Background::Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.Methods::This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied.Results::At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs. placebo, 95% CI 31%–69%) and 45% (low vs. placebo, 95% CI 26%–64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator’s Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310. Conclusion::CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.Trial Registration::ClinicalTrials.gov, NCT04805411.

Objective This study investigated the epidemic characteristics and spatio-temporal dynamics of hemorrhagic fever with renal syndrome (HFRS) in Qingdao City,China. Methods Information was collected on HFRS cases in Qingdao City from 2010 to 2022. Descriptive epidemiologic,seasonal decomposition,spatial autocorrelation,and spatio-temporal cluster analyses were performed. Results A total of 2,220 patients with HFRS were reported over the study period,with an average annual incidence of 1.89/100,000 and a case fatality rate of 2.52％. The male:female ratio was 2.8:1. 75.3％ of patients were aged between 16 and 60 years old,75.3％ of patients were farmers,and 11.6％ had both "three red" and "three pain" symptoms. The HFRS epidemic showed two-peak seasonality:the primary fall-winter peak and the minor spring peak. The HFRS epidemic presented highly spatially heterogeneous,street/township-level hot spots that were mostly distributed in Huangdao,Pingdu,and Jiaozhou. The spatio-temporal cluster analysis revealed three cluster areas in Qingdao City that were located in the south of Huangdao District during the fall-winter peak. Conclusion The distribution of HFRS in Qingdao exhibited periodic,seasonal,and regional characteristics,with high spatial clustering heterogeneity. The typical symptoms of "three red" and"three pain" in patients with HFRS were not obvious.

With wide applications of radiation therapy in the treatment of cancer and other diseases and amid the in-creasing concerns about global nuclear safety,the research and development of drugs against radiation damage has become a hot spot.Thanks to its high energy properties,ionizing radiation can not only directly damage cell DNA through targeted effects,but also indirectly affect the cell environment through non-targeted effects,leading to cell dysfunction and even death.In this paper,the mechanism of ionizing radiation damage was analyzed,and the mechanisms of action and clinical applications of four types of anti-radiation drugs,namely,antioxidant,apoptosis inhibitor,cytokine and natural radiation protection agent were discussed.These drugs have huge implications for alleviating the targeted and non-targeted effects caused by ionizing radiation.

Objective To isolate E.scherichia coli-specific bacteriophages from hospital waste water,analyze their biological character-istics and detect their cleavage effects on bacterial biofilms.Methods The phages were isolated and purified by double-layer agar plate method and their morphology was observed by transmission electron microscopy.Their one-step growth curve,in vitro lysis curve,tem-perature and acid-base stability were determined.Whole genome sequencing was used to analyze the genome composition and character-istics of bacteriophages.The crystal violet staining was used to evaluate the scavenging effects of phage on host biofilms.Results A novel Escherichia coli-specific bacteriophage named vB_EcoP-R1 was isolated from hospital sewage.Transmission electron microscopy revealed that the morphology of vB_EcoP-R1 was similar to that of Podoviridae,a member of Caudovirales,and it could survive stably in the temperature range of-20 ℃ to 50 ℃ and pH 5.0 to 11.0.The total length of the vB_EcoP-R1 genome was 40 875 bp and the GC content was 49.94％.There were no virulence genes and drug resistance genes in the phage genome.vB_EcoP-R1 was capable of lysing clinically isolated Escherichia coli and showed high species and genus specificity.After the phage acted on the host bacteria preformed biofilm for 4 h,the clearance rate of the biofilm reached 80.16％.Conclusion vB_EcoP-R1 should be a novel Escherichia coli-specif-ic bacteriophage with strong lysis and high specificity for species and genus.The bacteriophage could lyse the biofilm formed by the host bacteria,and is expected to be used as an alternative treatment for Escherichia coli infection.

