Activation of nuclear factor erythroid 2-related factor 2(Nrf2)by Kelch-like ECH-associated protein 1(Keap1)alkylation plays a central role in anti-inflammatory therapy.However,activators of Nrf2 through alkylation of Keap1-Kelch domain have not been identified.Deoxynyboquinone(DNQ)is a natural small molecule discovered from marine actinomycetes.The current study was designed to investigate the anti-inflammatory effects and molecular mechanisms of DNQ via alkylation of Keap1.DNQ exhibited signif-icant anti-inflammatory properties both in vitro and in vivo.The pharmacophore responsible for the anti-inflammatory properties of DNQ was determined to be the α,β-unsaturated amides moieties by a chemical reaction between DNQ and N-acetylcysteine.DNQ exerted anti-inflammatory effects through activation of Nrf2/ARE pathway.Keap1 was demonstrated to be the direct target of DNQ and bound with DNQ through conjugate addition reaction involving alkylation.The specific alkylation site of DNQ on Keap1 for Nrf2 activation was elucidated with a synthesized probe in conjunction with liquid chromatography-tandem mass spectrometry.DNQ triggered the ubiquitination and subsequent degra-dation of Keap1 by alkylation of the cysteine residue 489(Cys489)on Keap1-Kelch domain,ultimately enabling the activation of Nrf2.Our findings revealed that DNQ exhibited potent anti-inflammatory capacity through α,β-unsaturated amides moieties active group which specifically activated Nrf2 signal pathway via alkylation/ubiquitination of Keap1-Kelch domain,suggesting the potential values of targeting Cys489 on Keap1-Kelch domain by DNQ-like small molecules in inflammatory therapies.

OBJECTIVE: To investigate the risk factors of oral ulcers and bloodstream infection in patients with hematopoietic stem cell transplantation. METHODS: The clinical data of 401 hematopoietic stem cell transplant patients in the First Affiliated Hospital of Zhengzhou University from January 2020 to December 2021 were retrospective analyzed, and the risk factors of oral ulcers and bloodstream infection statistical and analyzed. RESULTS: Among the 401 patients, the incidence of oral ulcers was 61.3% (246/401), and the incidence of bloodstream infection was 9.0% (36/401). A total of 40 strains of pathogenic bacteria were isolated from 36 patients, including 26 strains of Gram negative strains (65%), 13 strains of Gram positive strains (32.5%), and 1 strain of fungi (2.5%). Single-factor analysis showed that oral hygiene was associated with the occurrence of bloodstream infection, and the Multi-factor analysis showed that age ≥14 years old, disease diagnosis of leukemia, and allogeneic hematopoietic stem cell transplantation were risk factors for oral ulcers. CONCLUSION The incidence of oral ulcers in patients with hematopoietic stem cell transplantation is high. The age ≥14 years, disease diagnosis of leukemia, and allogeneic hematopoietic stem cell transplantation were risk factors for oral ulcers in patients, and oral hygiene was associated with the occurrence of bloodstream infection.
Humans ; Adolescent ; Retrospective Studies ; Oral Ulcer/etiology* ; Bacteremia/microbiology* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Sepsis ; Risk Factors ; Leukemia

