Objective To investigate the effect of spleen on hepatic macrophages mediated activation of hepatic stellate cells(HSCs)in mice with liver fibrosis.Methods Eighteen male C57BL/6 mice were randomly divided into three groups.Mice in Group A and Group B were injected intraperitoneally with CCl4 to establish liver fibrosis mouse model,while those in Group C were injected with corn oil as normal control.Four weeks later,mice with liver fibrosis received splenectomy(Spx)or sham operation(Sham),respectively.After continuous injection for 2 weeks,liver homogenates(L-Homo)were prepared and liver cells were isolated from the three groups.Expressions of IL-1β,IL-13,TGF-β,TNF-α,PDGF-β and VEGF in the liver homogenates of the three groups were detected by Luminex multifactor analysis.The expressions of these cytokines in liver macrophages(L-Mψ)and other non-parenchymal cells of Sham and Spx mice were analyzed by Real-time quantitative PCR(RT-qPCR)and flow cytometry.Macrophage cell line RAW264.7 or bone marrow-derived macrophages(BMDMs)were treated with liver homogenates from the Sham and Spx groups.Then the differently treated RAW264.7 cells were analyzed for mRNA expressions of cytokines and glutamine metabolism-related molecules by RT-qPCR,or transwell co-cultured with hepatic stellate cell line JS1.After co-culture,the survival and extracellular matrix expression of JS1 cells were analyzed.For comparison,Student's t test(between two groups)or one-way analysis of variance(among multiple groups)were used.Results Compared with normal control group,the concentrations of IL-1β,IL-13,TGF-β and TNF-α in the L-Homo of model group were significantly increased and showed higher levels in Sham group than in Spx group.Moreover,the hepatic macrophages were indicated as the major source of these cytokines.Consistently,macrophages treated with liver homogenate of Sham mice had increased expressions of IL-1β,TGF-β and TNF-α and glutaminase(GLS).After co-culture with macrophages treated with liver homogenate of Sham group rather than Spx group,JS1 expressed higher expressions of α-SMA and collagens.Conclusion The spleen is involved in regulating the secretion of cytokines by hepatic macrophages and enhancing their ability to activate hepatic stellate cells.

Objective:To analyze the efficacy of laparoscopic radical surgery, compared to open surgery, for incidental gallbladder cancer following cholecystectomy.Methods:Clinical data of 106 patients with incidental gallbladder cancer treated at the Second Affiliated Hospital Zhejiang University School of Medicine from April 2010 to February 2018 were retrospectively analyzed, including 66 males and 40 females, aged (64.7±7.9) years old. According to surgical approach, patients were divided into the laparoscopic group ( n=45) and open group ( n=61). Perioperative data, including intraoperative blood loss, postoperative hospital stay, and postoperative complications, were compared between the groups. Follow-ups were conducted via outpatient visits or telephone reviews. Survival analysis was performed using the Kaplan-Meier method, and the survival rates were compared using the log-rank test. Results:All 45 patients in the laparoscopic group successfully underwent the surgery without conversion to open surgery. Compared to the open group, the laparoscopic group had a reduced intraoperative blood loss [(100±25) ml vs. (200±46) ml] and a shortened postoperative hospital stay [3(2, 5) d vs. 5(4, 7) d] (both P<0.05). The postoperative complication rates were 6.7% (3/45) in the laparoscopic group and 13.1% (8/61) in the open group ( χ2=4.16, P=0.041). The cumulative survival rate after radical surgery for incidental gallbladder cancer was better in the laparoscopic group ( χ2=4.58, P=0.032). Conclusion:Compared to open surgery, laparoscopic radical surgery for incidental gallbladder cancer showed benefits in intraoperative blood loss, postoperative hospital stay, complication rates, and cumulative survival.

Ischemic stroke(IS)is a multifactorial and heterogeneous disease.Despite years of studies,effective strategies for the diagnosis,management and treatment of stroke are still lacking in clinical practice.Metabolomics is a growing field in systems biology.It is starting to show promise in the identification of biomarkers and in the use of pharmacometabolomics to help patients with certain disorders choose their course of treatment.The development of metabolomics has enabled further and more biological appli-cations.Particularly,metabolomics is increasingly being used to diagnose diseases,discover new drug targets,elucidate mechanisms,and monitor therapeutic outcomes and its potential effect on precision medicine.In this review,we reviewed some recent advances in the study of metabolomics as well as how metabolomics might be used to identify novel biomarkers and understand the mechanisms of IS.Then,the use of metabolomics approaches to investigate the molecular processes and active ingredients of Chinese herbal formulations with anti-IS capabilities is summarized.We finally summarized recent developments in single cell metabolomics for exploring the metabolic profiles of single cells.Although the field is relatively young,the development of single cell metabolomics promises to provide a powerful tool for unraveling the pathogenesis of IS.