Objective To investigate the status quo and its influencing factors of nurses'organizational silence in 3 Grade A general hospitals.Methods Convenient sampling method was used to investigate clinical nurses in 3 Grade A general hospitals in Xi'an from April to August 2023 by general data questionnaire,nurses'organizational silence questionnaire and hospital magnetic factor scale.Multiple linear regression was used to analyze the influencing factors of organizational silence.Results A total of 855 nurses completed the study.The total silence score of nurses was(56.33±8.55);The total score of hospital magnetic level was(107.63±12.85).There was a negative correlation between nurse tissue silence and hospital magnetic level(r=-0.318,P<0.01).Hospital magnetic level,age,job title and working time were the influential factors of nurses'organizational silence(all P<0.001),which together explained 62.60%of the variation.Conclusions The silence of nurses'tissue and the level of hospital magnetism are in the low-medium level.Nurses are younger in age,lower in professional title,shorter in nursing age and lower in hospital magnetism level,the higher the tissue age level is,the nursing managers can reduce the tissue silence of nurses by improving the hospital magnetism level.

Objective To investigate the clinical manifestations, imaging features, treatment, and prognosis of autoimmune encephalitis （AE） with positive leucine-rich glioma-inactivated 1 （LGI1） antibody. Methods A retrospective analysis was performed for the clinical data of 11 patients with LGI1 antibody-positive AE who were admitted to Department of Neurology, The Sixth Medical Center of PLA General Hospital, from 2018 to 2022. Results Among these 11 patients, there were 10 patients with epilepsy, 8 patients with cognitive impairment, 6 patients with mental and behavioral disorders, 5 patients with sleep disorders, 1 patient with speech and language impairment, 1 patient with involuntary limb movements, 1 patient with dizziness, and 7 patients with hyponatremia. All 11 patients tested positive for LGI1 antibody, and 8 patients tested positive in serum and cerebrospinal fluid; 1 patient was also positive for contactin-associated protein-like 2 antibody, and 3 patients were positive for a single antibody in serum. Lung CT showed that 1 patient had space-occupying lesion, cranial magnetic resonance imaging showed abnormalities in 6 patients, and positron emission tomography/computed tomography showed abnormalities in 3 patients. There were 7 patients with electroencephalographic abnormalities. All 11 patients had improvements in symptoms after immunotherapy. Five patients were followed up, and 6 were lost to follow-up. Conclusion The main manifestations of LGI antibody encephalitis include seizure, faciobrachial dystonic seizures, cognitive impairment, and mental and behavioral disorders accompanied by hyponatremia. The titer of LGI1 antibody in serum is more sensitive than that in cerebrospinal fluid, and a few patients may have multiple positive autoantibodies. Immunotherapy is an effective treatment method for LGI1 antibody-positive AE.

OBJECTIVE To explore the difference in chemical components of essential oil from medicinal part （rhizome）and non-medicinal parts （fibrous roots ，stems，and leaves ）of Atractylodes chinensis，and to preliminarily evaluate their antibacterial activity in vitro . METHODS The essential oil was extracted from three parts of A. chinensis by steam distillation ，and their chemical components and relative contents were analyzed and identified by gas chromatography -mass spectrometry （GC-MS）. The antibacterial activities of essential oil （5 mg/mL） from different parts against Staphylococcus aureus ，S. albus and Bacillus subtilis were determined by paper diffusion method . The correlation between chemical components in essential oil and antibacterial activity was analyzed . RESULTS A total of 60 chemical constituents were identified from the essential oilof rhizome ，fibrous roots ，stems and leaves of A. chinensis， mainly composed of terpenes ，sesquiterpenoids，alcohols and ketones. There were 8 kinds of common components in the essential oil of rhizome ，fibrous root and stem and leaves ，which were elementol ，cadinene，agarospirol，valencian citrine ， caryophyllin，β-sesquidiene，γ-eucalyptol and β-eucalyptol. A total of 26 components were identified from the essential oil of rhizome，of which the relative content of 4-benzaldehyde was the highest （31.56%）；a total of 21 components were identified from the essential oil of fibrous roots ，among which the relative content of β-eucalyptol was the highest （44.39%）；a total of 42 components were identified from the essential oil of stems and leaves ，among which the relative content of β-sesquidiene was the highest（14.83%）. The essential oil from different parts had certain antibacterial effect on S. aureus，S. albus and B. subtilis. The order of antibacterial effect was rhizome ＞fibrous roots ＞stem and leaves ；the relative contents of β-caryophyllene，α-humulene and modhephene were positively correlated with inhibitory effects of essential oil against S. aureus and B. subtilis（P＜0.05 or P＜0.01）. The relative contents of atractylone ，zingiberene and agarospirol were positively correlated with the inhibitory effect of essential oil against B. subtilis（P＜0.05 or P＜0.01）. CONCLUSIONS There are significant differences in the chemical composition and contents of essential oil from medicinal and non -medicinal parts of A. chinensis，and all of them have antibacterial activity in vitro .

