ObjectiveSerum metabolomics of acute lung injury（ALI） in rats was conducted using ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS） to explore the similarities and differences in the mechanism of Qingqiao（harvested when the fruits of Forsythiae Fructus were initially ripe and still green in color） and Laoqiao（harvested when the fruits of Forsythiae Fructus were ripe） in the treatment of ALI. MethodA total of 24 SD male rats were acclimatized and fed for 1 week， 6 of them were randomly selected for the blank group and 18 for the experimental group. The ALI model was induced in the experimental group by tracheal intubation with lipopolysaccharide（LPS）. After successfully constructing the ALI model， these rats was randomly divided into model group， Qingqiao group and Laoqiao group， with 6 rats in each group. The Qingqiao and Laoqiao groups were administered orally once a day at a dose of 1.5 g·kg^-1， while the blank and model groups received an equivalent volume of saline for 3 consecutive days. The pathological conditions of rat lung tissues were comprehensively assessed by hematoxylin-eosin（HE） staining， wet-to-dry mass ratio（W/D） of lung tissues， and protein concentration in rat bronchoalveolar lavage fluid（BALF）. The levels of interleukin（IL）-6， IL-1β and tumor necrosis factor（TNF）-α in BALF were quantified using enzyme-linked immunosorbent assay（ELISA）. UPLC-Q-TOF-MS was used to identify and analyze the chemical compositions of Qingqiao and Laoqiao， and serum metabolomics of rats in each group was analyzed， combined with multivariate statistical analysis with variable importance in the projection（VIP） value>1， P<0.05 from t-test， and fold change（FC）≥1.5 or FC≤0.5 to screen the differential metabolites Qingqiao and Laoqiao for the treatment of ALI. The Kyoto Encyclopedia of Genes and Genomes（KEGG） database was used in combination with MetaboAnalyst for the metabolic pathway analysis of the screened differential metabolites. ResultCompared with the blank group， rats in the model group exhibited enlarged alveolar lumen， ruptured alveoli， interstitial hemorrhage， bronchial exudation of a large number of neutrophils and erythrocytes， and a significant increase in the protein concentration in the BALF and the W/D value of the lung tissues（P<0.01）. In contrast， compared with the model group， rats in the Qingqiao group and the Laoqiao group showed reduced bronchial hemorrhage in the lungs， and the protein concentration in the BALF and the W/D value of the lung tissues were significantly decreased（P<0.01）， the lung injury was significantly alleviated， but more obvious in the Qingqiao group. Compared with the blank group， the expression levels of IL-6， IL-1β and TNF-α in the BALF of the model group were significantly higher（P<0.01）. Additionally， compared with the model group， the expression levels of IL-6， IL-1β and TNF-α in the Qingqiao and Laoqiao groups were significantly lower（P<0.01）. The chemical composition analysis of Qingqiao and Laoqiao revealed that 63 components were detected in Qingqiao and 55 components were detected in Laoqiao， with 47 common components， 16 components unique to Qingqiao and 8 components unique to Laoqiao. Characterizing the differences in serum metabolomics in rats， 19 and 12 metabolites were called back by Qingqiao and Laoqiao， respectively. The metabolic pathway enrichment analysis showed that Qingqiao exerted its therapeutic effects by affecting 6 key metabolic pathways， including linoleic acid metabolism， phenylalanine metabolism， phenylalanine， tyrosine and tryptophan biosynthesis， glycerophospholipid metabolism， α-linolenic acid metabolism， and arachidonic acid metabolism， and Laoqiao exerted therapeutic effects by affecting 6 key metabolic pathways， including linoleic acid metabolism， arachidonic acid metabolism， sphingolipid metabolism， phenylalanine metabolism， ascorbate and aldarate metabolism， and glycerophospholipid metabolism. ConclusionQingqiao and Laoqiao have therapeutic effects on ALI， and Qingqiao is more effective. Both of them can play a therapeutic role in ALI by regulating amino acid metabolism and lipid metabolism， but the metabolic pathways affected by them are different.

