Characterization of SgALMT genes reveals the function of SgALMT2 in conferring aluminum tolerance in Stylosanthes guianensis through the mediation of malate exudation.

Aluminum (Al) toxicity is the major constraint on plant growth and productivity in acidic soils. An adaptive mechanism to enhance Al tolerance in plants is mediated malate exudation from roots through the involvement of ALMT (Al-activated malate transporter) channels. The underlying Al tolerance mechanisms of stylo (Stylosanthes guianensis), an important tropical legume that exhibits superior Al tolerance, remain largely unknown, and knowledge of the potential contribution of ALMT genes to Al detoxification in stylo is limited. In this study, stylo root growth was inhibited by Al toxicity, accompanied by increases in malate and citrate exudation from roots. A total of 11 ALMT genes were subsequently identified in the stylo genome and named SgALMT1 to SgALMT11. Diverse responses to metal stresses were observed for these SgALMT genes in stylo roots. Among them, the expressions of 6 out of the 11 SgALMTs were upregulated by Al toxicity. SgALMT2, a root-specific and Al-activated gene, was selected for functional characterization. Subcellular localization analysis revealed that the SgALMT2 protein is localized to the plasma membrane. The function of SgALMT2 in mediating malate release was confirmed by analysis of the malate exudation rate from transgenic composite stylo plants overexpressing SgALMT2. Furthermore, overexpression of SgALMT2 led to increased root growth in transgenic stylo plants treated with Al through decreased Al accumulation in roots. Taken together, the results of this study suggest that malate secretion mediated by SgALMT2 contributes to the ability of stylo to cope with Al toxicity.

Safety of Ustekinumab in Inflammatory Bowel Disease: Pooled Safety Analysis Through 5 Years in Crohn's Disease and 4 Years in Ulcerative Colitis.

BACKGROUND AND AIMS: Previously published long-term safety data reported a favorable ustekinumab safety treatment profile for treatment of inflammatory bowel disease (IBD). We present the final cumulative safety data from pooled ustekinumab IBD phase 2/3 clinical studies through 5 years in Crohn's disease (CD) and 4 years in ulcerative colitis (UC). METHODS: In phase 3 studies, patients received a single IV placebo or ustekinumab (130mg or ~6mg/kg) induction dose followed by subcutaneous maintenance doses of placebo or ustekinumab (90mg q8w or q12w). Analyses included all patients who received one dose of study treatment and included patients who were biologic-naïve and patients with a history of biologic failure. Safety outcomes are summarized and presented using number of events per 100 patient-years of follow-up and corresponding 95% confidence interval. RESULTS: In this final pooled safety analysis, 2575 patients were treated with ustekinumab with 4826 patient-years of follow-up. Rates of key safety events, including MACE and malignancies, were similar between placebo and ustekinumab or not higher for ustekinumab.Opportunistic infections, including tuberculosis, and malignancies were reported infrequently. Rates of key safety events in the IBD group were no higher in the ustekinumab group than in the placebo group for both patients who were biologic naïve or who had previously failed a biologic. No lymphomas or cases of posterior reversible encephalopathy syndrome (PRES; formerly known as reversible posterior leukoencephalopathy syndrome [RPLS] were reported. CONCLUSION: The final cumulative ustekinumab safety data through 5 years in CD and 4 years in UC demonstrated favorable safety compared to placebo and continues to support the well-established safety profile across all approved indications.

Efficacy and Safety of Ustekinumab for Ulcerative Colitis Through 4 Years: Final Results of the UNIFI Long-Term Maintenance Study.

