Lycium barbarian seed oil activates Nrf2/ARE pathway to reduce oxidative damage in testis of subacute aging rats / 中国药理学通报

Aim To explore the effects of Lycium berry seed oil on Nrf2/ARE pathway and oxidative damage in testis of subacute aging rats. Methods Fifty out of 60 male SD rats, aged 8 weeks, were subcutaneously injected with 125 mg • kg"D-galactosidase in the neck for 8 weeks to establish a subacute senescent rat model. The presence of senescent cells was observed using P-galactosidase ((3-gal), while testicular morphology was examined using HE staining. Serum levels of testosterone (testosterone, T), follicle-stimulating hormone ( follicle stimulating hormone, FSH ) , luteinizing hormone ( luteinizing hormone, LH ) , superoxide dis-mutase ( superoxide dismutase, SOD ) , glutathione ( glutathione, GSH) and malondialdehyde ( malondial-dehyde, MDA) were measured through ELISA, and the expressions of factors related to aging, oxidative damage, and the Nrf2/ARE pathway were assessed via immunohistochemical analysis and Western blotting. Results After successfully identifying the model, the morphology of the testis was improved and the intervention of Lycium seed oil led to a down-regulation in the expression of [3-gal and -yH2AX. The serum levels of SOD, GSH, T, and FSH increased while MDA and LH decreased (P 0. 05) . Additionally, there was an up-regulated expression of Nrf2, GCLC, NQOl, and SOD2 proteins in testicular tissue ( P 0. 05 ) and nuclear expression of Nrf2 in sertoli cells. Conclusion Lycium barbarum seed oil may reduce oxidative damage in testes of subacute senescent rats by activating the Nrf2/ARE signaling pathway.

Multisensory Conflict Impairs Cortico-Muscular Network Connectivity and Postural Stability: Insights from Partial Directed Coherence Analysis / 神经科学通报·英文版

Sensory conflict impacts postural control, yet its effect on cortico-muscular interaction remains underexplored. We aimed to investigate sensory conflict's influence on the cortico-muscular network and postural stability. We used a rotating platform and virtual reality to present subjects with congruent and incongruent sensory input, recorded EEG (electroencephalogram) and EMG (electromyogram) data, and constructed a directed connectivity network. The results suggest that, compared to sensory congruence, during sensory conflict: (1) connectivity among the sensorimotor, visual, and posterior parietal cortex generally decreases, (2) cortical control over the muscles is weakened, (3) feedback from muscles to the cortex is strengthened, and (4) the range of body sway increases and its complexity decreases. These results underline the intricate effects of sensory conflict on cortico-muscular networks. During the sensory conflict, the brain adaptively decreases the integration of conflicting information. Without this integrated information, cortical control over muscles may be lessened, whereas the muscle feedback may be enhanced in compensation.

Oral anti-coagulants use in Chinese hospitalized patients with atrial fibrillation / 中华医学杂志(英文版)

BACKGROUND@#Oral anti-coagulants (OAC) are the intervention for the prevention of stroke, which consistently improve clinical outcomes and survival among patients with atrial fibrillation (AF). The main purpose of this study is to identify problems in OAC utilization among hospitalized patients with AF in China.@*METHODS@#Using data from the Improving Care for Cardiovascular Disease in China-Atrial Fibrillation (CCC-AF) registry, guideline-recommended OAC use in eligible patients was assessed.@*RESULTS@#A total of 52,530 patients with non-valvular AF were enrolled from February 2015 to December 2019, of whom 38,203 were at a high risk of stroke, 9717 were at a moderate risk, and 4610 were at a low risk. On admission, only 20.0% (6075/30,420) of patients with a diagnosed AF and a high risk of stroke were taking OAC. The use of pre-hospital OAC on admission was associated with a lower risk of new-onset ischemic stroke/transient ischemic attack among the diagnosed AF population (adjusted odds ratio: 0.54, 95% confidence interval: 0.43-0.68; P  <0.001). At discharge, the prescription rate of OAC was 45.2% (16,757/37,087) in eligible patients with high stroke risk and 60.7% (2778/4578) in eligible patients with low stroke risk. OAC utilization in patients with high stroke risk on admission or at discharge both increased largely over time (all P  <0.001). Multivariate analysis showed that OAC utilization at discharge was positively associated with in-hospital rhythm control strategies, including catheter ablation (adjusted odds ratio [OR] 11.63, 95% confidence interval [CI] 10.04-13.47; P <0.001), electronic cardioversion (adjusted OR 2.41, 95% CI 1.65-3.51; P <0.001), and anti-arrhythmic drug use (adjusted OR 1.45, 95% CI 1.38-1.53; P <0.001).@*CONCLUSIONS@#In hospitals participated in the CCC-AF project, >70% of AF patients were at a high risk of stroke. Although poor performance on guideline-recommended OAC use was found in this study, over time the CCC-AF project has made progress in stroke prevention in the Chinese AF population.Registration:ClinicalTrials.gov, NCT02309398.