Objective:To investigate the clinical characteristics and treatment of patients with CD4+CD8-T-cell large granular lymphocytic leukemia(T-LGLL).Methods:The clinical manifestations,diagnosis and treatment of 1 case of CD4+CD8-T-LGLL patient were reported,and relevant literatures were reviewed.Results:The patient was a 70-year-old woman with slow clinical progress,mainly manifested by thrombocytopenia and myelodysplasia.The blood smear was mainly composed of large granular lymphocytes.Immunotyping and T-cell receptor gene rearrangement analysis showed that it was in line with T-LGLL.Partial remission(PR)was achieved through the treatment of cyclophosphamide(50 mg/d)combined with prednisone(gradually reduced and stopped later).Conclusion:CD4+CD8-T-LGLL is very rare in clinical practice,and its clinical manifestations are different from those of CD4-CD8+T-LGLL.

Objective:To analyze the relationship between the systemic immune inflammation index (SII) and risk stratification of acute pulmonary embolism.Methods:The clinical data of patients with moderate to critical pulmonary embolism admitted to the emergency department of Peking University People's Hospital from January 2018 to May 2022 were respectively collected. The patients divided into a medium to high-risk group and a medium to low-risk group according to risk stratification. The SII index, simplified pulmonary embolism severity index (sPESI), general information, disease history, laboratory test results, and other indicators between two groups of patients were compared. Logistic regression was used to analyze the relationship between SII and risk stratification in patients with acute pulmonary embolism.Results:A total of 97 patients with moderate to critical pulmonary embolism were included, including 43 were in the medium high risk group and 54 were in the medium low risk group. The data of SII index, white blood cell count, C-reactive protein, and sPESI of patients in the medium to high-risk group were significantly higher than those in the medium to low-risk group (all P<0.05), and lower lymphocyte count than those in the medium to low-risk group ( P<0.05). Logistic regression analysis showed that SII ( OR=1.001, 95% CI: 1.000-1.002, P=0.027) and sPESI ( OR=2.000, 95% CI: 1.155-3.464, P=0.013) were the main factors affecting risk stratification in patients with acute pulmonary embolism. The AUC of SII, sPESI score, and their combined evaluation of acute pulmonary embolism risk stratification were 0.710, 0.625, and 0.739, respectively. The combined evaluation value of the two indicators was higher than that of a single indicator ( P=0.007). Conclusion:SII has good application value in risk stratification of acute pulmonary embolism, and the combined sPESI score has higher value.

Objective: To explore the role of mobile phone addiction and anxiety symptoms in the relationship between childhood psychological abuse and depressive symptoms among college students, in order to provide a basis for mental health promotion. Methods: From February to May 2023, a stratified random sampling method was used to select 1 799 freshmen to juniors from a university in Wuhu City, Anhui Province. The questionnaire survey was conducted using the 2-item Patient Health Questionnaire (PHQ-2), Child Psychological Maltreatment Scale (CPMS), Mobile Phone Addiction Tendency Scale (MPATS), 2-item General Anxiety Disorder (GAD-2). Correlations among each variable were analyzed, and the chain mediating effect of mobile phone addiction and anxiety symptoms was explored. Results: The detection rate of depressive symptoms among college students was 9.7%, and the positive detection rate of childhood psychological abuse was 28.6%. Depressive symptoms were positively correlated with childhood psychological abuse, mobile phone addiction and anxiety symptoms ( r =0.28, 0.32, 0.27, P <0.01). Childhood psychological abuse was positively correlated with mobile phone addiction and anxiety symptoms ( r =0.29, 0.71, P <0.01). Mobile phone addiction and anxiety symptoms were positively correlated ( r =0.30, P <0.01). Childhood psychological abuse could effectively predict depressiove symptoms, mobile phone addiction and anxiety symptoms ( β =0.08, 0.06, 0.66, P <0.01). Mobile phone addiction and anxiety symptoms had a chain mediating effect between childhood psychological abuse and depression symptoms, with a total indirect mediating effect (effect=25.27%, P <0.05), accounting for 72.44% of the total effect. Conclusions Mobile phone addiction and anxiety symptoms play a chain mediating role between childhood psychological abuse and depressive symptoms. Focusing on childhood psychological abuse, mobile phone addiction and anxiety among college students are beneficial for depression symptoms prevention.

