 5-hydroxyindoleacetic acid, L-histidine, L-glutamine, and L-arginine in the hippocampus. Moreover, the expression of the alpha 1a adrenergic receptor (ADRA1A), serotonin 1 A receptor (5HT1A), and γ-aminobutyric acid A receptor subunit alpha-2 (GABRA2) was significantly downregulated in the hippocampus of 3×Tg-AD mice, while histamine H3 receptor (H3R) expression was significantly upregulated. In addition, the ratio of phosphorylated cAMP-response element-binding protein (pCREB) and CREB was significantly decreased in the hippocampus of 3×Tg-AD mice than WT mice. We demonstrated in the present study that aged female 3×Tg-AD mice showed depression-like behavior accompanied with cognitive dysfunction. The complex and diverse mechanism appears not only relevant to the imbalance of multiple neurotransmitter pathways, including the transmitters and receptors of the monoaminergic, GABAergic, histaminergic, and cholinergic systems, but also related to the changes in L-arginine and CREB signaling molecules.

miR-130a targets CiGadd45bb to modulate the inflammatory response to bacterial infection in Ctenopharyngodon idella kidney (CIK) cells.

Septicemia is a systemic inflammatory response to bacterial infection that results in a hyper-inflammatory state, which could lead to septic shock and death in grass carp (Ctenopharyngodon idella). The aim of this study was to determine the underlying mechanism of microRNA (miR-130a) in bacteria-infected grass carp. Expression levels of miR-130a against Aeromonas hydrophila (A. hydrophila) infection in Ctenopharyngodon idella kidney cells (CIK) were analyzed. Luciferase reporter assay, quantitative reverse transcription-polymerase chain reaction were performed to explore whether Ctenopharyngodon idella growth arrest and DNA damage-inducible 45 (CiGadd45bb) was a target of miR-130a. MiR-130a mimic, inhibitor and miR-control were transfected to CIK respectively. After transfection, the expression levels of proinflammatory genes were determined. Here we show that CiGadd45bb as a target of miR-130a. We also confirmed that miR-130a levels were significantly higher after being stimulated for 4 h and lower after 12 h (P < 0.01). Overexpressing miR-130a strikingly inhibited p38, JNK, ERK and TNF-a genes (P < 0.01) and silencing miR-130a activated p38, JNK, ERK, TNF-a, IFN and IL-8 (P < 0.01). Our results provide a theoretical basis for studying the molecular mechanism underlying the regulation of inflammation by miR-130a in grass carp.

[Standardized Jin's three-needle therapy for stroke: a randomized controlled trial].

OBJECTIVE: To observe the effect of standardized Jin's three-needle therapy on limb motor function and nerve function defect in stroke patients, and to evaluate the placebo control method. METHODS: A total of 66 patients with stroke were randomly divided into a Jin's three-needle group (33 cases, 3 cases dropped off) and a placebo needle group (33 cases, 4 cases dropped off). All the patients were treated with conventional medication and rehabilitation treatment. In addition, the patients in the Jin's three-needle group were treated with standardized Jin's three-needle therapy at temporal three points, spirit four points, hand three points, foot three points, upper extremity spasm three points, lower extremity spasm three points, etc.; while the patients in the placebo needle group were treated with placebo needling at identical points. All the treatments were given once a day, 5 days a week, and 3-week treatment was given with an interval of 2 days between weeks. The scores of Fugl-Meyer assessment scale (FMA) and National Institutes of Health stroke scale (NIHSS) were observed before treatment, 10 d and 21 d into treatment, and the blind evaluation was conducted after treatment. RESULTS: On the 10 d and 21 d into treatment, the FMA scores in both groups were higher than those before treatment (P<0.01), and the NIHSS scores were lower than those before treatment (P<0.01). On the 10 d and 21 d into treatment, the FMA scores in the Jin's three-needle group were higher than those in the placebo needle group (P<0.05); on the 10 d into treatment, the NIHSS score in the Jin's three-needle group was were lower than that in the placebo needle group (P<0.05). There was no significant difference between the two groups on judging the type of treatment (P>0.05), and the consistency with the real situation was poor (Cohen's kappa coefficient<0.20). CONCLUSION: The standardized Jin's three-needle therapy could effectively improve the limb motor function and nerve function defect in stroke patients. The placebo control method used in this study shows good clinical operability and masking effect.

Metabolism in Cancer Stem Cells: Targets for Clinical Treatment.

Cancer stem cells (CSCs) have high tumorigenicity, high metastasis and high resistance to treatment. They are the key factors for the growth, metastasis and drug resistance of malignant tumors, and are also the important reason for the occurrence and recurrence of tumors. Metabolic reprogramming refers to the metabolic changes that occur when tumor cells provide sufficient energy and nutrients for themselves. Metabolic reprogramming plays an important role in regulating the growth and activity of cancer cells and cancer stem cells. In addition, the immune cells or stromal cells in the tumor microenvironment (TME) will change due to the metabolic reprogramming of cancer cells. Summarizing the characteristics and molecular mechanisms of metabolic reprogramming of cancer stem cells will provide new ideas for the comprehensive treatment of malignant tumors. In this review, we summarized the changes of the main metabolic pathways in cancer cells and cancer stem cells.