Effects of Different Tidal Volumes and PEEPs on Cardiac Output in Pigs Measured by Pulmonary Artery Catheter， Pulse Contour Analysis and Transpulmonary Thermodilution / 中山大学学报(医学科学版)

ObjectiveTo compare the effects of different tidal volumes and positive end expiratory pressures （PEEPs） during mechanical ventilation on the cardiac output of pigs measured by pulmonary artery catheter， transpulmonary thermodilution and pulse contour analysis， and to explore their consistency in cardiac output determination. MethodsTwelve experimental pigs were selected and randomly divided into 3 groups， with 4 pigs in each. Cardiac output was measured by different methods， control group by pulmonary artery catheter， group A by transpulmonary thermodilution and group B by pulse contour analysis. Then we compared the effects of different tidal volumes and PEEPs on the cardiac output of pigs and to explore the consistency. The correlation coefficient between pulse contour analysis and pulmonary artery catheter was r=0.754， and they were positively correlated. The correlation coefficient between transpulmonary thermodilution and pulmonary artery catheter was r=0.771， and they were positively correlated. In determining cardiac output， pulse contour analysis was consistent with pulmonary artery catheter， with a relative error of 13.5% between them； transpulmonary thermodilution was consistent with pulmonary artery catheter， with a relative error of 12.9% between them. The cardiac output decreased significantly along with the increase of tidal volumes or PEEPs and the differences were statistically significant （P<0.05） ConclusionPulmonary artery catheter， transpulmonary thermodilution and pulse contour analysis are well consistent with each other in measuring the cardiac output of pigs. The pigs’cardiac output gradually decreased along with the increase of tidal volumes or PEEPs during mechanical ventilation.

Precise Clinical Positioning of Chinese Patent Medicine in Paradigm of "Target Spectral Effect of Prescription"： A Case Study of Qizhi Tongluo Capsules / 中国实验方剂学杂志

The clinical value of Chinese patent medicine is the core direction of the development of the traditional Chinese medicine industry. The precise clinical positioning determines the way to prove the value of the drug， and is a key link to highlight the clinical value. This paper presented a case study of clinical positioning for Chinese patent medicine， namely Qizhi Tongluo capsules， and the key technical framework of precise clinical positioning of Chinese patent medicine， which was manifested as a comparison of prescription target spectral effect， discovery of core value of prescription， and confirmation of clinical positioning trial. The technical framework was designed to address a range of issues in the realm of precise clinical positioning. Before the clinical positioning trial， based on the multi-component， multi-target， and multi-phenotype data of prescription and clinical indication， the multi-omics network analysis technology was used to identify the core value of the traditional Chinese medicine varieties and predict the potential clinical advantages. Then， based on the predicted clinical advantages， reasonable efficacy indicators were selected， and the clinical efficacy was judged and verified by dynamic and flexible innovative clinical trials to improve the success rate of clinical positioning. This research paradigm integrates "omics technology" with "evidence-based" principles and follows the "precise evidence-based" concept. This research aims to provide a new strategy and method for the precise medication and positioning of Chinese patent medicine with traditional Chinese medicine characteristics after being put into the market and provide more technical thinking for traditional Chinese medicine to move towards precise medicine.

Genetic analysis of two children with Coffin-Siris syndrome due to variants of ARID1B gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis of two children with unexplained psychomotor developmental delay and facial dysmorphisms suggestive of Coffin-Siris syndrome (CSS).@*METHODS@#A boy and a girl suspected for CSS at the 980th Hospital of the People's Liberation Army Joint Service Support Force respectively in July 2019 and January 2021, and seven members from their families, were selected as the study subjects. Clinical data and family history of the children were collected, and detailed physical examination was carried out, in addition with laboratory and related auxiliary examinations. Potential variants and copy number variations (CNVs) were detected by whole exome sequencing (WES) and copy number variation sequencing (CNV-seq).@*RESULTS@#Child 1, an 8-month-old female, had featured microcephaly, atrial septal defect, curving of fifth finger/toe, and low limb muscle tone. Child 2 was a 2.5-year-old male with language delay, social impairment, dense hair but no curving of the fifth fingers. Genetic testing revealed that child 1 had loss of heterozygosity for exons 8 to 21 of the ARID1B gene, which was unreported previously. Family verification showed that both of her parents were of the wild type. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG) and American Society of Molecular Pathology (AMP), the variant was rated as pathogenic (PVS1+PS2+PM2-supporting). Child 2 was found to harbor a heterozygous c.4263-6 (IVS17) T>G variant of the ARID1B gene. Transcriptome sequencing confirmed that the variant can affect the normal splicing, resulting in retention of a 5 bp sequence in intron 17. Family verification showed that both of his parents were of the wild type. Based on the guidelines from the ACMG, the variant was rated as pathogenic (PS2+PM2-supporting+PP3+PS3).@*CONCLUSION@#WES and RNA-seq have confirmed the diagnosis of CSS in both children. Discovery of the novel variants has expanded the spectrum of pathogenic mutations underlying CSS, and provided a basis for the genetic counseling.