Enterotoxigenic Escherichia coli（ETEC）infection can induce watery diarrhea，leading to dehydration，electrolyte disturbance，and even death in severe cases. Recombinant B subunit/inactivated whole-cell cholera（rBS/WC）vaccine is effective in preventing ETEC infectious diarrhea. On the basis of the latest evidence on etiology and epidemiology of ETEC，as well as the effectiveness，safety，and health economics of rBS/WC vaccine，National Clinical Research Center for Child Health（The Children’s Hospital，Zhejiang University School of Medicine）and Zhejiang Provincial Center for Disease Control and Prevention invited experts to develop expert consensus on rBS/WC vaccine in prevention of ETEC infectious diarrhea. It aims to provide the clinicians and vaccination professionals with guidelines on using rBS/WC vaccine to reduce the incidence of ETEC infectious diarrhea.

Morphine is a frequently used analgesic that activates the mu-opioid receptor(MOR),which has prominent side effects of tolerance.Although the inefficiency of morphine in inducing the endocytosis of MOR underlies the development of morphine tolerance,currently,there is no effective therapy to treat morphine tolerance.In the current study,we aimed to develop a monoclonal antibody(mAb)precisely targeting MOR and to determine its therapeutic efficacy on morphine tolerance and the underlying molecular mechanisms.We successfully prepared a mAb targeting MOR,named 3A5C7,by hybridoma technique using a strategy of deoxyribonucleic acid immunization combined with cell immunization,and identified it as an immunoglobulin G mAb with high specificity and affinity for MOR and binding ability to antigens with spatial conformation.Treatment of two cell lines,HEK293T and SH-SY5Y,with 3A5C7 enhanced morphine-induced MOR endocytosis via a G protein-coupled receptor kinase 2(GRK2)/β-arrestin2-dependent mechanism,as demonstrated by immunofluorescence staining,flow cytometry,Western blotting,coimmunoprecipitation,and small interfering ribonucleic acid(siRNA)-based knock-down.This mAb also allowed MOR recycling from cytoplasm to plasma membrane and attenuated morphine-induced phosphorylation of MOR.We established an in vitro morphine tolerance model using differentiated SH-SY5Y cells induced by retinoic acid.Western blot,enzyme-linked immunosorbent assays,and siRNA-based knockdown revealed that 3A5C7 mAb diminished hyperactivation of adenylate cyclase,the in vitro biomarker of morphine tolerance,via the GRK2/β-arrestin2 pathway.Furthermore,in vivo hotplate test demonstrated that chronic intrathecal administration of 3A5C7 significantly alle-viated morphine tolerance in mice,and withdrawal jumping test revealed that both chronic and acute 3A5C7 intrathecal administration attenuated morphine dependence.Finally,intrathecal electroporation of silencing short hairpin RNA illustrated that the in vivo anti-tolerance and anti-dependence efficacy of 3A5C7 was mediated by enhanced morphine-induced MOR endocytosis via GRK2/β-arrestin2 pathway.Collectively,our study provided a therapeutic mAb,3A5C7,targeting MOR to treat morphine tolerance,mediated by enhancing morphine-induced MOR endocytosis.The mAb 3A5C7 demonstrates promising translational value to treat clinical morphine tolerance.

Background::Pancreatic adenocarcinoma (PAAD) is an extremely lethal malignancy. Identification of the functional genes and genetic variants related to PAAD prognosis is important and challenging. Previously identified prognostic genes from several expression profile analyses were inconsistent. The regulatory genetic variants that affect PAAD prognosis were largely unknown.Methods::Firstly, a meta-analysis was performed with seven published datasets to systematically explore the candidate prognostic genes for PAAD. Next, to identify the regulatory variants for those candidate genes, expression quantitative trait loci analysis was implemented with PAAD data resources from The Cancer Genome Atlas. Then, a two-stage association study in a total of 893 PAAD patients was conducted to interrogate the regulatory variants and find the prognostic locus. Finally, a series of biochemical experiments and phenotype assays were carried out to demonstrate the biological function of variation and genes in PAAD progression process.Results::A total of 128 genes were identified associated with the PAAD prognosis in the meta-analysis. Fourteen regulatory loci in 12 of the 128 genes were discovered, among which, only rs4887783, the functional variant in the promoter of Ring Finger and WD Repeat Domain 3 ( RFWD3), presented significant association with PAAD prognosis in both stages of the population study. Dual-luciferase reporter and electrophoretic mobility shift assays demonstrated that rs4887783-G allele, which predicts the worse prognosis, enhanced the binding of transcript factor REST, thus elevating RFWD3 expression. Further phenotypic assays revealed that excess expression of RFWD3 promoted tumor cell migration without affecting their proliferation rate. RFWD3 was highly expressed in PAAD and might orchestrate the genes in the DNA repair process. Conclusions::RFWD3 and its regulatory variant are novel genetic factors for PAAD prognosis.