INTRODUCTION: Ulcerative colitis (UC) is a chronic condition that may require long-term treatment. We report the final efficacy and safety results of the UNIFI long-term extension study of ustekinumab in patients with UC through 4 years. METHODS: Ustekinumab induction responders who completed 44 weeks of maintenance treatment and agreed to enter the long-term extension continued their subcutaneous maintenance therapy (90 mg ustekinumab every 8 or 12 weeks [q8w or q12w] or placebo). Starting at week 56, randomized patients could receive dose adjustment to 90 mg q8w. Symptoms and adverse events were assessed through the study; endoscopic assessment was conducted at week 200. RESULTS: Of the 348 patients randomized to subcutaneous ustekinumab at maintenance baseline (q8w and q12w combined), 55.2% were in symptomatic remission at week 200. A greater proportion of biologic-naive patients (67.2% [117/174]) were in symptomatic remission than those with a history of biologic failure (41.6% [67/161]). Among patients in symptomatic remission at week 200, 96.4% were corticosteroid-free. Of the 171 patients with endoscopic evaluation at week 200, 81.6% (71/87) in the q12w group and 79.8% (67/84) in the q8w group had endoscopic improvement. From weeks 156 to the final safety visit (up to week 220), no deaths, major adverse cardiovascular events, or tuberculosis occurred in patients receiving ustekinumab. Nasopharyngitis, UC worsening, and upper respiratory tract infections were the most frequently reported adverse events. DISCUSSION: The long-term efficacy of ustekinumab maintenance in patients with UC was confirmed through 4 years. No new safety signals were observed. ClinicalTrials.gov number NCT02407236.

Development of transgenic composite Stylosanthes plants to study root growth regulated by a ß-expansin gene, SgEXPB1, under phosphorus deficiency.

KEY MESSAGE: A highly efficient transformation procedure to generate transgenic Stylosanthes roots was established. SgEXPB1 is involved in Stylosanthes root growth under phosphorus deficiency. Stylo (Stylosanthes spp.) is an important forage legume widely applied in agricultural systems in the tropics. Due to the recalcitrance of stylo genetic transformation, functional characterization of candidate genes involved in stylo root growth is limited. This study established an efficient procedure for Agrobacterium rhizogenes-mediated transformation for generating transgenic composite plants of S. guianensis cultivar 'Reyan No. 5'. Results showed that composite stylo plants with transgenic hairy roots were efficiently generated by A. rhizogenes strains K599 and Arqual, infecting the residual hypocotyl at 1.0 cm of length below the cotyledon leaves of 9-d-old seedlings, leading to a high transformation efficiency of > 95% based on histochemical ß-glucuronidase (GUS) staining. Notably, 100% of GUS staining-positive hairy roots can be achieved per composite stylo plant. Subsequently, SgEXPB1, a ß-expansin gene up-regulated by phosphorus (P) deficiency in stylo roots, was successfully overexpressed in hairy roots. Analysis of hairy roots showed that root growth and P concentration in the transgenic composite plants were increased by SgEXPB1 overexpression under low-P treatment. Taken together, a highly efficient A. rhizogenes-mediated transformation procedure for generating composite stylo plants was established to study the function of SgEXPB1, revealing that this gene is involved in stylo root growth during P deficiency.

Comprehensive Characterization of RNA-Binding Proteins in Colon Adenocarcinoma Identifies a Novel Prognostic Signature for Predicting Clinical Outcomes and Immunotherapy Responses Based on Machine Learning.

BACKGROUND: RNA-binding proteins (RBPs) are crucial factors that function in the posttranscriptional modification process and are significant in cancer. OBJECTIVE: This research aimed for a multigene signature to predict the prognosis and immunotherapy response of patients with colon adenocarcinoma (COAD) based on the expression profile of RNA-binding proteins (RBPs). METHODS: COAD samples retrieved from the TCGA and GEO datasets were utilized for a training dataset and a validation dataset. Totally, 14 shared RBP genes with prognostic significance were identified. Non-negative matrix factorization clusters defined by these RBPs could stratify COAD patients into two molecular subtypes. Cox regression analysis and identification of 8-gene signature categorized COAD patients into high- and low-risk populations with significantly different prognosis and immunotherapy responses. RESULTS: Our prediction signature was superior to another five well-established prediction models. A nomogram was generated to quantificationally predict the overall survival (OS) rate, validated by calibration curves. Our findings also indicated that high-risk populations possessed an enhanced immune evasion capacity and low-risk populations might benefit immunotherapy, especially for the joint combination of PD-1 and CTLA4 immunosuppressants. DHX15 and LARS2 were detected with significantly different expressions in both datasets, which were further confirmed by qRTPCR and immunohistochemical staining. CONCLUSION: Our observations supported an eight-RBP-related signature that could be applied for survival prediction and immunotherapy response of patients with COAD.