Herniation of intervertebral disc into thoracolumbar fracture vertebral body leads to malunion of fracture and decrease of intervertebral space height / 中国骨伤

OBJECTIVE@#To analyze the clinical characteristics of intervertebral disc tissue injury and herniation into the vertebral body in thoracolumbar fracture on fracture healing, vertebral bone defect volume and intervertebral space height.@*METHODS@#From April 2016 to April 2020, a total of 140 patients with thoracolumbar single vertebral fracture combined with upper intervertebral disc injury treated with pedicle screw rod system reduction and internal fixation in our hospital. There were 83 males and 57 females, aged from 19 to 58 years old, with an average age of (39.33±10.26) years old. All patients were followed up regularly 6 months, 12 months and 18 months after surgery. The patients with injured intervertebral disc tissue not herniated into the fractured vertebral body were the control group, and the patients with injured intervertebral disc and herniated into the fractured vertebral body were the observation group. By detecting the thoracolumbar AP and lateral X-ray films, CT and MRI of the thoracolumbar segment at different follow-up time, calculate the changes of the wedge angle of the fractured vertebral body, the sagittal kyphosis angle and the height of the superior adjacent intervertebral space, the changes of the fracture healing and bone defect volume after the reduction of the vertebral body, and the changes of the intervertebral disc degeneration grade. The prognosis was evaluated by visual analogue scale(VAS) and Oswestry disability index(ODI). Finally, the differences of the above results among different groups were comprehensively analyzed.@*RESULTS@#All the patients had normal wound healing without complications. A total of 87 patients received complete follow-up data, at least 18 months after internal fixation. Thoracolumbar AP and lateral X-ray films showed that 18 months after the reduction and internal fixation operation, the vertebral wedge angle, sagittal kyphosis angle and the height of the upper adjacent intervertebral space in the observation group were greater than those in the control group(P<0.05). CT scanning showed that the deformity of the fracture healed 12 months after the vertebral body reduction in the observation group and formed a "cavity" of bone defect connected with the intervertebral space, and its volume was significantly increased compared with that before (P<0.05). MRI scanning showed that the degeneration rate of injured intervertebral discs in the observation group was more serious than that in the control group 12 months after operation(P<0.05). However, there was no significant difference in VAS and ODI score at each time.@*CONCLUSION@#Herniation of injured intervertebral disc tissue hernias into the fractured vertebral body leads to increased bone resorption defect volume around the fracture and forms a malunion "cavity" connected with the intervertebral space. This may be the main reason for the change of vertebral wedge angle, the increase of sagittal kyphosis angle and the decrease of intervertebral space height after removal of internal fixation devices.

Progress on the mechanism of n-hexane induced toxic effects in vitro and in vivo / 中华劳动卫生职业病杂志

Hexane is a widely used organic solvent in industry, and chronic hexane poisoning is the main occupational toxic lesion in China. In particular, axonal and myelin lesions in the distal thick fibers of the peripheral nervous system may be caused by 2, 5-hexanedione (2, 5-HD), an intermediate metabolite of n-hexane in humans. Hexane has toxic effects not only on the nervous system but also on the liver, kidneys, and reproductive organs. In this paper, we review the progress of research on the mechanism of n-hexane toxic neuropathy.

Clinical features of 6 children with uridine-responsive developmental epileptic encephalopathy 50 caused by CAD gene variants / 中华儿科杂志

Objective: To analyze the clinical features of children with uridine responsive developmental epileptic encephalopathy 50 (DEE50) caused by CAD gene variants. Methods: A retrospective study was conducted on 6 patients diagnosed with uridine-responsive DEE50 caused by CAD gene variants at Beijing Children's Hospital and Peking University First Hospital from 2018 to 2022. The epileptic seizures, anemia, peripheral blood smear, cranial magnetic resonance imaging (MRI), visual evoked potential (VEP), genotype features and the therapeutic effect of uridine were descriptively analyzed. Results: A total of 6 patients, including 3 boys and 3 girls, aged 3.5(3.2,5.8) years, were enrolled in this study. All patients presented with refractory epilepsy, anemia with anisopoikilocytosis and global developmental delay with regression. The age of epilepsy onset was 8.5 (7.5, 11.0) months, and focal seizures were the most common seizure type (6 cases). Anemia ranged from mild to severe. Four patients had peripheral blood smears prior to uridine administration, showing erythrocytes of variable size and abnormal morphology, and normalized at 6 (2, 8) months after uridine supplementation. Two patients suffered from strabismus, 3 patients had VEP examinations, indicating of suspicious optic nerve involvement, and normal fundus examinations. VEP was re-examined at 1 and 3 months after uridine supplementation, suggesting significant improvement or normalization. Cranial MRI were performed at 5 patients, demonstrating cerebral and cerebellar atrophy. They had cranial MRI re-examined after uridine treatment with a duration of 1.1 (1.0, 1.8) years, indicating significant improvement in brain atrophy. All patients received uridine orally at a dose of 100 mg/(kg·d), the age at initiation of uridine treatment was 1.0 (0.8, 2.5) years, and the duration of treatment was 2.4 (2.2, 3.0) years. Immediate cession of seizures was observed within days to a week after uridine supplementation. Four patients received uridine monotherapy and were seizure free for 7 months, 2.4 years, 2.4 years and 3.0 years respectively. One patient achieved seizure free for 3.0 years after uridine supplementation and had discontinued uridine for 1.5 years. Two patients were supplemented with uridine combined with 1 to 2 anti-seizure medications and had a reduced seizure frequency of 1 to 3 times per year, and they had achieved seizure free for 8 months and 1.4 years respectively. Conclusions: The clinical manifestations of DEE50 caused by CAD gene variants present a triad of refractory epilepsy, anemia with anisopoikilocytosis, and psychomotor retardation with regression, accompanied by suspected optic nerve involvement, all of which respond to uridine treatment. Prompt diagnosis and immediate uridine supplementation could lead to significant clinical improvement.