The incidence of papillary thyroid cancer after liver transplantation is relatively low. This article introduces the treatment and prognosis of a case of papillary thyroid cancer after liver transplantation, and discusses the occurrence and development of thyroid cancer after liver transplantation and perioperative management and the prognosis, in order to further enhance the comprehensive management of such patients, extend the survival period and improve the quality of life.

OBJECTIVE: To analyze the current status of diagnosis and management of acute appendicitis (AA) in China. METHODS: Questionnaire survey was used to retrospectively collect data of hospitalized patients with AA from 43 medical centers nationwide in 2017 (Sort by number of cases provided: Jinling Hospital of Medical School of Nanjing University, The First Affiliated Hospital of Xinjiang Medical University, Lu'an People's Hospital, Tengzhou Central People's Hospital, Dalian Central Hospital, The Affiliated Hospital of Xuzhou Medical University, Dongying People's Hospital, Jinjiang Hospital of Traditional Chinese Medicine, Huangshan Shoukang Hospital, Xuyi People's Hospital, Nanjing Jiangbei People's Hospital, Lanzhou 940th Hospital of PLA, Heze Municipal Hospital, The First College of Clinical Medical Science of China Three Gorges University, Affiliated Jiujiang Hospital of Nanchang University, The Second People's Hospital of Hefei, Affiliated Central Hospital of Shandong Zaozhuang Mining Group, The Third People's Hospital of Kunshan City, Xuzhou First People's Hospital, The 81st Group Army Hospital of PLA, Linyi Central Hospital, The General Hospital of Huainan Eastern Hospital Group, The 908th Hospital of PLA, Liyang People's Hospital, The 901th Hospital of Joint Logistic Support Force, The Third Affiliated Hospital of Chongqing Medical University, The Fourth Hospital of Jilin University, Harbin Acheng District People's Hospital, The First Affiliated Hospital of Zhengzhou University, Nanjing Luhe People's Hospital, Taixing Municipal People's Hospital, Baotou Central Hospital, The Affiliated Hospital of Nantong University, Linyi People's Hospital, The 72st Group Army Hospital of PLA, Zaozhuang Municipal Hospital, People's Hospital of Dayu County, Taixing City Hospital of Traditional Chinese Medicine, Suzhou Municipal Hospital, Beijing Guang'anmen Hospital, Langxi County Hospital of Traditional Chinese Medicine, Nanyang Central Hospital, The Affiliated People's Hospital of Inner Mongolia Medical University).The diagnosis and management of AA were analyzed through unified summary. Different centers collected and summarized their data in 2017 and sent back the questionnaires for summary. RESULTS: A total of 8 766 AA patients were enrolled from 43 medical centers, including 4 711 males (53.7%) with median age of 39 years and 958 (10.9%) patients over 65 years old. Of 8 776 patients, 5 677 cases (64.6%) received one or more imaging examinations, and the other 3 099 (35.4%) did not receive any imaging examination. A total of 1 858 (21.2%) cases received medical treatment, mainly a combination of nitroimidazoles (1 107 cases, 59.8%) doublet regimen, followed by a single-agent regimen of non-nitroimidazoles (451 cases, 24.4%), a nitroimidazole-free doublet regimen (134 cases, 7.2%), a triple regimen of combined nitroimidazoles (116 cases, 6.3%), nitroimidazole alone (39 cases, 2.1%) and nitroimidazole-free triple regimen (3 cases, 0.2%). Of the 6 908 patients (78.8%) who underwent surgery, 4 319 (62.5%) underwent laparoscopic appendectomy and 2589 (37.5%) underwent open surgery. Ratio of laparotomy was higher in those patients under 16 years old (392 cases) or over 65 years old (258 cases) [15.1%(392/2 589) and 10.0%(258/2 589), respectively, compared with 8.5%(367/4 316) and 8.0%(347/4 316) in the same age group for laparoscopic surgery, χ²=91.415, P<0.001; χ²=15.915,P<0.001]. Patients with complicated appendicitis had higher ratio of undergoing open surgery as compared to those undergoing laparoscopic surgery [26.7%(692/2 589) vs. 15.6%(672/4 316), χ²=125.726, P<0.001].The cure rates of laparoscopic and open surgery were 100.0% and 99.8%(2 585/2 589) respectively without significant difference (P=0.206). Postoperative complication rates were 4.5%(121/2 589) and 4.7%(196/4 316) respectively, and the difference was not statistically significant (χ²=0.065, P=0.799). The incidence of surgical site infection was lower (0.6% vs. 1.7%, χ²=17.315, P<0.001), and hospital stay was shorter [6(4-7) days vs. 6(5-8) days, U=4 384 348.0, P<0.001] in the laparoscopic surgery group, while hospitalization cost was higher (median 12 527 yuan vs. 9 342 yuan, U=2 586 809.0, P<0.001). CONCLUSIONS The diagnosis of acute appendicitis is still clinically based, supplemented by imaging examination. Appendectomy is still the most effective treatment at present. Laparoscopic appendectomy has become the main treatment strategy, but anti-infective drugs are also very effective.
Acute Disease ; Adolescent ; Adult ; Aged ; Anti-Bacterial Agents ; therapeutic use ; Appendectomy ; Appendicitis ; diagnosis ; therapy ; China ; Female ; Health Care Surveys ; Humans ; Laparoscopy ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome ; Young Adult