To report a typical case of Morvan syndrome with positive anti-leucine rich glioma-inactivated 1(LGI1) and contactin-associated protein 2 (CASPR2) antibodies in serum and cerebrospinal fluid. A 39-years-old female initially presented weakness of extremeties. The main symptoms included paroxysmal limb pain, wheezing, itching, muscle twitching, epilepsy, hypomnesia, dysphoria, apathy, intractable insomnia, salivation and sweating. Tests of electrolytes found hypokalemia (2.7-3.1 mmol/L) and hyponatremia (130-136 mmol/L). Arterial blood gas analysis showed hypoxemia (oxygen saturation 50%-70%). Total thyroxine (TT4) was elevated to 207 nmol/L with positive thyroid peroxidase antibody (TPO-Ab) and thyroglobulin antibody (TG-Ab). LGI1and CASPR2 antibodies (CBA method) were positive in both serum and cerebrospinal fluid, and the remaining antibodies related to autoimmune encephalitis and paraneoplastic syndrome were negative. Head MRI was almost normal, while mild abnormalities were found in electroencephalogram. Electromyography showed slightly increased voltage of left quadriceps motor unit potential. After treated with corticosteroids, IVIG and mycophenolate mofetil, the patient completely improved. Cognitive function scores recovered from MoCA/MMSE (16/24) to MoCA/MMSE (26/29). Positivity of LGI1/CASPR2 antibodies both in serum/cerebrospinal fluid are rarely seen in patients with Morvan syndrome. Steroids and immunosuppressants are suggested for treatment as early as possible.

ObjectiveTo investigate the role of hepatic stellate cell (HSC) inflammation in the pathogenesis of acute-on-chronic liver failure (ACLF). MethodsA total of 45 male Kunming mice were randomly divided into control group, model group, and N-acetylcysteine (NAC) group. The mice in the model group and the NAC group were given injection of human serum albumin to establish a model of chronic liver disease, followed by intraperitoneal injection of the endotoxins lipopolysaccharide (LPS) and D-galactosamine (D-GlaN) to induce ACLF, and those in the control group were given injection of an equal volume of normal saline; the mice in the NAC group were given NAC since 1 week before the induction of NAC. The mice in the model group and the NAC group were sacrificed at 48 hours after the injection of LPS and D-GlaN. ELISA was used to measure the serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in liver tissue; HE staining was used to determine liver pathological score; ELISA was used to measure the serum levels of LPS and interleukin-1β (IL-1β). LX2 cells were stimulated by LPS and H2O2 with the presence or absence of NAC, and ELISA was used to measure the levels of IL-1β and interleukin-6 (IL-6) in medium. LX2 cells were stimulated by LPS and H2O2, and then HL7702 cells were cultured with LX2 medium; Western blot was used to measure the expression of caspase-3 and caspase-8 in HL7702 cells, and flow cytometry was used to measure the apoptosis of HL7702 cells. A one-way analysis of variance was used for comparison of continuous data between multiple groups; the least significant difference t-test was used for comparison of data with homogeneity of variance between two groups, and the Tamhane’s T2 test was used for comparison of data with heterogeneity of variance. The Kaplan-Meier survival analysis was used to evaluate survival time, and the log-rank test was used for comparison. ResultsAt 48 hours, all mice in control group survived, while 3 mice in the model group and 8 mice in the NAC group survived, suggesting that the NAC group had a better survival rate of mice than the model group (P＜0.001). Compared with the control group and the NAC group, the model group had significant increases in the serum levels of AST and ALT and the level of MDA in liver tissue, as well as a significant reduction in the level of SOD in liver tissue (all P＜0.01). The model group had a significantly higher liver pathological score than the control group and the NAC group (both P＜0.05). Both LPS and H2O2 promoted the secretion of IL-1β and IL-6 in LX2 cells, and NAC effectively inhibited the pro-inflammatory effect of H2O2 and LPS (all P＜0.05). H2O2 and LPS acted on LX2 cells and promoted the apoptosis of HL7702 cells (all P＜0.05). ConclusionLPS can promote HSC inflammation via reactive oxygen species and participates in the progression of liver failure by inducing hepatocyte apoptosis.