Evaluation of the efficacy and safety of Nocardia rubra cell wall skeleton immunotherapy for cervical high-risk HPV persistent infection / 中华妇产科杂志

Objective: To evaluate the efficacy and safety of Nocardia rubra cell wall skeleton (Nr-CWS) in the treatment of persistent cervical high-risk human papillomavirus (HR-HPV) infection. Methods: A randomized, double blind, multi-center trial was conducted. A total of 688 patients with clinically and pathologically confirmed HR-HPV infection of the cervix diagnosed in 13 hispital nationwide were recruited and divided into: (1) patients with simple HR-HPV infection lasting for 12 months or more; (2) patients with cervical intraepithelial neoplasia (CIN) Ⅰ and HR-HPV infection lasting for 12 months or more; (3) patients with the same HR-HPV subtype with no CINⅡ and more lesions after treatment with CINⅡ or CIN Ⅲ (CINⅡ/CIN Ⅲ). All participants were randomly divided into the test group and the control group at a ratio of 2∶1. The test group was locally treated with Nr-CWS freeze-dried powder and the control group was treated with freeze-dried powder without Nr-CWS. The efficacy and negative conversion rate of various subtypes of HR-HPV were evaluated at 1, 4, 8, and 12 months after treatment. The safety indicators of initial diagnosis and treatment were observed. Results: (1) This study included 555 patients with HR-HPV infection in the cervix (included 368 in the test group and 187 in the control group), with an age of (44.1±10.0) years. The baseline characteristics of the two groups of subjects, including age, proportion of Han people, weight, composition of HR-HPV subtypes, and proportion of each subgroup, were compared with no statistically significant differences (all P>0.05). (2) After 12 months of treatment, the effective rates of the test group and the control group were 91.0% (335/368) and 44.9% (84/187), respectively. The difference between the two groups was statistically significant (χ2=142.520, P<0.001). After 12 months of treatment, the negative conversion rates of HPV 16, 18, 52, and 58 infection in the test group were 79.2% (84/106), 73.3% (22/30), 83.1% (54/65), and 77.4% (48/62), respectively. The control group were 21.6% (11/51), 1/9, 35.1% (13/37), and 20.0% (8/40), respectively. The differences between the two groups were statistically significant (all P<0.001). (3) There were no statistically significant differences in vital signs (body weight, body temperature, respiration, pulse rate, systolic blood pressure, diastolic blood pressure, etc.) and laboratory routine indicators (blood cell analysis, urine routine examination) between the test group and the control group before treatment and at 1, 4, 8, and 12 months after treatment (all P>0.05); there was no statistically significant difference in the incidence of adverse reactions related to the investigational drug between the two groups of subjects [8.7% (32/368) vs 8.0% (15/187), respectively; χ2=0.073, P=0.787]. Conclusion: External use of Nr-CWS has good efficacy and safety in the treatment of high-risk HPV persistent infection in the cervix.

Immunogenicity and safety of revaccination of 23-valent pneumococcal polysaccharide vaccine in people aged 60 years and above / 中华流行病学杂志

Objective: To evaluate the immunogenicity and safety of revaccination of 23-valent pneumococcal polysaccharide vaccine (PPV23) in elderly people aged ≥60 years. Methods: The elderly aged ≥60 years with 1 dose of PPV23 vaccination were selected as revaccination group and those without history of pneumococcal vaccine immunization were selected as the first vaccination group. One dose of PPV23 was administered to both groups, and the first blood samples were collected before vaccination while the second blood samples were collected on day 28-40 after vaccination. ELISA was used to detect the concentrations of anti-specific serotype Streptococcus pneumoniae podocyte polysaccharide immunoglobulin G, and the safety of the vaccination was evaluated after 30 days. Results: The geometric mean concentration (GMC) of antibody to 23 serotypes before the vaccination (0.73-13.73 μg/ml) was higher in revaccination group than in the first vaccination group (0.39-7.53 μg/ml), the GMC after the vaccination (1.42-31.65 μg/ml) was higher than that before the vaccination (0.73-13.73 μg/ml) in the revaccination group, and the GMC after the vaccination (1.62-43.76 μg/ml) was higher than that before the vaccination (0.39-7.53 μg/ml) in the first vaccination group; the geometric mean growth multiple in revaccination group (2.16-3.60) was lower than that in the first vaccination group (3.86-16.13); The mean 2-fold antibody growth rate was lower in revaccination group (53.68%, 95%CI: 52.30%-55.06%) than in the first vaccination group (93.16%, 95%CI: 92.18%- 94.15%), all differences were significant (P<0.001). After the vaccination, 13 serotypes of GMC were higher in the first vaccination group than in revaccination group (P<0.001), the differences were not significant for 10 serotypes of GMC (P>0.05). The incidence of local adverse reaction was 19.20% and 13.27% in revaccination group and the first vaccination group, respectively (P=0.174). Conclusions: The antibody level in ≥60 years people who received one dose of PPV23 after a 5-year interval was still higher than that in unvaccinated people. The antibody level decreased after 5 years of the first vaccination, and the antibody level could be rapidly increased by one more dose vaccination, but the overall immune response was lower than that of the first vaccination; revaccination with PPV23 has a good safety.