Objective:To explore the prevalence and risk factors of thyroid nodules in physical examination population.Method:A total of 5934 Han people who underwent physical examination in the physical examination center of the Affiliated Hospital of Hubei University of Arts and Sciences from August 2016 to August 2019 were selected as the research objects. Retrospective research methods were used to divide them into thyroid nodule group and thyroid non nodule group according to the results of thyroid ultrasound examination, and statistical analysis was carried out in combination with relevant data. T-test was used for the comparison between measurement data groups that conform to the normal distribution and χ 2 test was used for the comparison between counting data groups. Binary Logistic regression was used to analyze the relationship between different factors and thyroid nodules, and the odds ratio ( OR) and 95% confidence interval (95% CI) were calculated. Results:(1) The prevalence of thyroid nodules in all population is 28.1% (1 668/5 934), the prevalence of thyroid nodule is 23.1% (977/4 230) in men and 40.6% (691/1 704) in women separately, and the distribution is obviously higher in women than that in male (χ 2=183.13, P=0.008). The prevalence increased with aging in both sexes ( P=0.001). (2) The correlation between the clinical data of physical examination population and thyroid nodules was analyzed according to gender. Among male patients, the rates of BMI≥23.0 kg/m 2 (82.2% (803/977)), diabetes (14.7% (144/977)), hypertension (44.4% (434/977)) and smoking history (63.1% (616/977)) in thyriod nodule group were higher than those in the non thyroid nodule group (78.9% (2 565/3 253), 8% (260/3 253), 29.3% (952/3 253), 56.9% (1 851/3 253)) (χ 2 were 5.17, 39.59, 78.35 and 11.80, respectively; P values were 0.023, 0.009, 0.005 and 0.007, respectively). Among female patients, the rates of BMI ≥23.0 kg/m 2 (55% (380/691)), obesity (31.1% (215/691)), diabetes (6.2% (43/691)), hypertension (28.9% (200/691)), high total cholesterol (43.6% (301/691)), low high-density lipoprotein cholesterol (7.1% (49/691)), high triglycerides (28.4% (196/691)), and high low-density lipoprotein cholesterol (29.1% (201/691)) in thyroid nodule group were higher than those in the non thyroid nodule group (43.6% (442/1 013), 22.5% (228/1 013), 1.9% (19/1 013), 19.2% (195/1 013), 34.7% (352/1 013), 17.9% (181/1 013), 21.5% (218/1 013), 4.5% (46/1 013)), and the differences were statistically significant (χ 2 were 21.23, 15.82, 22.14, 21.68, 13.51, 26.27, 12.69 and 5.08, respectively; P values were 0.007, 0.006, 0.009, 0.007, 0.008, 0.005, 0.005 and 0.024, respectively). (3) Multiple logistic regression analysis reveal that age ( OR=1.530, 95% CI:1.463-1.621, P=0.009), sex ( OR=3.580, 95% CI:2.931-4.381, P=0.005), smoking ( OR=1.360, 95% CI:1.161-1.592, P=0.007) and high blood pressure ( OR=1.290, 95% CI:1.121-1.482, P=0.006) were the risk factors of thyroid nodule. Conclusion:The prevalence of thyroid nodules is 28.1% in XiangYang and surrounding areas, and the elders, women, smoking and high blood pressure were the risk factors of thyroid nodule.

Objective Coronavirus disease 2019 (COVID-19) and tuberculosis (TB) are major public health and social issues worldwide. The long-term follow-up of COVID-19 with pulmonary TB (PTB) survivors after discharge is unclear. This study aimed to comprehensively describe clinical outcomes, including sequela and recurrence at 3, 12, and 24 months after discharge, among COVID-19 with PTB survivors. Methods From January 22, 2020 to May 6, 2022, with a follow-up by August 26, 2022, a prospective, multicenter follow-up study was conducted on COVID-19 with PTB survivors after discharge in 13hospitals from four provinces in China. Clinical outcomes, including sequela, recurrence of COVID-19, and PTB survivors, were collected via telephone and face-to-face interviews at 3, 12, and 24 months after discharge. Results Thirty-two COVID-19 with PTB survivors were included. The median age was 52 (45, 59) years, and 23 (71.9％) were men. Among them, nearly two-thirds (62.5％) of the survivors were moderate, three (9.4％) were severe, and more than half (59.4％) had at least one comorbidity (PTB excluded). The proportion of COVID-19 survivors with at least one sequela symptom decreased from 40.6％ at 3 months to 15.8％ at 24 months, with anxiety having a higher proportion over a follow-up. Cough and amnesia recovered at the 12-month follow-up, while anxiety, fatigue, and trouble sleeping remained after 24 months. Additionally, one (3.1％) case presented two recurrences of PTB and no re-positive COVID-19 during the follow-up period. Conclusion The proportion of long symptoms in COVID-19 with PTB survivors decreased over time, while nearly one in six still experience persistent symptoms with a higher proportion of anxiety. The recurrence of PTB and the psychological support of COVID-19 with PTB after discharge require more attention.

