ObjectiveThe research focuses on developing modeling and evaluation methodologies for an animal model exhibiting spleen deficiency and dampness excess syndrome， with the aim of standardizing such animal models for future reference. MethodsBy conducting a literature search on animal models of spleen deficiency and dampness excess syndrome， relevant publications meeting inclusion and exclusion criteria will be identified based on publication date， data source， types of diseases involved， animal characteristics， modeling methods， modeling duration， macroscopic syndrome assessment indicators， macroscopic quantification indicators， laboratory testing parameters， intervention approaches， positive controls and application context. A database will be established to facilitate the extraction of this information for quantitative analysis， statistical evaluation， and visual representation. ResultsA total of 137 literature articles meeting the standards have been included in the research. The primary animal species used in animal models of spleen deficiency and dampness excess are SD rats. Modeling methods include single-factor， dual-factor composite， and triple-factor composite methods， with various models widely applied in validation of pharmacological effects and mechanistic explorations. Evaluation indices of animal models for spleen deficiency and dampness excess primarily consist of macroscopic syndrome evaluation indicators and macroscopic quantitative indicators. Laboratory testing indicators are mostly related to research areas such as fluid metabolism and gastrointestinal function. The most commonly studied herbal formulas currently include Shenling Baizhu San and Pingwei San， with natural recovery and the use of the western medicine metronidazole as the most frequently used positive controls. ConclusionThe application of animal models for spleen deficiency and dampness excess is gradually increasing， with various modeling methods already simulating the typical characteristics of this syndrome pattern. However， there are still many areas that are worth contemplating and improving. This study aims to provide reference and ideas for the standardization of symptom names in animal models of spleen deficiency and dampness excess， as well as for the improvement of model construction and evaluation systems.

Abstract Fear of missing out is an emerging type of anxiety disorder in the context of the Internet and has showed significant impacts on physical and mental health of college students. The review provides an overview on the connotation, extension, and adverse effects, as well as potential underlying mechanisms of fear of missing out in mobile social media among college students, which aims to highlight future attention, as well as prevention and intervention reference on fear of missing out in college students.

ObjectiveTo study the possible mechanism of Chaihu Shugan Powder （柴胡疏肝散， CSP） in the treatment of functional dyspepsia （FD）. MethodsTwenty-four SD rats were randomly divided into a normal group， a model group， a CSP group and a probiotic group， with six rats in each group.The tail-clamping provocation method was used in all groups except for the normal group to replicate the FD rat model. Simultaneously， the normal group and the model group were given 10 ml/（kg·d） of saline by gavage， while the CSP group and the probiotic group were given 9.6 g/（kg·d） of CSP aqueous decoction and 0.945 g/（kg·d） of probiotic aqueous solution by gavage， respectively， twice daily for four weeks. After four weeks， the gastric emptying and small intestinal propulsion rates were detected in each group of rats. Hematoxylin-eosin （HE） staining was used to observe the histopathological changes in the gastric sinusoids and duodenum of the rats. The changes in the intestinal flora were analyzed by 16s rDNA high-throughput gene sequencing， and the expressions of the duodenal zona occludin 1 （ZO-1） and Occludin were detected by immunohistochemistry and western blotting. Pearson correlation analysis was performed on intestinal flora and ZO-1 and Occludin protein expression. ResultsThe gastric antrum tissue structure was clear in all groups， and the gland structure was regular， with smooth gastric tissue mucosa and no pathological changes such as erosion and ulcer. Compared to those in the normal group， the intestinal villi in the duodenal tissue in the model group were significantly reduced or atrophied， and the goblet cells were arranged in disorder， with eosinophilic infiltration； the gastric emptying rate and small intestinal propulsion rate， as well as ZO-1 and Occludin protein expression in duodenal tissue significantly decreased （P＜0.01）. Compared to those in the model group， the duodenal tissue structure was clear， and the length intestinal villi was longer， with goblet cells neatly arranged in the CSP group and the probiotic group； no obvious eosinophil infiltration was found， and the gastric emptying rate and small intestinal propulsion rate as well as ZO-1 and Occludin protein expression significantly increased in the CSP group； a small amount of eosinophil infiltration was found， and the gastric emptying rate and Occludin protein expression significantly increased in the probiotic group （P＜0.05 or P＜0.01）. Beta diversity analysis of intestinal flora showed that the overall structure of intestinal flora in the model group changed significantly compared to that in the normal group （P＜0.01）. The overall structure of the intestinal flora in the CSP group and the probiotic group was closer to the normal group than the model group. Species composition analysis showed that the relative abundance of the Firmicutes decreased， while the relative abundance of the Bacteroidetes and norank_f_Muribaculaceae increased， and the Bacteroidetes/Firmicutes value increased in the model group than those in the normal group （P＜0.05 or P＜0.01）. Compared to those in the model group， the relative abundance of the Firmicutes increased， while the relative abundance of the Bacteroidetes and norank_f_Muribaculaceae， as well as the Bacteroidetes/Firmicutes value decreased in the CSP group and the probiotic group （P＜0.05 or P＜0.01）. There was no statistically significant difference in each indicator between the probiotic group and the CSP group （P＞0.05）. Pearson correlation analysis showed that at the phylum level， Firmicutes was positively correlated with ZO-1 （r=0.610， P=0.016） and Occludin （r=0.694， P=0.004） protein expression. Bacteroidetes was negatively correlated with ZO-1 （r=-0.557， P=0.031） and Occludin （r=-0.662， P=0.007） protein expression. At the genus level， norank_f_Muribaculaceae was negatively correlated with ZO-1 （r=-0.727， P=0.002） and Occludin （r=-0.760，P=0.001） protein expression. ConclusionCSP can restore the structure of intestinal flora， regulate the abundance levels of Firmicutes， Bacteroidetes and norank_f_Muribaculaceae， up-regulate ZO-1 and Occludin proteins， and thus repairing the duodenal mucosal barrier， and playing a therapeutic role in FD rats.