Whole exome sequencing analysis and prenatal diagnosis in children with neurodevelopmental disorders / 中华预防医学杂志

To explore the application value of whole exome sequencing (WES) in the diagnosis of prenatal and postnatal neurodevelopmental disorders (NDDs). A total of 70 patients diagnosed with NDDs who underwent WES at the Medical Genetics Center of the Maternal and Child Health Hospital of Hubei Province between June 2020 and July 2021 were retrospectively analyzed. Genomic DNA was extracted from peripheral blood samples and amniotic fluid. WES-based copy number variant (CNV) analysis was integrated into the routine WES data analysis pipeline. The results showed that a molecular diagnosis rate could be made in 21/70 (30%) cases. Of 21 positive cases, 14 (23%) cases were detected by single-nucleotide variant/small insertion/deletion (SNV/Indel) analysis, of which 12 variants were novel, 6 (9.8%) cases were detected by WES-based CNV analysis, and 1 (1.6%) case was detected by a combination of both. The diagnostic yield of WES combined with CNV analysis was higher than that of SNV/Indel analysis alone (30%, 21/70 vs. 20%, 14/70). Of the 28 prenatally diagnosed cases, 6 cases were found to have inherited parental variation for NDDs, 10 cases were found not to have the same pathogenic variation as the proband, and the remaining 12 cases were found to have no pathogenic or likely pathogenic variation that could explain the NDDs phenotype. Clinical follow-up showed that 5 families opted for abortion and the remaining had no current abnormalities. In conclusion, WES may be an effective method to clarify the genetic etiology and prenatal diagnosis of NDDs, which is helpful in assessing the prognosis to aid clinical management and reproductive guidance.

Efficacy and safefy of Polymyxin B treatment for neutropenic patients suffering from refractory Gram-negative bacterial bloodstream infection / 中华血液学杂志

Objective: To assess the efficacy and safety of polymyxin B in neutropenic patients with hematologic disorders who had refractory gram-negative bacterial bloodstream infection. Methods: From August 2021 to July 2022, we retrospectively analyzed neutropenic patients with refractory gram-negative bacterial bloodstream infection who were treated with polymyxin B in the Department of Hematology of the First Affiliated Hospital of the Soochow University between August 2021 to July 2022. The cumulative response rate was then computed. Results: The study included 27 neutropenic patients with refractory gram-negative bacterial bloodstream infections. Polymyxin B therapy was effective in 22 of 27 patients. The median time between the onset of fever and the delivery of polymyxin B was 3 days [interquartile range (IQR) : 2-5]. The median duration of polymyxin B treatment was 7 days (IQR: 5-11). Polymyxin B therapy had a median antipyretic time of 37 h (IQR: 32-70). The incidence of acute renal dysfunction was 14.8% (four out of 27 cases), all classified as "injury" according to RIFLE criteria. The incidence of hyperpigmentation was 59.3%. Conclusion: Polymyxin B is a viable treatment option for granulocytopenia patients with refractory gram-negative bacterial bloodstream infections.

Pollution characteristics and health risk assessment of metals in farmland soil around the largest realgar mining area in Asia / 环境与职业医学