Effect of standardized training of rehabilitation therapists in Beijing based on rehabilitation competency framework / 中国康复理论与实践

ObjectiveTo analyze the effect of standardized training on post competency of rehabilitation therapists, based on World Health Organization rehabilitation competency framework (RCF), and combined with the characteristics of rehabilitation and the requirements of standardized training in China. MethodsFrom 2018 to 2022, a total of 30 rehabilitation therapists who participated in the standardized training were selected. Before and after the standardized training, the closed-book theoretical assessment and Mini-clinical Evaluation Exercise (Mini-CEX) assessment were carried out, and a 360-Degree Evaluation scale was distributed to their teachers, peers and patients. Through multi-dimensional post competency analysis, the data obtained from the scales were combined with the five dimensions of basic theoretical knowledge, clinical practice ability, medical humanities literacy, scientific research and teaching ability, and organizational management ability to analyze the effect of standardized training on post competency of rehabilitation therapists. ResultsAfter training, the therapists improved in theory and case analysis (Z > 2.716, P < 0.05). They also improved in medical interview skills, physical examination, humane care/professionalism, clinical judgment ability and overall clinical level (Z > 2.162, P < 0.05) according to Mini-CEX. The medical ethics, daily work, management ability, social ability, interpersonal communication ability, basic professional ability and operation ability improved (Z > 1.978, P < 0.05) according to the 360-Degree Evaluation scale. The effect of standardized training was significant in basic theoretical knowledge, clinical practice ability and medical humanities literacy by the post competency analysis model. ConclusionThe effect of standardized training of rehabilitation therapists is significant, and the therapists can be competent for daily work in diagnosis and treatment after training.

Characterastics of muscle architectural parameters for early knee osteoarthritis in middle-aged and elderly women / 中国康复理论与实践

ObjectiveTo observe the architectural parameter changes of the muscles around the knee in middle-aged and elderly women with early knee osteoarthritis (KOA) by musculoskeletal ultrasound, and to clarify the indicators of muscles that affect early KOA. MethodsFrom January to August, 2022, 20 healthy middle-aged and elderly healthy women (controls) and 20 middle-aged and elderly women with unilateral early KOA (KOA group) were recruited through Beijing Bo'ai Hospital, to measure muscle thickness of the popliteus muscle, the muscle thickness and the pennation angle of the quadriceps, as rectus femoris, vastus intermedius, vastus lateralis, vastus medialis longus and vastus medialis oblique. ResultsCompared with the healthy limb of KOA group, and the controls, the muscle thickness of vastus medialis longus, vastus medialis oblique and popliteus muscle of the affected limb of KOA group became thinner (t > 2.133, P < 0.05); the proportion of thickness of vastus medialis oblique to thickness of vastus lateralis became smaller (t > 3.660, P < 0.05). The pennation angle was smaller in the affected limb of KOA group than in the matched dominant side of the controls (t = 3.101, P < 0.05). Logistic regression analysis showed that the muscle thickness of vastus medialis oblique (OR = 0.235, 95%CI 0.068 to 0.805, P = 0.021) and popliteus muscle (OR = 0.387, 95%CI 0.152 to 0.980, P = 0.045) were related to the onset of early KOA. ConclusionThe thickness of vastus medialis longus, vastus medialis oblique and popliteus muscle decrease, and the balance of the strength of vastus medialis oblique and vastus lateralis weakens in the affected limbs of the middle-aged and elderly women with early KOA. The thickness of vastus medialis oblique and popliteus muscle are protective factors for onset of KOA.

Isolation and quantification of a 17-epi-dammarane triterpenoid rhuslactone from roots of Rhus chinensis and its preventive effects on coronary heart disease and thrombosis in zebrafish / 中国中药杂志

Based on mass spectrometry(MS)-guided separation strategy, compound 1 was obtained from the roots of Rhus chinensis. By comprehensive analysis of high resolution-electrospray ionization-mass spectrometry(HR-ESI-MS), nuclear magnetic resonance(NMR) data, and quantum chemical calculation of NMR(qcc-NMR) parameters, compound 1 was elucidated as rhuslactone, a 17-epi-dammarane triterpenoid with a rare 17α-side chain. An HPLC-ELSD method for its quantification in R. chinensis was established and adopted for the quantification of rhuslactone in different batches of R. chinensis. Rhuslactone displayed a good linear relationship within the range of 0.021 3-1.07 μmol·mL~(-1 )(r=0.997 6), and the average recovery was 99.34% [relative standard deviation(RSD) 2.9%). Moreover, the results of the evaluation test of the preventive effects of rhusalctone on coronary heart disease(CHD) and thrombosis showed that rhuslactone(0.11 nmol·mL~(-1)) significantly alleviated heart enlargement and venous congestion and increased cardiac output(CO), blood flow velocity(BFV), and heart rate, thereby reducing thrombus formation in zebrafish with CHD. The effects of rhuslactone on CO and BFV were superior to that of digoxin(1.02 nmol·mL~(-1)), and its effect on improving heart rate was comparable to that of digoxin. This study provides experimental references for the isolation, identification, quality control, and application of rhuslactone from R. chinensis against CHD. It is worth mentioning that this study has discussed some omissions in the determination of the stereochemistry of C-17 in dammarane triterpenoids in the present coursebook Chemistry of Chinese Medicine and some research papers, that is, the compound may be 17-epi-dammarane triterpenoid. This paper has also proposed steps for the establishment of C-17 stereochemistry.