The CD19-targeting bispecific T-cell engager blinatumomab has shown remarkable efficacy in patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia. However, several studies showed that blinatumomab has a short plasma half-life due to its low molecular weight, and thus its clinical use is limited. Furthermore, multiple trials have shown that approximately 30% of blinatumomab-relapsed cases are characterized by CD19 negative leukemic cells. Here, we design and characterize two novel antibodies, A-319 and A-2019. Blinatumomab and A-319 are CD3/CD19 bispecific antibodies with different molecular sizes and structures, and A-2019 is a novel CD3/CD19/CD20 trispecific antibody with an additional anti-CD20 function. Our in vitro, ex vivo, and in vivo experiments demonstrated that A-319 and A-2019 are potent antitumor agents and capable of recruiting CD3 positive T cells, enhancing T-cell function, mediating B-cell depletion, and eventually inhibiting tumor growth in Raji xenograft models. The two molecules are complementary in terms of efficacy and specificity profile. The activity of A-319 demonstrated superior to that of A-2019, whereas A-2019 has an additional capability to target CD20 in cells missing CD19, suggesting its potential function against CD19 weak or negative CD20 positive leukemic cells.
Antigens, CD19/therapeutic use* ; Antineoplastic Agents/pharmacology* ; Humans ; Immunotherapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; T-Lymphocytes

Objective:To improve the level of clinical diagnosis and treatment by analyzing the clinical features and relevant factors of cryptococcosis neoformans in patients with connective tissue disease(CTD).Methods:Twelve patients with CTD and cryptococcosis neoformans infection in Peking University People's Hospital from January 2010 to April 2021 were retrospectively enrolled. Clinical and laboratory data, treatment and outcome were collected and analyzed. Independent sample t-test or Rank-sum test was used. Results:The age of the patients ranged from 18 to 85 years old(mean 51 years old), all of whom were female. None of them were exposed to pigeons and their feces. Of the 12 patients, 3 patients suffered from rheumatoid arthritis, 7 patients had systemic lupus erythematosus, 1 patient was diagnosed with primary Sj?gren 's syndrome, and 1 patient was diagnosed as undifferentiated connective tissue disease. Four cases were cryptococcal meningitis, 8 were pulmonary cryptococcosis. None of the 12 patients had immunodeficiency virus infection. All 12 patients were given glucocorticoid alone or combined with immunosuppressive or biological agents. All were detected with positive cryptococcus neoformans antigen in serum; 6 got lumbar puncture, 2 cases were positive for ink stain, cerebrospinal fluid (CSF) culture were positive in 2, in whom 3 had high intracranial pressure, in which the highest one was more than 600 mmH 2O (1 mmH 2O=0.009 8 kPa); 7 cases underwent lung biopsy. Among these patients, all were positive for cryptococcosis neoformans in lung tissue pathological examination; 6 had the number of peripheral lymphocytes less than 1.0×10 9/L, and 2 were detected for the number of CD4 + T cell, which was significantly decreased. As for the initial anti-fungal drug therapy, all cases were treated with fluconazole intravenously; 2 were treated with combined amphotericin, 1 was treated with combined fluorocytosine, 1 was treated with amphotericin and fluorocytosine. Then oral flu-conazole was prescribed as sequential therapy. The whole treatmentcourse ranged from 4 to 21 months. Eleven patients were cured, and 1 was relieved. Conclusion:Patients with connective tissue disease complicated with cryptococcus neoformans infection have atypical clinical symptoms. Treatment with immunosuppressive drugs and glucocorticoids are related causes. Patients with decreased peripheral blood lymphocytes, especially CD4 + T cell, are more susceptible to infection. Early diagnosis and timely treatment are the key to improve the prognosis and cure of the disease.