A multi-dimensional liquid chromatography/high-resolution mass spectrometry approach combined with computational data processing for the comprehensive characterization of the multicomponents from Cuscuta chinensis.

Challenges encountered in plant metabolites characterization by liquid chromatography/mass spectrometry can arise from the insufficient chromatography separation, the lack of specific database, and low reliability of identification because of the ubiquitous isomerism. Herein, we present an integral approach, by combining comprehensive off-line two-dimensional liquid chromatography/ion mobility-quadrupole time-of-flight mass spectrometry (2D-LC/IM-QTOF-MS), automatic peak annotation, molecular networking, and collision cross section (CCS) prediction, aimed to improve the resolution and reliability in MS-oriented metabolites characterization. Using the seeds of Cuscuta chinensis as a case, the configuration of an XBridge Amide column of hydrophilic interaction chromatography (HILIC) and a Zorbax SB-Aq column of reversed-phase chromatography (RPC), in an off-line mode, showed the orthogonality of 0.73 and effective peak capacity of 4361. Data-independent high-definition MSE (HDMSE) in the negative mode could enable high-coverage MS2 data acquisition and enhance the ions resolution, while computational peak annotation workflows facilitated by UNIFITM and Global Natural Products Social Molecular Network (GNPS) could efficiently characterize the targeted and untargeted compound analogs. A total of 302 compounds were identified or tentatively characterized, and 109 thereof were unreported. Moreover, CCS prediction (www.allccs.zhulab.cn) provided more possibilities to distinguish 12 pairs of isomers in the lack of reference standards. The 2D-LC/IM-QTOF-MS approach enabled the collection of five dimension of data related to each component (tR by HILIC and RPC, CCS, m/z in MS1 and MS2), and the intelligent metabolites characterization with more reliable MS data. Conclusively, the established integral strategy can be utilized in metabolome analysis to support the quality control of herbal medicines.

A Novel Pyroptosis-Related Prognostic Signature for Risk Stratification and Clinical Prognosis in Clear Cell Renal Cell Carcinoma.

Emerging research has substantiated that pyroptosis-related biomarkers were mightily related to the clinical outcome of patients with clear cell renal cell carcinoma (ccRCC). However, a single-gene biomarker's moderate predictive power is insufficient, and more accurate prognostic models are urgently needed. We conducted this investigation in order to develop a robust pyroptosis-related gene signature for use in risk stratification and survival prognosis in colorectal cancer. We downloaded transcriptomic data and survival information of ccRCC patients from TCGA. Bioinformatic methods were used to generate a pyroptosis-related gene signature based on data from TCGA training cohort. ROC curve, uni- and multivariate regression analyses were used for the prognostic assays. What is more, we explored the relationship between model-based risk score and the tumor microenvironment. Herein, 11 pyroptosis-related hub genes (CASP9, TUBB6, NFKB1, BNIP3, CAPN1, CD14, PRDM1, BST2, SDHB, TFAM, and GSDMB) were determined as risk signature for risk stratification and prognosis prediction for ccRCC. Kaplan-Meier curves, ROC curves, and risk plots were employed to analyze and verify its performance in all groups. Multivariate assays exhibited that risk score could be an independent prognostic factor for patients' OS. ESTIMATE algorithm showed a higher immune score in the group of high-risk. Overall, a novel pyroptosis-related gene signature generated can be employed for prognosis prediction of ccRCC patients. This may assist in individual treatment of clinical decision-making.

Efficacy of intravitreal conbercept injection on short- and long-term macular edema in branch retinal vein occlusion.

AIM: To observe the best-corrected visual acuity (BCVA) and central foveal thickness (CFT) repeatedly after the intravitreal injection of conbercept (IVC) for treating cystoid macular edema (CME) in branch retinal vein occlusion (BRVO) and explore the relationship between the duration of CME and visual outcome. METHODS: Subgroup analysis was performed to compare short-term (within 90d of CME onset) and long-term (over 90d of CME onset) macular edema in BRVO. After an initial IVC, a pro re nata (PRN) strategy was performed according to the recurrence of CFT or decrease of BCVA. Analysis of variance using repeated measurements, statistical analysis following indicators including BCVA and CFT collected at baseline and 1, 3, and 6mo after IVC. RESULTS: Among the 60 cases included in this retrospective study, 36 were short-term CME, and 24 were long-term CME. There were statistical significances between and within groups of the BCVAs at different time points (P<0.001). The interaction was found between group and time (P=0.006), indicating the difference in the speed of BCVA improvement between groups. In particular, the improvement speed of BCVA in the short-term CME group was faster than that in the long-term CME group. There were significant differences between and with groups of the CFT at different time points (P<0.001). However, the interaction between group and time in relation to CFT had no significant differences (P=0.59). CONCLUSION: IVC treatment for CME following BRVO is effective and safe. The duration of CME before treatment is a significant predictor of the visual outcomes of patients with BRVO. The improvement of vision might be faster with early IVC treatment than with delayed treatment.