SgNramp1, a plasma membrane-localized transporter, involves in manganese uptake in Stylosanthes guianensis.

Transporters belonging to the natural resistance-associated macrophage protein (Nramp) family play important roles in metal uptake and homeostasis. Although Nramp members have been functionally characterized in plants, the role of Nramp in the important tropical forage legume Stylosanthes guianensis (stylo) is largely unknown. This study aimed to determine the responses of Nramp genes to metal stresses and investigate its metal transport activity in stylo. Five SgNramp genes were identified from stylo. Expression analysis showed that SgNramp genes exhibited tissue preferential expressions and diverse responses to metal stresses, especially for manganese (Mn), suggesting the involvement of SgNramps in the response of stylo to metal stresses. Of the five SgNramps, SgNramp1 displayed the highest expression in stylo roots. A close correlation between SgNramp1 expression and root Mn concentration was observed among nine stylo cultivars under Mn limited condition. The higher expression of SgNramp1 was correlated with a high Mn uptake in stylo. Subsequent subcellular localization analysis showed that SgNramp1 was localized to the plasma membrane. Furthermore, heterologous expression of SgNramp1 complemented the phenotype of the Mn uptake-defective yeast (Saccharomyces cerevisiae) mutant Δsmf1. Mn concentration in the yeast cells expressing SgNramp1 was higher than that of the empty vector control, suggesting the transport activity of SgNramp1 for Mn in yeast. Taken together, this study reveals that SgNramp1 is a plasma membrane-localized transporter responsible for Mn uptake in stylo.

Machine learning identification of cuproptosis and necroptosis-associated molecular subtypes to aid in prognosis assessment and immunotherapy response prediction in low-grade glioma.

Both cuproptosis and necroptosis are typical cell death processes that serve essential regulatory roles in the onset and progression of malignancies, including low-grade glioma (LGG). Nonetheless, there remains a paucity of research on cuproptosis and necroptosis-related gene (CNRG) prognostic signature in patients with LGG. We acquired patient data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) and captured CNRGs from the well-recognized literature. Firstly, we comprehensively summarized the pan-cancer landscape of CNRGs from the perspective of expression traits, prognostic values, mutation profiles, and pathway regulation. Then, we devised a technique for predicting the clinical efficacy of immunotherapy for LGG patients. Non-negative matrix factorization (NMF) defined by CNRGs with prognostic values was performed to generate molecular subtypes (i.e., C1 and C2). C1 subtype is characterized by poor prognosis in terms of disease-specific survival (DSS), progression-free survival (PFS), and overall survival (OS), more patients with G3 and tumour recurrence, high abundance of immunocyte infiltration, high expression of immune checkpoints, and poor response to immunotherapy. LASSO-SVM-random Forest analysis was performed to aid in developing a novel and robust CNRG-based prognostic signature. LGG patients in the TCGA and GEO databases were categorized into the training and test cohorts, respectively. A five-gene signature, including SQSTM1, ZBP1, PLK1, CFLAR, and FADD, for predicting OS of LGG patients was constructed and its predictive reliability was confirmed in both training and test cohorts. In both the training and the test datasets (cohorts), higher risk scores were linked to a lower OS rate. The time-dependent ROC curve proved that the risk score had outstanding prediction efficiency for LGG patients in the training and test cohorts. Univariate and multivariate Cox regression analyses showed the CNRG-based prognostic signature independently functioned as a risk factor for OS in LGG patients. Furthermore, we developed a highly reliable nomogram to facilitate the clinical practice of the CNRG-based prognostic signature (AUC > 0.9). Collectively, our results gave a promising understanding of cuproptosis and necroptosis in LGG, as well as a tailored prediction tool for prognosis and immunotherapeutic responses in patients.