Background: The 47,XYY syndrome could result in fertility problems. However, seldom studies reported comprehensive researches on the embryonic development and pregnancy outcomes of these patients. This study aimed to evaluate the clinical outcomes of nonmosaic 47,XYY patients performed with fluorescent in situ hybridization (FISH) and preimplantation genetic diagnosis (PGD) treatment. Methods: This was a retrospective study. Between January 2012 and May 2017, 51 infertile males with nonmosaic 47,XYY syndrome underwent FISH-PGD were included in the study. According to sex chromosomal FISH results, embryos were classified as normal signal, no nuclei fixed, no signal in fixed nuclei, suspensive signal, and abnormal signal groups, respectively. The incidence of each group, the fixation rate, and hybridization rate were calculated. Embryonic development and pregnancy outcomes were also analyzed. The measurement data were analyzed with Student's t-test. The comparison of categorical data was analyzed with the Chi-square test and Fisher's exact test when expected cell count was <5. Results: The 53 PGD cycles with 433 embryos were analyzed. The fixation rate was 89.6%, while the hybridization rate was 96.4%. There were 283 embryos with two sex chromosomal signals with clear diagnosis (65.4%). The numbers of no nuclei fixed, no signal in fixed nuclei, suspensive signal, and abnormal signal groups were 45 (10.4%), 14 (3.2%), 24 (5.5%), and 67 (15.5%), respectively. Embryos with abnormal signals were abandoned. The number of good-quality embryos was 210 (57.4%), including implanted embryos on day 4/day 5 and cryopreserved. The rates of good-quality embryos in the no nuclei fixed (22.2%), no signal in fixed nuclei (28.6%), and suspensive signal groups (33.3%) were comparable (P > 0.05), and were significantly lower than the normal signal group (66.4%, P < 0.001). The clinical pregnancy rates of fresh and frozen embryos transferred cycles were 70.6% and 85.7%, respectively. Conclusions Among embryos with a clear diagnosis of sex chromosome, about one-fifth showed abnormal signals. Embryos with two sex chromosomal signals are more likely to develop into good-quality ones. The application of the PGD by FISH may help to improve the clinical outcome s.
Female ; Humans ; In Situ Hybridization, Fluorescence ; Infertility, Male ; genetics ; Male ; Pregnancy ; Preimplantation Diagnosis ; Retrospective Studies ; Sex Chromosome Disorders ; diagnosis ; genetics ; XYY Karyotype ; diagnosis ; genetics