Objective:To analyze the incidence and epidemiological characteristics of traumatic spinal cord injury in China in 2018.Methods:Multi-stage stratified cluster sampling was used to randomly select hospitals capable of treating patients with spinal cord injury from 3 regions，9 provinces and 27 cities in China to retrospectively investigate eligible patients with traumatic spinal cord injury admitted in 2018. National and regional incidence rates were calculated. The data of cause of injury，injury level，severity of injury，segment and type of fracture，complications，death and other data were collected by medical record questionnaire，and analyzed according to geographical region，age and gender.Results:Medical records of 4，134 patients were included in this study，with a male-to-female ratio of 2.99∶1. The incidence of traumatic spinal cord injury in China in 2018 was 50.484 / 1 million （95% CI 50.122-50.846）. The highest incidence in the Eastern region was 53.791 / 1 million （95% CI 53.217-54.365）. In the whole country，the main causes of injury were high falls （29.58%），as well as in the Western region （40.68%），while the main causes of injury in the Eastern and Central regions were traffic injuries （31.22%，30.10%）. The main injury level was cervical spinal cord in the whole country （64.49%），and the proportion of cervical spinal cord injury in the Central region was the highest （74.68%），and the proportion of lumbosacral spinal cord injury in the Western region was the highest （32.30%）. The highest proportion of degree of injury was incomplete quadriplegia （55.20%），and the distribution pattern was the same in each region. A total of 65.87% of the patients were complicated with fracture or dislocation，77.95% in the Western region and only 54.77% in the Central region. In the whole country，the head was the main combined injury （37.87%），as well as in the Eastern and Central regions，while the proportion of chest combined injury in the Western region was the highest （38.57%）. A total of 32.90% of the patients were complicated with respiratory complications. There were 23 patients （0.56%） died in hospital，of which 17（73.91%） died of respiratory dysfunction. Conclusions:The Eastern region of China has a high incidence of traumatic spinal cord injury. Other epidemiological features include high fall as the main cause of injury cervical spinal cord injury as the main injury level，incomplete quadriplegia as the main degree of injury，head as the main combined injury，and respiratory complications as the main complication.

Betacoronavirus ; China ; epidemiology ; Coronavirus Infections ; prevention & control ; Disease Outbreaks ; Emergencies ; Hospitals, General ; Humans ; Internet ; Pandemics ; prevention & control ; Pneumonia, Viral ; prevention & control