Comparison of the Reproductive Outcome Between 2 and 4 mg Daily Doses of Estradiol After Hysteroscopic Adhesiolysis: A Propensity Score Matching Analysis-Retrospective Cohort Study.

Objective: To investigate the effect of two postoperative doses of estradiol valerate (2 and 4 mg/day) on reproductive outcomes in patients with moderate to severe intrauterine adhesions (IUAs). Methods: A retrospective cohort study was conducted at a single tertiary reproductive medical center between January 2018 and December 2019 to compare the reproductive outcomes of two doses of estradiol valerate (2 and 4 mg daily) after hysteroscopic adhesiolysis. All patients received adjuvant postoperative treatment with a Foley catheter, hyaluronic acid gel, and medication therapy. Hysteroscopy was repeated every 7 days after surgery. Multivariate regression analysis and propensity score matching (PSM) were performed to minimize intrinsic bias. Results: A total of 212 patients with moderate to severe IUAs were included: 74 patients received 2 mg of estradiol valerate daily and 138 patients received 4 mg of estradiol daily postoperatively. No significant differences were found in the reproductive outcomes between the two groups, including clinical pregnancy rates. The multivariable regression analyses both before and after PSM also showed that there was no significant difference in the menstrual improvement and clinical pregnancy rates between the two groups. Conclusions: We suggest the use of a lower dose (2 mg/day) of estradiol valerate as an adjuvant therapy for IUAs to minimize estrogen-related side effects.

Invasive treatment strategy in patients aged 80 years or older with non-ST-elevation acute coronary syndromes: a retrospective cohort study.

Background: Invasive treatment is commonly recommended for patients with non-ST-elevation acute coronary syndromes (NSTE-ACS). However, the efficacy of this approach in patients aged ≥80 years remains uncertain. Methods: We retrospectively assessed consecutive NSTE-ACS patients ≥80 years of age who were hospitalized at our cardiovascular center from December 2012 to July 2019. Patients were divided into two groups based on whether they received invasive treatment (coronary angiography and, if indicated, revascularization) or not. Patients who died in the first 3 days after admission without receiving invasive treatment were excluded. The effect of invasive timed treatment was also explored by dividing patients into timely invasive or delayed invasive groups according to their risk classification. Multivariate COX regression, invasive probability weighting and propensity score matching were used to adjust for confounding variables. The primary outcome was all-cause death during follow-up. Results: A total of 1,201 patients with a median age of 82.0 (IQR, 81.0-84.0) were divided into two groups: 656 (54.6%) patients in the invasive group and 545 (45.4%) patients in the conservative group. Follow-up survival information was available for up to 6 years (median 3.0 years). During the follow-up, 296 (24.6%) patients died. After adjusting for confounding variables, the invasive treatment strategy was significantly associated with a lower risk of long-term mortality (HR =0.70, 95% CI: 0.54-0.92, P=0.010). No difference was found between timely invasive and delayed invasive interventions with mortality (HR =0.92, 95% CI: 0.57-1.47, P=0.725). Conclusions: Invasive treatment was associated with lower mortality in patients ≥80 years of age with NSTE-ACS over a median of a 3-year follow-up. The invasive intervention time did not impact the outcome.

Serum Neuroglobin as a Potential Prognostic Biomarker for Cognitive Impairment After Intracerebral Hemorrhage.