Background Heavy metal emissions from mining and smelting areas are a global problem, and health risks associated with heavy metal contamination of soils are of great concern. The long-term mining of the largest realgar mine in Asia has caused severe arsenic and other metal pollution to the surrounding rivers and soils. Objective To understand the levels of metal contamination and health risks in agricultural soils of villages surrounding the largest realgar mine in Asia, and to lay a good foundation for further necessary pollution control actions and decisions. Methods A field survey was conducted to collect soil samples according to the Technical rules for monitoring of environmental quality of farmland soil (NY/T 395-2012), and then inductively coupled plasma mass spectrometry was used to determine the contents of 28 heavy metals [cadmium (Cd), arsenic (As), lead (Pb), mercury (Hg), chromium (Cr), nickel (Ni), copper (Cu), zinc (Zn), beryllium (Be), selenium (Se), cobalt (Co), antimony (Sb), molybdenum (Mo), vanadium (V), barium (Ba), thallium (Tl), boron (B) , bismuth (Bi), lithium (Li), manganese (Mn), strontium (Sr), calcium (Ca), rubidium (Rb), iron (Fe), magnesium (Mg), aluminum (Al), kalium (K), and titanium (Ti)]. Geoaccumulation index, single factor pollution index, and Nemerow comprehensive index were used to evaluate the degree and characteristics of single metal pollution and combined pollution in soil, respectively. A health risk assessment model was used to evaluate the risks of metals in soil to human health. Results The results of geoaccumulation index calculation revealed that 22 heavy metals were enriched in the soil, and the indexes of target heavy metals from high to low were Cd > Se > Pb >Hg > As > Co> Ni > Cu > Zn > Bi > Sb > Mo > Be> Cr > Ba >V > Li > Sr> Mn> Rb > Ca> Tl . The single factor pollution indexes of 17 heavy metals from high to low were Be > Cd > B > Mo > V > As > Ni > Cu > Pb > Zn > Co > Se > Tl > Ba > Cr > Hg > Sb. The Nemerow comprehensive index indicated all sampling points were graded as severe pollution. The mean of total non-carcinogenic health risk values and the mean of carcinogenic health risk values for the target heavy metals in the area were higher than the threshold (1) and the maximum acceptable risk (1.0×10–4), respectively. The total carcinogenic health risks for adults and children reached 1.1×10–3 and 1.67×10–3, respectively. The mean non-carcinogenic health risk values of As, Co, Cr, and Pb pollution were greater than 1, and the maximum non-cancer risk value of Sb for children was greater than 1. The mean carcinogenic risk values of Ni, As, and Cu exceeded 1.0×10–4 for both adults and children, and the maximum carcinogenic risk values of Be and Cr for children were more than 1.0×10–4. Conclusion The farmland soil around the hugest realgar mine in Asia is contaminated by multiple metals. The study soil is seriously polluted by Cd, Se, Pb, As, Hg, Be, B, Mo, V, Ni, Cu, Pb, Zn, Co, and Ba. The pollution of Ni, As, Cu, Cr, and Be is considered as carcinogenic hazards to health, while the pollution of As, Co, Cr, Pb, and Sb poses non-carcinogenic health risks. Our study findings show that the soil is polluted by Co and Group 1 carcinogen Be, which could cause health risks; although Cr and Sb have not reached severe pollution levels, there are certain health risks and also need attention.

CircFhit Modulates GABAergic Synaptic Transmission via Regulating the Parental Gene Fhit Expression in the Spinal Dorsal Horn in a Rat Model of Neuropathic Pain / 神经科学通报·英文版

Effective treatments for neuropathic pain are lacking due to our limited understanding of the mechanisms. The circRNAs are mainly enriched in the central nervous system. However, their function in various physiological and pathological conditions have yet to be determined. Here, we identified circFhit, an exon-intron circRNA expressed in GABAergic neurons, which reduced the inhibitory synaptic transmission in the spinal dorsal horn to mediate spared nerve injury-induced neuropathic pain. Moreover, we found that circFhit decreased the expression of GAD65 and induced hyperexcitation in NK1R+ neurons by promoting the expression of its parental gene Fhit in cis. Mechanistically, circFhit was directly bound to the intronic region of Fhit, and formed a circFhit/HNRNPK complex to promote Pol II phosphorylation and H2B monoubiquitination by recruiting CDK9 and RNF40 to the Fhit intron. In summary, we revealed that the exon-intron circFhit contributes to GABAergic neuron-mediated NK1R+ neuronal hyperexcitation and neuropathic pain via regulating Fhit in cis.

Effects of chemical fertilizer reduction and organic fertilizer substitution on yield and quality of Saposhnikovia divaricata / 中国中药杂志

To explore the suitable fertilizing pattern for Saposhnikovia divaricata in the genuine producing area, a field trial was carried out to investigate the changes in the yield and quality of medicinal materials and soil in different fertilization patterns, such as organic fertilizer substitution(organic fertilizer+NPK fertilizer) and chemical fertilizer reduction(organic fertilizer+NPK fertilizer decrement and organic fertilizer+NPK fertilizer decrement+soil conditioner). The comprehensive analysis of all treatments was based on the medicine quality evaluation data set and soil quality evaluation data set, respectively, by CRITIC weight method. The results showed that(1) the yield of S. divaricate increased by 4.93%-12.67% under the organic fertilizer substitution mode, and the yield increased by 44.43% under the treatment of chemical fertilizer reduction YHT15, which was higher than that of the organic fertilizer substitution mode.(2) The quality of S. divaricate under the two fertilization modes was superior to the standard in the Chinese Pharmacopoeia, and the application of biochar was helpful to improve the quality of S. divaricate quality, with an increase of 82.83%-181.54%. CRITIC method analysis showed that fertilization treatments with high comprehensive scores were YHT15, YH30, and YH15.(3) Soil quality under the two fertilization modes was higher than that under the control. The fertilization treatments with higher comprehensive scores of soil quality were YHT15, YHT30, and YHT. The fertilization mode of adding biochar as soil conditioner, applying an appropriate amount of organic fertilizer, and reducing part of chemical fertilizer is the appropriate way to develop ecological plantation of S. divaricata in the Baicheng area in the western Jilin province. The specific fertilization mode is as follows. The basic fertilizer was 361 kg·hm~(-2) superphosphate+110 kg·hm~(-2) potassium sulfate+82 kg·hm~(-2) organic fertilizer+10 000 kg·hm~(-2) rice husk biochar, and urea was applied as top fertilizer three times, 29, 29, and 20 kg·hm~(-2), respectively.