Objective: To evaluate the inter-bottle variations, stability in consumption and interchangeability of unassayed biochemistry serum controls. Methods: Comparison between unassayed serum controls from a domestic "Pretrol^®" and an international "Bio-Rad" manufacturer was conducted in department of laboratory, in May 2016, with Roche Cobas 8000, Roche Hitachi 7600 and Siemens 2400 modular analyzer. The inter-bottle variation was determined by monitoring the inter-batch variation of 10 bottles of control samples after eliminating the intra-batch variation from the same bottle. Stability in consumption was determined as the precision after 7 days storage under 2 ℃ to 8 ℃ or 30 days of storage under -20 ℃ since reconstitution. The interchangeability was determined as the precisionbetween the controls from different manufacturers for the same test. Results: The inter-bottle imprecision of controls from domestic manufacturer for 13 biochemistry tests (CV concentration 1/CV concentration 2) were potassium (0.26%/0.42%), sodium (0.26%/0.21%), phosphorus (0.00%/0.62%), cholesterol (0.56%/0.54%), total protein (0.52%/0.33%), albumin (0.44%/2.00%), alanine aminotransferase (1.72%/0.57%), γ-glutamylaminotransferase (0.52%/0.62%), aspartate aminotransferase (3.10%/1.09%), lactate dehydrogenase (0.76%/0.91%), alkaline phosphatase (1.13%/0.97%), amylase (0.30%/0.39%) and glucose (0.00%/0.40%). The stability in consumption of the controls from the domestic manufacturer (CV concentration 1/CV concentration 2 under 2 ℃ to 8 ℃storage; CV concentration 1/CV concentration 2 under -20 ℃ storage) were potassium (1.06%/0.36%; 0.74%/0.48%), sodium (0.49%/0.59%; 0.72%/0.65%), phosphorus (0.95%/0.80%; 1.43%/0.84%), cholesterol (1.49%/1.58%; 2.17%/1.80%), total protein (0.84%/0.75%; 1.60%/1.68%), albumin (1.33%/2.28%; 1.94%/2.43%), alanine aminotransferase (1.41%/0.51%; 3.24%/1.60%) γ-glutamylaminotransferase (1.16%/1.16%; 2.85%/2.49%), aspartate aminotransferase (4.37%/2.14%; 2.99%/1.31%), lactate dehydrogenase (2.70%/2.54%; 3.84%/2.97%), alkaline phosphatase (2.63%/1.96%; 2.31%/2.10%), amylase (0.95%/2.19%; 1.58%/1.38%) and glucose (0.60%/0.48%; 1.41%/1.55%). The Inter-bottle variation and stability in consumption of biochemistry test unassayed controls from the domestic manufacturer were compatible for clinical assay according to the CV% specification from the Clinical Biochemistry Test Quality Requirement (WS/T 403-2012). The imprecision of the controls from both the domestic and international manufacturers (CVp concentration 1/CVp concentration2; CVq concentration 1/CVq concentration 2) were potassium (0.52%/0.46%; 2.39%/0.47%), sodium (0.30%/0.17%; 0.81%/0.47%), phosphorus (2.72%/1.11%; 4.57%/2.07%), cholesterol (0.29%/1.38%; 2.94%/1.81%), total protein (0.66%/2.46%; 1.85%/2.54%), alkaline phosphatase (2.67%/4.66%; 3.58%/8.55%), total bilirubin (5.71%/5.09%; 9.55%/7.41%), albumin (1.10%/2.61%; 4.79%/1.93%), alanine aminotransferase (6.42%/1.25%; 5.74%/1.63%), γ-glutamylaminotransferase (2.27%/4.35%; 4.38%/0.74%), aspartate aminotransferase (0.56%/2.84%; 0.91%/2.11%) and lactate dehydrogenase (2.36%/2.47%; 3.10%/1.52%). The interchangeability of serum controls from domestic manufacturer was better than clinical serum samples. Conclusion The unassayed serum biochemistry test controls from domestic manufacturer are suitable for the intra-laboratory quality control and showed a promising compatibility for inter-laboratory quality control usage.

OBJECTIVEAnesthetic isoflurane plus surgery has been reported to induce cognitive impairment. The underlying mechanism and targeted intervention remain largely to be determined. Ginsenoside Rb1 was reported to be neuroprotective. We therefore set out to determine whether ginsenoside Rb1 can attenuate isoflurane/surgery-induced cognitive dysfunction via inhibiting neuroinflammation and oxidative stress.

METHODSFive-months-old C57BL/6J female mice were treated with 1.4% isoflurane plus abdominal surgery for two hours. Sixty mg/kg ginsenoside Rb1 were given intraperitoneally from 7 days before surgery. Cognition of the mice were assessed by Barnes Maze. Levels of postsynaptic density-95 and synaptophysin in mice hippocampus were measured by Western blot. Levels of reactive oxygen species, tumor necrosis factor-α and interleukin-6 in mice hippocampus were measured by ELISA.

RESULTSHere we show for the first time that the ginsenoside Rb1 treatment attenuated the isoflurane/surgery-induced cognitive impairment. Moreover, ginsenoside Rb1 attenuated the isoflurane/surgery-induced synapse dysfunction. Finally, ginsenoside Rb1 mitigated the isoflurane/surgery-induced elevation levels of reactive oxygen species, tumor necrosis factor-α and interleukin-6 in the mice hippocampus.

CONCLUSIONThese results suggest that ginsenoside Rb1 may attenuate the isoflurane/surgery-induced cognitive impairment by inhibiting neuroinflammation and oxidative stress pending future studies.