Objective: Stroke is closely related to dementia, but there are few prospective studies on cognitive decline after stroke in patients with cerebral hemorrhage. Neuroglobin is an oxygen-binding protein mainly expressed in brain neurons. The aim of our current study was to determine whether neuroglobin could serve as a biomarker for cognitive prognosis in patients with intracerebral hemorrhage (ICH). Methods: Three hundred and sixteen patients with ICH were consecutively enrolled in a prospective study. Baseline data such as age and gender of ICH patients on admission were recorded. Serum neuroglobin concentrations were determined by enzyme-linked immunosorbent assay (ELISA). All ICH patients 3 months after onset were divided into post-stroke cognitive impairment group (PSCI) and non-PSCI group according to MoCA assessment results. Results: The PSCI and Non-PSCI groups had serum neuroglobin concentrations of (4.7 ± 0.9) and (7.5 ± 1.1) ng/ml, respectively, with a statistically significant difference between the two groups (p < 0.05). Age, gender, LDL, FBG, SBP, DBP, NHISS, and Hematoma volume were found to be adversely connected with MoCA (p < 0.05), while education, HDL, and serum neuroglobin were found to be positively correlated with MoCA (p < 0.05). After controlling for baseline data, regression analysis revealed that serum neuroglobin was remained an efficient biomarker for predicting cognitive performance in individuals with ICH (p < 0.05). The diagnostic accuracy of blood neuroglobin concentration for PSCI in ICH patients was 72.6%, the sensitivity was 67.4%, and the specificity was 75.5%, according to receiver operating characteristic (ROC) curve analysis. Conclusions: Serum neuroglobin may serve as a potential biomarker to predict cognitive decline after ICH.

Early Symptomatic Improvement After Ustekinumab Therapy in Patients With Ulcerative Colitis: 16-Week Data From the UNIFI Trial.

BACKGROUND & AIMS: Rapid symptomatic relief is an important treatment goal for patients with ulcerative colitis (UC). We aimed to characterize early response with ustekinumab in patients with moderate-to-severe UC during the initial 16 weeks of treatment. METHODS: We performed a post hoc analysis of data from A Study to Evaluate the Safety and Efficacy of Ustekinumab Induction and Maintenance Therapy in Participants With Moderately to Severely Active Ulcerative Colitis trial. Patients (N = 961) were randomized (1:1:1) to receive intravenous 130 mg ustekinumab, approximately 6 mg/kg ustekinumab, or placebo at week 0. Symptomatic remission, absolute stool number, Mayo stool frequency and rectal bleeding subscores, partial Mayo score, C-reactive protein, and fecal calprotectin were assessed in the overall population and for patients in the biologic-naïve or prior biologic failure subgroups. RESULTS: A significantly greater percentage of patients in the 130-mg ustekinumab (20.0%; P = .015) or approximately 6-mg/kg ustekinumab (20.2%; P = .012) groups achieved symptomatic remission at week 2 vs placebo (12.9%). Mean [SD] changes from baseline in daily stool number on day 7 were greater in the ustekinumab groups (-1.1 [2.6] in 130 mg [P = .065] and -1.2 [2.5] in ∼6 mg/kg [P = .017]) vs placebo (-0.7 [2.7]). The percentage of patients with Mayo stool frequency subscore of 1 or less and rectal bleeding subscore of 0 increased from baseline through week 16 for both ustekinumab groups. Significant improvements in partial Mayo scores were observed by week 2 in both ustekinumab groups vs placebo (P ≤ .001). Significantly more patients in the ustekinumab groups had normalized C-reactive protein levels from week 2 to week 8 vs placebo (P ≤ .05). Similar results were observed with normalized fecal calprotectin levels between week 2 and week 4 (P ≤ .05). CONCLUSIONS: Ustekinumab improved symptoms in patients with UC compared with placebo in as early as 7 days, indicating rapid onset of effect after induction. CLINICAL TRIAL REGISTRY NUMBER: ClinicalTrials.gov: NCT02407236.

Efficacy and Safety of Maintenance Ustekinumab for Ulcerative Colitis Through 3 Years: UNIFI Long-term Extension.

BACKGROUND AND AIMS: The UNIFI long-term extension [LTE] study reports the efficacy and safety of subcutaneous 90 mg ustekinumab through 3 years of maintenance therapy. METHODS: Patients randomised to ustekinumab every 12 weeks [q12w] or every 8 weeks [q8w] at maintenance baseline [N = 348] and randomised ustekinumab-treated patients in the LTE [N = 284] were evaluated. Symptomatic remission [Mayo stool frequency = 0/1, rectal bleeding = 0] was assessed. Safety included all LTE patients [N = 188 placebo and N = 457 ustekinumab]. RESULTS: Among patients randomised to the ustekinumab q12w and q8w groups at maintenance baseline, 54.1% and 56.3% achieved symptomatic remission at Week 152, respectively. Overall, 20% of patients discontinued ustekinumab, 10% of biologic-naïve and 30% of biologic-exposed patients. Among patients in symptomatic remission at Year 3, 94.6% and 98.0% of patients were also corticosteroid free, respectively. Corticosteroid-free symptomatic remission rates in the ustekinumab q12w and q8w groups were 51.2% and 55.1% at Week 152, respectively. Remission rates were higher for biologic-naïve patients than for those with a history of biologic failure. Biochemical evidence of response was demonstrated by stable, decreased C-reactive protein and faecal calprotectin measurements over 3 years. From Weeks 96 to 156, no deaths, major adverse cardiovascular events, or tuberculosis occurred. Nasopharyngitis, ulcerative colitis, and upper respiratory tract infection were most frequently reported. One ustekinumab-treated patient with a history of basal cell carcinoma [BCC] reported two BCCs. One patient in the q8w ustekinumab group, who was receiving concomitant 6-mercaptopurine, experienced serious adverse events of neutropenic sepsis and oral herpes. CONCLUSIONS: Efficacy of ustekinumab in patients with ulcerative colitis was confirmed through 3 years. No new safety signals were observed.