Preparation and cellular uptake study of anemoside B4 and PD-L1 siRNA co-delivered cRGD-modified targeting liposomes / 中国药房

OBJECTIVE To prepare anemoside B4 （AB4） and programmed cell death ligand 1 （PDL1） siRNA （siP） co- delivered cRGD-modified targeting liposomes （AB4/siP-c-L）， and to study the cellular uptake in vitro. METHODS The cRGD- modified AB4-loaded targeted liposomes （AB4-c-L） were prepared by ethanol injection. AB4-c-L was mixed with 20 nmol/L siP in the same volume and AB4/siP-c-L was obtained through electrostatic adsorption. The particle size， Zeta potential， morphology， encapsulation efficiency and drug content， in vitro release behavior and serum stability of AB4/siP-c-L were investigated by laser scattering particle size tester， transmission electron microscopy， ultrafiltration centrifugation， dialysis and agar-gel electrophoresis block test. Cellular uptake of AB4/siP-c-L by Lewis lung cancer cells LLC and its intracellular localization were evaluated by flow cytometry and confocal laser scan technique. RESULTS The average particle size of AB4/siP-c-L was （187.4±3.1） nm， and the Zeta potential was （33.5±1.4） mV. AB4/siP-c-L was spheroidal in shape. The encapsulation efficiency and content of AB4 were （95.2±0.4） % and （1.0±0.2） mg/mL， respectively. AB4/siP-c-L could better package siP， and exhibited good serum stability， obvious pH sensitivity and sustained release property. The uptake rate of AB4/siP-c-L by LLC cells was significantly higher than that of free drug， and was able to accumulate in cytoplasm. CONCLUSIONS AB4/siP-c-L can effectively realize the co-loading of AB4 and gene drug siP， which has certain in vitro targeting to LLC cells.

Clinical significance of multigene assay in papillary thyroid carcinoma / 临床耳鼻咽喉头颈外科杂志

Objective:To analyze the clinical significance of multigene assay in papillary thyroid carcinoma（PTC）. Methods:Patients who underwent thyroidectomy in a tertiary hospital from August 2021 to May 2022 were enrolled. The eight-gene panel was used to detect the tumor tissue of patients, and the correlation between gene mutations and clinical features was analyzed. Results:Among 161 patients, mutation rate of BRAF V600E, RET/PTC1 and TERT promotor were 82.0%, 6.8% and 4.3%, respectively. BRAF V600E mutation was more common in male patients（P=0.023）. TERT promotor-mutated tumors had a large diameter（P=0.019）, a high proportion of multifocal lesions（P=0.050）, and a large number of lymph node metastases（P=0.031）. Among 89 patients who completed preoperative BRAF detection, there was a strong consistency between the preoperative aspiration test and postoperative panel（Cohen κ=0.694, 95%CI: 0.482-0.906, P<0.01）. In the hematoxylin-eosin sections obtained from 80 patients, BRAF V600E was still the main type of gene mutation, and the classical/follicular type was more distributed. TERT promotor and RET/PTC1 mutation were the main genetic events for tall-cell/columnar/hobnail type and diffuse sclerosing type, respectively. One-way ANOVA showed that there were differences in diagnosis age（P=0.029） and tumor size（P<0.01） among different pathological types. Conclusion:As a simple and feasible clinical detection method for PTC, the multigene assay can supplement the identification of important genetic events other than BRAF V600E, and provide more prognostic information and follow-up hints for postoperative patients.

Value of fractional flow reserve derived from coronary computed tomographic angiography and plaque quantitative analysis in predicting adverse outcomes of non-obstructive coronary heart disease / 中华危重病急救医学