Objective:To explore the effect of iron overload on the cognitive function of rats and its possible internal mechanism.Methods:Thirty 8-week-old male Sprague Dawley rats of SPF degree were randomly divided into 2 groups, iron overload group(IO group) and control group(Sham group), with 15 in each group.The rats in IO group were injected intraperitoneally iron dextran(100 mg/(kg·d)) for 28 days.The cognitive function of rats was detected by Morris water maze method. Western blot method was used to detect the expression of TfR1 and autophagy-related protein p-AMPK, LC3 and Beclin1 in the hippocampus of rats. Immunofluorescence was used to observe the expression of LC3 and Beclin1 in the hippocampus of rats. HE staining was used to observe the morphological changes of neurons in the hippocampus. Transmission electron microscopy was used to observe the number of autophagosomes and the morphology of endoplasmic reticulum in hippocampus.The software of SPSS 20.0 was used for repeated measurement ANOVA and t-test. Results:Morris water maze test showed that there were significant interaction between the group factor and training time factor of escape latency( F=3.55, P<0.01). And the simple effect analysis showed that compared with the Sham group((28.09±18.41)s, (21.42±15.53)s, (16.96±8.35)s, (10.24±3.75)s), the average escape latency of rats(2nd-5th day) in IO group((56.68±30.65)s, (58.21±36.09)s, (36.58±13.54)s, (27.29±14.30)s )were significantly longer ( t=8.57, 6.81, 9.51, 7.12, P<0.01). The platform was removed on 6th day of the space exploration experiment, compared with the Sham group ((41.89±3.89)%), the percentage of time spent in the target quadrant of IO group ((25.46±3.56)%) was significantly decreased( t=24.06, P<0.01). Western blot showed that the relative expression levels of (TfR1 (2.10±0.48), p-AMPK (0.74±0.10), LC3 (1.11±0.40), Beclin1 (1.05±0.20)) in IO group in the hippocampus of the rats were significantly higher than those of the Sham group(TfR1(0.11±0.18), p-AMPK(0.19±0.02), LC3(0.22±0.11), Beclin1(0.17±0.02))( t=1.58, 14.58, 10.06, 20.65, P<0.01)). HE staining showed that compared with the Sham group, the neuron in the hippocampus of the IO group were sparsely arranged, morphologically irregular, and the number of the neurons was significantly reduced. Transmission electron microscopy showed that compared with the Sham group, the number of autophagosomes in the hippocampus of IO group was increased. Conclusion:Iron overload may exert its neurotoxic effect by increasing the level of autophagy in the hippocampus, causing cognitive dysfunction.