Objective:To provide insight into the diagnosis for clinicians, the clinical characteristics, diagnosis and treatment history of 3 patients with 21-hydroxylase deficiency (21-OHD) and testicular adrenal rest tumors (TART) were analyzed.Methods:The clinical, laboratory and imaging data of 3 male patients with 21-OHD and TART, confirmed with CYP21 gene sequencing, from May 2010 to May 2021 in the First Medical Center of Chinese PLA General Hospital were analyzed retrospectively. The treatment strategy and clinical outcome were followed up.Results:All the 3 patients were first diagnosed with bilateral adrenal mass at the age of 27-42 years old. They were 145-162 cm tall. The levels of progesterone, 17-hydroxyprogesterone, and adrenocorticotropic hormone (ACTH) of the 3 patients were relatively high, and that of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) of the 3 patients were low. Testosterone level of 1 patient was significantly elevated, and that of the other 2 patients was below the lower limit of normal range. Testicular ultrasound showed heterogeneous hyperechoic masses in both testes. CT of the adrenal glands showed bilateral adrenal enlargement with mass. All 3 patients were treated with dexamethasone. After 4-96 months of follow-up, 17-hydroxyprogesterone level was kept above the median normal level. One of the patients got married and had a baby after treatment. The sizes of adrenal hyperplasia and testicular masses reduced to various degrees with the change of the testicular masses being proportional to that of adrenal hyperplasia.Conclusions:Patients with 21-OHD are prone to have TART, leading to the impaired testicular function. Early glucocorticold therapy is beneficial to the reduction of TART and restoration of testicular function.

BACKGROUND: Preliminary researches conformed that neoadjuvant immunotherapy combined with chemotherapy had a significant short-term effect in resectable non-small cell lung cancer (NSCLC), but there were few clinical trials about neoadjuvant chemoimmunotherapy in China. We aimed to assess retrospectively the antitumour activity and safety of neoadjuvant chemoimmunotherapy for resectable stage Ib-IIIb NSCLC. METHODS: Twenty patients who had been diagnosed as stage Ib-IIIb NSCLC and received chemoimmunotherapy as neoadjuvant treatment between November 2019 and December 2020, in Beijing Chest Hospital, Capital Medical University were recruited. These patients received neoadjuvant treatment for 21 days as a cycle and antitumour activity and safety were evaluated every two cycles. RESULTS: Of 20 patients received neoadjuvant chemoimmunotherapy, 17 patients underwent surgical resection. 16 patients had R0 resection (no residual tumor resection) and 1 patient had R1 resection (microscopic residual tumor resection). Radiographic objective response rate (ORR) was 85.0% (4 complete response, 13 partial response). 5.0% (1/20) of patients had stable disease, and 10.0% (2/20) of patients had progression disease. The major pathologic response (MPR) was 47.1% (8/17), and complete pathologic response (CPR) was 29.4% (5/17). 1 case developed grade IV immune-related pneumonia (IRP) and 9 (45.0%) cases had grade III hematologic toxicity. CONCLUSIONS Immunotherapy combined with chemotherapy as neoadjuvant therapy has a better efficiency and tolerable adverse effects for patients with resectable NSCLC in stage Ib-IIIb.

Objective:To explore the application effect of training methods based on cross-theoretical model in improving the master of knowledge, compliance and implementation rate of nursing students to standard prevention.Methods:A total of 92 nursing trainees participating clinical practice in Zhangjiagang Traditional Chinese Medicine Hospital and Zhangjiagang First People's Hospital in 2017 were selected as the control group, and 112 trainees were selected as the experimental group; the control group adopted conventional standard prevention training method; the training procedure of the experimental group were divided into five stages according to the behavior of trainees, and training was carried out corresponding to different stages and behavioral transformation processes. Standard prevention knowledge, compliance belief scale score, behavior change stage distribution and standard prevention implementation rate between these two groups were compared.Results:The standard prevention theory and skill assessment scores were 84.41±4.64 and 67.01±4.53 in the experimental group and the control group after intervention, respectively. The difference was statistically significant ( t value was 26.934, P<0.01). Nurse standard prevention compliance belief scale scores were 156.21±6.96 and 119.73±5.77 in the experimental group and the control group after intervention, respectively. The difference was statistically significant ( t value was 40.156, P<0.01). The distribution of behavioral changes was statistically significant ( Z value was 8.173, P<0.01). The standard prevention implementation rate of hand washing and hand disinfection, protective equipment uses, sharp and medical waste disposal, item and environmental treatment after intervention was 78.78%(438/556), 76.69%(385/502), 91.47%(193/211), 88.27%(173/196) in the experimental group, and 62.72%(254/405),62.26%(231/371), 76.22%(141/185), 69.23%(117/169) in the control group, the differences were statistically significant( x 2 values were 17.367-29.987, all P<0.01). Conclusions:The training strategy based on cross-theoretical model can improve the attention of nursing trainees to standard prevention work, change adherence beliefs, working attitudes and behaviors, and thus improve the implementation rate of standard prevention behaviors.