OBJECTIVE@#To investigate the value of coronary computed tomographic angiography (CCTA)-based fractional flow reserve (CT-FFR) and plaque quantitative analysis in predicting adverse outcomes in patients with non-obstructive coronary heart disease (CAD).@*METHODS@#Clinical data of patients with non-obstructive CAD who underwent CCTA at the Affiliated Hospital of Jiangnan University from March 2014 to March 2018 were retrospectively analyzed and followed up, and the occurrence of major adverse cardiovascular event (MACE) was recorded. The patients were divided into MACE and non-MACE groups according to the occurrence of MACE. The clinical data, CCTA plaque characteristics including plaque length, stenosis degree, minimum lumen area, total plaque volume, non-calcified plaque volume, calcified plaque volume, plaque burden (PB) and remodelling index (RI), and CT-FFR were compared between the two groups. Multivaritate Cox proportional risk model was used to evaluate the relationship between clinical factors, CCTA parameters and MACE. The receiver operator characteristic curve (ROC curve) was used to assess the predictive power of outcome prediction model based on different CCTA parameters.@*RESULTS@#Finally 217 patients were included, of which 43 (19.8%) had MACE and 174 (80.2%) did not. The median follow-up interval was 24 (16, 30) months. The CCTA showed that patients in the MACE group had more severe stenosis than that in the non-MACE group [(44.3±3.8)% vs. (39.5±2.5)%], larger total plaque volume and non-calcified plaque volume [total plaque volume (mm3): 275.1 (197.1, 376.9), non-calcified plaque volume (mm3): 161.5 (114.5, 307.8) vs. 117.9 (77.7, 185.5)], PB and RI were larger [PB: 50.2% (42.1%, 54.8%) vs. 45.1% (38.2%, 51.7%), RI: 1.19 (0.93, 1.29) vs. 1.03 (0.90, 1.22)], CT-FFR value was lower [0.85 (0.80, 0.88) vs. 0.92 (0.87, 0.97)], and the differences were statistically significant (all P < 0.05). Cox regression analysis showed that non-calcified plaques volume [hazard ratio (HR) = 1.005. 95% confidence interval (95%CI) was 1.025-4.866], PB ≥ 50% (HR = 3.146, 95%CI was 1.443-6.906), RI ≥ 1.10 (HR = 2.223, 95%CI was 1.002-1.009) and CT-FFR ≤ 0.87 (HR = 2.615, 95%CI was 1.016-6.732) were independent predictors of MACE (all P < 0.05). The model based on CCTA stenosis degree+CT-FFR+quantitative plaque characteristics (including non-calcified plaque volume, RI, PB) [area under the ROC curve (AUC) = 0.91, 95%CI was 0.87-0.95] had significantly better predictive efficacy for adverse outcomes than the model based on CCTA stenosis degree (AUC = 0.63, 95%CI was 0.54-0.71) and the model based on CCTA stenosis degree+CT-FFR (AUC = 0.71, 95%CI was 0.63-0.79; both P < 0.01).@*CONCLUSIONS@#CT-FFR and plaque quantitative analysis based on CCTA are helpful in predicting adverse outcomes in patients with non-obstructive CAD. Non-calcified plaque volume, RI, PB and CT-FFR are important predictors of MACE. Compared with the prediction model based on stenosis degree and CT-FFR, the combined plaque quantitative index can significantly improve the prediction efficiency of adverse outcomes in patients with non-obstructive CAD.

A multicenter clinical study of the impact of COVID-19 pandemic on hospitalization of children with bronchiolitis / 国际儿科学杂志

Objective:In order to explore the impact of corona virus disease 2019(COVID-19)on the hospitalization of children with bronchiolitis and to improve clinicians′ understanding of the characteristics of bronchiolitis during the COVID-19 epidemic.Methods:This was a multicenter clinical study, and the data have been collected from 23 children′s medical centers in China.All the clinical data were retrospectively collected from children with bronchiolitis who were hospitalized at each study center from January 1, 2019 to December 31, 2021.The results included gender, age at hospitalization, length of stay, respiratory syncytial virus(RSV) test results, severity rating, ICU treatment, and the total number of children hospitalized with respiratory tract infection during the same period.The clinical data of children with bronchiolitis in 2019 before COVID-19 epidemic and in 2020、2021 during COVID-19 epidemic were statistically analyzed and compared.Results:According to a summary of data provided by 23 children′s medical centers, there were 4 909 cases of bronchiolitis in 2019, 2 654 cases in 2020, and 3 500 cases in 2021.Compared with 2019, the number of bronchiolitis cases decreased by 45.94% in 2020 and 28.70% in 2021.In 2019, 2020 and 2021, there were no significant differences in gender ratio, age, and duration of hospitalization.Compared with 2019, the ratio of bronchiolitis to the total number of hospitalizations for respiratory tract infection decreased significantly in 2020 and 2021( χ2=12.762, P<0.05; χ2=84.845, P<0.05).The proportion of moderate to severe bronchiolitis cases in both 2020 and 2021 was lower than that in 2019, and the difference was statistically significant ( χ2=4.054, P<0.05; χ2=8.109, P<0.05).There was no statistically significant difference in the proportion of bronchiolitis cases requiring ICU treatment between 2019, 2020, and 2021 ( χ2=1.914, P>0.05).In 2019, a total of 52.60%(2 582/4 909) of children with bronchiolitis underwent RSV pathogen testing, and among them, there were 708 cases with RSV positive, accounting for 28.00%.In 2020, 54.14%(1 437/2 654) of children with bronchiolitis underwent RSV pathogen testing, and there were 403 cases with RSV positive, accounting for 28.04%.In 2021, 66.80%(2 238/3 500) of children with bronchiolitis underwent RSV pathogen testing, and there were 935 cases with RSV positive, accounting for 41.78%.Compared with 2019 and 2020, the RSV positive rate in 2021 showed a significant increase( χ2=99.673, P<0.05; χ2=71.292, P<0.05). Conclusion:During the COVID-19 epidemic, the implementation of epidemic prevention and control measures reduced the hospitalization rate and severity of bronchiolitis, but did not reduce the positive rate of RSV detection.