Surgical treatment of delayed cervical infection and incomplete quadriplegia with fish-bone ingestion: A case report.

BACKGROUND: The most commonly ingested foreign body in Asians is fish bone. The vast majority of patients have obvious symptoms and can be timely diagnosed and treated. Cases of pyogenic cervical spondylitis and diskitis with retropharyngeal and epidural abscess resulting in incomplete quadriplegia due to foreign body ingestion have been rarely reported. The absence of pharyngeal or esophageal discomfort and negative computed tomography (CT) findings of fish bone have not been reported. We report the case of an elderly female patient with delayed cervical infection and incomplete quadriplegia who had a history of fish bone ingestion. CASE SUMMARY: A 73-year-old woman presented with right neck pain and weakness of four limbs for a week, and had a history of fish bone ingestion and negative findings on laryngoscopic examination one month previously. She did not complain of any pharyngeal or esophageal discomfort. Cervical magnetic resonance imaging showed C4/C5 spondylitis and diskitis along with retropharyngeal and ventral epidural abscesses. No sign of fish bone was detected on lateral cervical radiography and CT scans. The muscle strength of the patient's right lower limb receded to grade 1 and other limbs to grade 2 suddenly on the 10th day of hospitalization. Emergency surgery was performed to drain the abscess and decompress the spinal cord by removing the anterior inflammatory necrotic tissue. Simultaneously, flexible esophagogastroduodenoscopy was carried out and a hole in the posterior pharyngeal wall was found. The motor weakness of the right lower limb improved to grade 3 and the other limbs to grade 4 within 2 d postoperatively. CONCLUSION: This rare case highlights the awareness of the posterior pharyngeal or esophageal wall perforation in patients with cervical pyogenic spondylitis along with a history of fish bone ingestion, even though local discomfort symptoms are absent and the radiological examinations are negative.

The Effect of Shaoyao Gancao Decoction on Sphincter of Oddi Dysfunction in Hypercholesterolemic Rabbits via Protecting the Enteric Nervous System-Interstitial Cells of Cajal-Smooth Muscle Cells Network.

OBJECTIVE: This study observes the morphological changes in the enteric nervous system (ENS) - interstitial cells of Cajal (ICC) - smooth muscle cells (SMC) network in sphincter of Oddi dysfunction (SOD) in hypercholesterolemic rabbits following treatment with Shaoyao Gancao decoction (SGD), as well as the apoptosis of the ICC. METHODS: In this study, 48 healthy adult New Zealand rabbits are randomly divided into three groups (n = 16 in each group): the control, the model, and the SGD treatment groups. The hypercholesterolemic rabbit model is established. Hematoxylin and eosin staining, transmission electron microscopy, immunofluorescence, terminal deoxynucleotidyl transferase dUTP nick end labeling staining, immunohistochemistry, Western blot analysis, and reverse transcription-polymerase chain reaction are used to detect the morphological changes in the ENS-ICC-SMC network, the expression of apoptosis-related proteins in the ICC, and to observe the curative effect of SGD after treatment. RESULTS: Compared with the control group, the morphology and the ultrastructure of the SO are destroyed in the model group. In addition, the protein gene product 9.5 (PGP9.5), nitric oxide (NO), the SMCs, and the ICC all significantly decreased while substance P (SP) significantly increased. Compared with the model group, the SO morphology and ultrastructure are repaired in the SGD group. In addition, the PGP9.5, NO, the SMCs, and the ICC significantly increased while SP decreased. In addition, SGD may activate the stem cell factor (SCF)/c-Kit signaling pathway to treat SO dysfunction by up-regulating the expression of c-Kit and SCF. Similarly, this pathway restores SO by up-regulating the expression of Bcl2 and inhibiting cleaved caspase-3, Bax, and the tumor necrosis factor. CONCLUSION: Shaoyao Gancao decoction can promote the recovery of sphincter of Oddi dysfunction in hypercholesterolemic rabbits by protecting the ENS-ICC-SMC network.