Anesthetics, Inhalation ; adverse effects ; Animals ; Cognition ; Cognitive Dysfunction ; etiology ; prevention & control ; Female ; Ginsenosides ; pharmacology ; Hippocampus ; drug effects ; Inflammation ; etiology ; prevention & control ; Isoflurane ; adverse effects ; Medicine, Chinese Traditional ; Mice ; Mice, Inbred C57BL ; Oxidative Stress ; Postoperative Complications ; etiology ; prevention & control ; Random Allocation ; Surgical Procedures, Operative ; adverse effects ; Synapses ; metabolism

BACKGROUNDAmyotrophic lateral sclerosis (ALS) and some mimic disorders, such as distal-type cervical spondylotic amyotrophy (CSA), Hirayama disease (HD), and spinobulbar muscular atrophy (SBMA) may present with intrinsic hand muscle atrophy. This study aimed to investigate different patterns of small hand muscle involvement in ALS and some mimic disorders.

METHODSWe compared the abductor digiti minimi/abductor pollicis brevis (ADM/APB) compound muscle action potential (CMAP) ratios between 200 ALS patients, 95 patients with distal-type CSA, 88 HD patients, 43 SBMA patients, and 150 normal controls.

RESULTSThe ADM/APB CMAP amplitude ratio was significantly higher in the ALS patients (P < 0.001) than that in the normal controls. The ADM/APB CMAP amplitude ratio was significantly reduced in the patients with distal-type CSA (P < 0.001) and the HD patients (P < 0.001) compared with that in the normal controls. The patients with distal-type CSA had significantly lower APB CMAP amplitude than the HD patients (P = 0.004). The ADM/APB CMAP amplitude ratio was significantly lower in the HD patients (P < 0.001) than that in the patients with distal-type CSA. The ADM/APB CMAP amplitude ratio of the SBMA patients was similar to that of the normal controls (P = 0.862). An absent APB CMAP and an abnormally high ADM/APB CMAP amplitude ratio (≥4.5) were observed exclusively in the ALS patients.

CONCLUSIONSThe different patterns of small hand muscle atrophy between the ALS patients and the patients with mimic disorders presumably reflect distinct pathophysiological mechanisms underlying different disorders, and may aid in distinguishing between ALS and mimic disorders.

Action Potentials ; Adult ; Aged ; Amyotrophic Lateral Sclerosis ; pathology ; physiopathology ; Diagnosis, Differential ; Female ; Hand ; pathology ; Humans ; Male ; Middle Aged ; Muscle, Skeletal ; physiopathology ; Muscular Atrophy ; pathology ; physiopathology ; Retrospective Studies ; Spinal Muscular Atrophies of Childhood ; pathology ; Spondylosis ; pathology

BACKGROUNDDysfunctional spinal circuit may play a role in the pathophysiology of amyotrophic lateral sclerosis (ALS). The purpose of this study was to use F waves for assessment of segmental motoneuronal excitability following upper motor neuron (UMN) dysfunctions in ALS.

METHODSWe studied the F waves of 152 ulnar nerves recorded from abductor digiti minimi in 82 patients with ALS. Two groups of hands were defined based on the presence or absence of pyramidal signs in the same upper limb. The group with pyramidal signs in the upper limbs was designated as the P group, and the group without pyramidal signs in the upper limbs was designated as the NP group.

RESULTSThe mean (P < 0.001), median (P < 0.001) and maximum (P = 0.035) F wave amplitudes, mean (P < 0.001), median (P < 0.001) and maximum (P = 0.003) F/M amplitude ratio, index repeating neuron (P < 0.001) and index repeater F waves (P < 0.001) of the P group were significantly increased compared with the NP group. No significant differences were identified for F wave chronodispersion (P = 0.628), mean F wave latency (P = 0.151), minimum F wave latency (P = 0.211), maximum F wave latency (P = 0.199), F wave persistence (P = 0.738), F wave duration (P = 0.152), F wave conduction velocity (P = 0.813) and number of giant F waves (P = 0.072) between the two groups.

CONCLUSIONSIn this study, increased F wave amplitude, F/M amplitude ratio and number of repeater F waves reflected enhanced segmental motoneuronal excitability following UMN dysfunctions in ALS.

Adult ; Aged ; Amyotrophic Lateral Sclerosis ; physiopathology ; Female ; Humans ; Male ; Middle Aged ; Motor Neuron Disease ; physiopathology ; Motor Neurons ; physiology ; Neural Conduction ; physiology ; Ulnar Nerve ; physiology