With the development of society and economy, the disease spectrum of Chinese residents has undergone a major change, and the public health emergencies have occasionally occurred. The new situation has put forward higher requirements on the emergency capacity, professional technical level and treatment quality of critical care treatment system. Combining with the advantages of hospital aviation, ground and Internet emergency, Henan Provincial People's Hospital established a new construction path of emergency and critical care treatment system, namely "trinity" rescue system of aviation, ground and Internet emergency treatment and the "five-ring" model of critical care treatment system in hospital. The purpose of this paper is to summarize the practical experience of the construction of emergency and critical care system in Henan Provincial People's Hospital, so as to provide reference for the management of emergency and critical care in China.

ObjectiveTo investigate the features and changing trend of drug-induced liver injury (DILI) in the elderly from 2009 to 2019, and to provide a reference for clinical prevention and treatment of DILI in the elderly. MethodsA retrospective analysis was performed for the clinical data of 2107 elderly patients, aged ≥60 years, who were diagnosed with DILI in The Fifth Medical Center of Chinese PLA General Hospital from January 2009 to December 2019, and they were divided into groups according to age. Related clinical data were analyzed, including age, sex, clinical features, prognosis, and regional distribution. The Chi-square test was used for comparison of categorical data between groups. ResultsAmong the 2107 patients with DILI, there were 802 male patients and 1305 female patients, with a male/female ratio of 1∶1.63. Cholestasis type was the most common clinical type and was observed in 1439 patients (68.3%). There was the highest number of patients in the 60-64 years group (942 patients, 44.7%), among whom 618(65.6%) were female, 589(62.5%) had cholestasis type, 471(50.0%) had chronic DILI, 421(44.7%) had drug-induced liver cirrhosis, and 25(2.7%) had drug-induced liver failure. There were 187 patients in the 75-79 years group, among whom 110 (58.8%) patients were male, 137(73.3%) had cholestasis type, 114(60.9%) had liver cirrhosis, 4(2.1%) had drug-induced liver failure. The results showed that chronic DILI was more common in the 60-64 years group, and liver cirrhosis was more common in the 75-79 years group. As for prognosis, in the 60-64 years group, 27 patients (2.9%) were cured, 885 (93.9%) were improved, 30(32%) had no response or died; in the 65-69 years group, 16 (2.8%) were cured, 528 (92.0%) were improved, and 30(5.2%) had no response or died; in the 70-74 years group, 9(2.8%) were cured, 305(94.1%) were improved, and 10 (3.6%) had no response or died. The results showed that there was no significant difference in mortality rate between the different age groups (P＞0.05). The proportion of elderly DILI patients among hospitalized DILI patients increased from 15.90% in 2009 to 22.05% in 2013 and 27.51% in 2019, with a 1.73-fold increase in 11 years. As for regional distribution, the patients in North China accounted for the highest proportion of 47.08% (the patients from Hebei, Shanxi, and Inner Mongolia accounted for 24.92%, 10.96%, and 10.25%, respectively), followed by those in Northeast China who accounted for 17.85%. The patients in Beijing accounted for 11.53%. ConclusionThe proportion of elderly DILI patients among hospitalized DILI patients tends to increase in these years. Cholestasis type is the most common clinical type, and most of the patients with this clinical type progress to chronic DILI and drug-induced liver cirrhosis. Early diagnosis, early intervention, and standardized treatment of elderly DILI should be taken seriously.