Serum Neuropeptide Y: A Potential Prognostic Marker of Intracerebral Hemorrhage.

OBJECTIVE: Neuropeptide Y (NPY), a 36-amino acid neuromodulator, is mainly secreted by neurons in the central and peripheral nervous systems, which participate in the regulation of a series of physiological processes. However, there are few studies on its correlation with intracranial hemorrhage (ICH). The purpose of this study is to determine whether the serum NPY level is related to the prognosis of ICH. METHODS: 364 patients diagnosed with ICH were included in the current study. The demographics, anthropometrics, medical history, clinical severity, and laboratory data are collected. Enzyme-linked immunoassay (ELISA) was used to detect the serum NPY level of each patient upon admission. Three months after the occurrence of ICH, we used the modified Rankin scale (mRS) to evaluate the prognosis of patients, and mRS > 2 was defined as a poor prognosis. RESULTS: A total of 364 patients with ICH were included in the study, including 140 patients with a good prognosis and 224 patients with a poor prognosis. Compared with patients with a poor prognosis, ICH patients with a good prognosis have a lower baseline National Institutes of Health Stroke Scale (NIHSS) score (p = 0.036) and smaller hematoma volume (p = 0.039). The results of ELISA showed that compared with patients with a poor prognosis, ICH patients with a good prognosis had lower serum NPY levels (19.4 ± 3.7 vs. 27.6 ± 3.3 ng/ml, p < 0.001). Linear correlation analysis showed that the serum NPY level of ICH patients was significantly positively correlated with the baseline NIHSS score (r = 0.413, p = 0.041) and hematoma volume (r = 0.308, p = 0.026). Receiver operating characteristic (ROC) curve analysis showed that the sensitivity of the serum NPY level to predict the prognosis of ICH was 70.9%, the specificity was 72.6%, and the cut-off value was 24.2 ng/ml. CONCLUSIONS: The serum NPY level may be used as a predictor of ICH prognosis.

IL-33 as a Novel Serum Prognostic Marker of Intracerebral Hemorrhage.

OBJECTIVE: Interleukin 33 (IL-33) is a key cytokine involved in inflammation and oxidative stress. The significance of serum IL-33 levels on the prognosis of patients with intracerebral hemorrhage (ICH) has not been well studied. The purpose of this study is to determine whether there is a relationship between the serum IL-33 level and the prognosis of patients with ICH upon admission. METHODS: A total of 402 patients with confirmed ICH were included in this study. Their demographic data, medical history, laboratory data, imaging data, and clinical scores on admission were collected. At the same time, enzyme-linked immunoassay (ELISA) was used to detect the serum IL-33 levels of patients. The prognosis of patients was evaluated by mRS scale after 3 months, and mRS > 2 was defined as poor prognosis. RESULTS: Among 402 patients with ICH, the number of patients with good prognosis and poor prognosis after 3 months was 148 and 254, respectively. Compared with the ICH group with poor prognosis, the ICH group with good prognosis had lower baseline NHISS scores (p = 0.039) and hematoma volume (p = 0.025) and higher GCS scores (p < 0.001) and serum IL-33 levels (p < 0.001). The results of linear correlation analysis showed that serum IL-33 levels were significantly negatively correlated with baseline NHISS scores (r = -0.224, p = 0.033) and hematoma volume (r = -0.253, p = 0.046) but were significantly positively correlated with baseline GCS scores (r = 0.296, p = 0.020). The receiver operating characteristic curve (ROC) analysis showed that the sensitivity and specificity of serum IL-33 level in evaluating the prognosis of ICH were 72.1% and 74.3%, respectively. A cut-off value of serum IL-33 level < 109.3 pg/mL may indicate a poor prognosis for ICH. CONCLUSIONS: Serum IL-33 level on admission may be a prognostic indicator of ICH, and its underlying mechanism needs further study.