To investigate the clinical features, auxiliary examination and characteristics for anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis and its concomitant seizure.
 Methods: A total of 20 patients diagnosed as anti-NMDAR encephalitis were enrolled from January 2016 to September 2018 in Xiangya Hospital. The data including the clinical features, auxiliary examination, characteristics of seizure, treatment and prognosis were collected. The discharged patients were followed up for half a year.
 Results: The initial symptom in patients with anti-NMDAR encephalitis were mainly psychiatric symptom and seizure. Most of the EEG result were diffused slow waves. The mainly type of seizure in patients with anti-NMDAR encephalitis showed generalized tonic-clonic seizure. Patients occurred consciousness during the onset of the disease. MRI showed that patients with temporal lobe were more inclined to occur seizure than patients with anti-NMDAR encephalitis (P<0.05). After standardized treatment, 20 patients showed a significant improvement in modified Rankin Scale (mRS) scores and the seizure was under control within half a year. 
 Conclusion: Patients with temporal lobe affected in MRI should pay attention to the possibility of seizure occurrence. Anti-epileptic drugs and immunotherapy should be used promptly in patient with seizure. After standardized treatment, the prognosis of patients will be mostly good.
Anti-N-Methyl-D-Aspartate Receptor Encephalitis ; Humans ; Immunotherapy ; Magnetic Resonance Imaging ; Receptors, N-Methyl-D-Aspartate ; Seizures

PURPOSE: Genome-wide association studies (GWAS) have revealed that common variants on or near EDNRA, HDAC9, SOX17, RP1, CDKN2B-AS1, and RBBP8 genes are associated with intracranial aneurysm (IA) in European or Japanese populations. However, due to population heterogeneity, whether these loci are associated with IA pathogenesis in Chinese individuals is still unknown. The purpose of this study was to investigate associations among GWAS-identified loci and risk of IA in a Chinese population. MATERIALS AND METHODS: A total of 765 individuals (including 230 IA patients and 535 controls) were involved in this study. Twelve single nucleotide polymorphisms (SNPs) of candidate loci were genotyped using the Sequenom MassARRAY platform. Associations were analyzed using univariate or multivariate logistic regression analysis. RESULTS: SNPs in CDKN2B-AS1 (especially rs10757272) showed significant associations with IA in dominant and additive models [odds ratio (OR), 2.99 and 1.43; 95% confidence interval (CI), 1.44–6.24 and 1.10–1.86, respectively]. A SNP near HDAC9 (rs10230207) was associated with IA in the dominant model (OR, 1.42; 95% CI, 1.01–1.99). One SNP near RP1 (rs1072737) showed a protective effect on IA in the dominant model (OR, 0.66; 95% CI, 0.46–0.95), while another SNP in RP1 (rs9298506) showed a risk effect on IA in a recessive model (OR, 3.82; 95% CI, 1.84–7.91). No associations were observed among common variants near EDNRA, SOX17, or RBBP8 and IA. CONCLUSION: These data partially confirmed earlier results and showed that variants in CDKN2B-AS1, RP1, and HDAC9 could be genetic susceptibility factors for IA in a Chinese population.
Asian Continental Ancestry Group ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Intracranial Aneurysm ; Logistic Models ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Population Characteristics

OBJECTIVE:To provide reference for quality evaluation of Ejiao. METHODS:The contents of 17 amino acids in 18 batches of Ejiao from 18 manufacturers were analyzed by automatic amino acid analyzer;the content data was processed by prin-cipal component analysis (PCA) and hierarchical clustering analysis (HCA),in order to understand the relationship among these amino acids and categorize the Ejiao products. RESULTS:Except for a batch of Ejiao,the other 17 batches contained 17 various amino acids,including 7 necessary amino acids(Thr,Val,Met,Ile,Leu,Phe and Lys)for human being,especially the contents of Gly and Pro were higher. The total content of amino acids was arranged from 66.1% to 82.0%,showing great difference. Four main components were extracted by PCA,the cumulative contribution of which was 89.578%,and accordingly it may be consid-ered that Pro,Ala,Glu,Asp,Leu,Ile and Thr were characteristic amino acids of Ejiao products. In hierarchical clustering analy-sis,3 tree figures of commercial Ejiao product were achieved and Euclidean distance was varied among 0-25. CONCLUSIONS:There is great difference in total control of amino acid in commercial Ejiao product;Ejiao products from various manufacturers dif-fer in their amino acid contents. Ejiao is rich in collagen,and therefore,using amino acid determination would be helpful to moni-tor its quality.

In order to determine the relationship between P16 and the tumorigenesis of malignant lymphoma，silver-stained PCR-SSCP analysis and direct sequencing were used to evaluate the alterations of P16 gene in 8 human malignant lymphoma cell lines. A homolygous loss was found in SU-DHL-9 while mutations of P16 exon 2 in SU-DHL-1 and Daudi. Sequencing of the PCR-product showed three point mutations in SU-DHL-1，which were GAC to AAC in codon 72，GOT to ACT in codon 77，and a insertion of C between codon 82 and 83，respectively. This study suggested the mutations of P16 gene are highly frequent in B-cell lymphoma cell lines and may play an important role in its tumorigenesis.