OBJECTIVE Aim to explore the value and the selection of observation target of P1 component in children with cochlear implant(CI). METHODS 13 children(4.37±0.73 years old) with right side CI and one year of regular post-CI rehabilitation were recruited as CI group. 15 gender and age (4.25±0.84)years matched children with left side external and middle ear malformation were selected as control group. We collected their AEP which showed their reaction to 1000 Hz pure tone and analyzed the P1 component. RESULTS The cut off value between CI group and control groupwas 10.4mV for P1 Amplitude(P1A) and 110.5 mV for P1 Latency(P1L). More precisely, the values of CI group were above the cut off value while the values of control group were below it. Whether choosing P1A or P1L as dividing standard, the AUC were between 0.5 and 0.9(AUC: P1A0.733, P1L0.800), which showed medium distinguishing significance. P1L component showed greater You-den index(0.590>0.471) and sensitivity(0.923> 0.538) while P1A showed greater specificity(0.933>0.667). CONCLUSION P1L shows greater ability in distinguishing the difference between CI group and control group while P1A has advantage in determining their common feature. Generally, P1L shows higher value in studying CI children. We need to make choice between P1A and P1L in different situation and use P1A and P1L standard in series or parallel.

Objective To investigate the characteristics of epidemic and genotype/subtype distribution of hepatitis C virus (HCV) among entry travelers at Tengchong port,to provide references for HCV prophylaxis and treatment.Methods A total of 54 serum samples were collected from anti-HCV positive travelers at Tengchong port from June 2009 to June 2016.HCV NS5B gene was amplified using reverse transcription polyonerase chain reation (RT-PCR) and subsequently sequenced.Based on the obtained sequences and retrieved reference sequences,phylogenetic analysis was conducted to determine HCV genotype/subtype.Results HCV infection rate among entry travelers at Tengchong ports was 0.45 ％ (54/12 059).Forty five samples were successfully genotyped.Phylogenetically,HCV genotype 3b was revealed to be the predominant subtype (28.89 ％,13/45) in this population,followed by genotype 6n (20.0％,9/45),genotype 1b (17.78％,8/45),genotype 3a (13.33％,6/45),genotype 2a (11.11％,5/45),genotype 1a (2.22％,1/45) and genotype 6a (2.22％,1/45).The major genotype in Myanmar travelers was genotype 6,while in Chinese population,genotype 1 predominated.Genotype 6 in the population showed close phylogenetic relationship with strains prevalent in China and Southeast Asia.Genotype 3 was closely clustered with strains prevalent in China.Conclusions The distribution of HCV genotypes among entry travelers at Tengchong port is impacted by HCV epidemic strains both in Yunnan province and neighboring regions.This population serves as a transmitting media which may influence the epidemiological characteristics of HCV in Tengchong and neighboring areas.

Objective To compare the value of computed tomography(CT)and magnetic resonance im-aging(MRI)in assessing the curative effect of primary liver cancer after transcatheter arterial chemoembolization (TACE). Methods 45 patients with primary hepatocellular carcinoma treated with TACE for 3 ～ 5 times were included in the research. CT ,MRI and digital subtraction angiography (DSA) were performed after treatment. DSA was used as a standard to analyze the lesions ,residual or lesion recurrence and the detection of tumor cap-sule in CT and MRI DSA. Results The scanning accuracy and sensitivity of residual lesions or lesion recurrence after TACE in CT was much lower than MRI ,and there is a significant difference between the two groups (P <0.05). In terms of tumor capsule detection accuracy after TACE ,CT was much lower than MRI(P < 0.05). In detection rate of residual or lesion recurrence in different types of lipiodol deposition after TACE ,CT was much lower than MRI (P < 0.05). Conclusions Compared with the CT test ,MRI detection has a higher accuracy and sensitivity of residual lesions or recurrence after TACE. MRI can not only effectively show the tumor cap-sule ,but also detect residual lesion or lesion recurrence of different types of lipiodol deposition. MRI is superior to CT in the evaluating the curative effect of primary liver cancer after TACE.