Objective:To investigate the effects of subcutaneous immunotherapy (SCIT) on patients′ immune markers and metabolic levels in the early stage of allergen treatment, and to gain insight into the role of SCIT in regulating immune responses and metabolic levels, so as to provide reference data for the further discovery of potential biomarkers.Methods:A longitudinal study was used to include 40 subjects who underwent SCIT with dust mite allergens in the Department of Pediatrics of the First Affiliated Hospital of Guangzhou Medical University between November 2017 and February 2022, including 20 subjects each of single mite subcutaneous immunotherapy (SM-SCIT) and double mite subcutaneous immunotherapy (DM-SCIT). In this study, levels of dust mite allergen-specific antibodies and polyunsaturated fatty acid metabolism were measured before and 12 months after treatment, while pulmonary function tests were performed. The therapeutic effects of the patients were followed up by visual analogue scale (VAS), asthma control test (ACT) and total medication scores (TMS). The results were statistically analyzed using t-test and Mann-Whitney U-test. Results:After 12 months of treatment with SCIT, both groups showed a significant decrease in total VAS score (SM-SCIT: Z=-2.298, P<0.05; DM-SCIT: Z=-3.411, P<0.001); total ACT score (SM-SCIT: Z=-2.054, P<0.05; DM-SCIT: Z=-2.014, P<0.05) and total medication scores (SM-SCIT: Z=-3.799, P<0.000 1; DM-SCIT: Z=-3.474, P<0.001) were significantly higher, in addition to significantly higher MMEF75/25 values in the DM-SCIT group ( t=-2.253, P<0.05). There was no significant change in sIgE in the SM-SCIT group ( P>0.05), and the sIgG4 levels of the Der p, Der f, p 1, p 2, f 2, and p 21 fractions were significantly elevated ( Z=-2.651, -3.771, -2.949, -2.912, -2.725, -2.128, and -3.285, respectively, all P<0.05); The sIgE of Der p 2, f 2, p 7 and p 23 fractions( Z=-2.651, -3.771, -2.949, -2.912, -2.725, -2.128, -3.285, all P<0.05) and the sIgG4 levels of the Der p, Der f, p 1, p 2, f 1, f 2, p 10, p 21 and p 23 fractions ( Z=-3.808, -3.845, -3.061, -2.688, -2.464, -3.211, -2.371, -2.091, -2.427, all P<0.05) of the DM-SCIT group were significantly elevated. Metabolomics analysis showed that arachidonic acid, docosahexaenoic acid, docosapentaenoic acid, eicosapentaenoic acid, 5, 9, 12-octadecatrienoic acid, 5(S)-hydroxylated eicosatetraenoic acid, and dihomo-gamma-linolenic acid were significantly elevated at the beginning of the treatment period after SM-SCIT treatment ( Z of -2.191, -2.497, -1.988, -2.090, -2.19, -2.803, -2.073, all P<0.05); 5(S)-hydroxylated eicosatetraenoic acid showed elevated and alpha-linolenic acid, eicosadienoic acid, and eicosapentaenoic acid were significantly decreased in the DM-SCIT group after treatment ( Z=-1.988, -2.090, -2.497, -1.988, respectively, all P<0.05). Correlation analysis showed that arachidonic acid was significantly negatively correlated with changes in dust mite-specific IgG4 ( r=-0.499, P<0.05), and that alpha-linolenic acid, 5, 9, 12-octadecatrienoic acid, and eicosapentaenoic acid were positively correlated with the ΔsIgG4 of the dust mite der p 2 ( r=0.451, 0.420, 0.474, respectively; all P<0.05). Conclusion:Significant changes in allergen-specific antibody levels and polyunsaturated fatty acid metabolism levels occur during SCIT, and the two may interact and influence each other.

Objective:To investigate the effects of subcutaneous immunotherapy (SCIT) on patients′ immune markers and metabolic levels in the early stage of allergen treatment, and to gain insight into the role of SCIT in regulating immune responses and metabolic levels, so as to provide reference data for the further discovery of potential biomarkers.Methods:A longitudinal study was used to include 40 subjects who underwent SCIT with dust mite allergens in the Department of Pediatrics of the First Affiliated Hospital of Guangzhou Medical University between November 2017 and February 2022, including 20 subjects each of single mite subcutaneous immunotherapy (SM-SCIT) and double mite subcutaneous immunotherapy (DM-SCIT). In this study, levels of dust mite allergen-specific antibodies and polyunsaturated fatty acid metabolism were measured before and 12 months after treatment, while pulmonary function tests were performed. The therapeutic effects of the patients were followed up by visual analogue scale (VAS), asthma control test (ACT) and total medication scores (TMS). The results were statistically analyzed using t-test and Mann-Whitney U-test. Results:After 12 months of treatment with SCIT, both groups showed a significant decrease in total VAS score (SM-SCIT: Z=-2.298, P<0.05; DM-SCIT: Z=-3.411, P<0.001); total ACT score (SM-SCIT: Z=-2.054, P<0.05; DM-SCIT: Z=-2.014, P<0.05) and total medication scores (SM-SCIT: Z=-3.799, P<0.000 1; DM-SCIT: Z=-3.474, P<0.001) were significantly higher, in addition to significantly higher MMEF75/25 values in the DM-SCIT group ( t=-2.253, P<0.05). There was no significant change in sIgE in the SM-SCIT group ( P>0.05), and the sIgG4 levels of the Der p, Der f, p 1, p 2, f 2, and p 21 fractions were significantly elevated ( Z=-2.651, -3.771, -2.949, -2.912, -2.725, -2.128, and -3.285, respectively, all P<0.05); The sIgE of Der p 2, f 2, p 7 and p 23 fractions( Z=-2.651, -3.771, -2.949, -2.912, -2.725, -2.128, -3.285, all P<0.05) and the sIgG4 levels of the Der p, Der f, p 1, p 2, f 1, f 2, p 10, p 21 and p 23 fractions ( Z=-3.808, -3.845, -3.061, -2.688, -2.464, -3.211, -2.371, -2.091, -2.427, all P<0.05) of the DM-SCIT group were significantly elevated. Metabolomics analysis showed that arachidonic acid, docosahexaenoic acid, docosapentaenoic acid, eicosapentaenoic acid, 5, 9, 12-octadecatrienoic acid, 5(S)-hydroxylated eicosatetraenoic acid, and dihomo-gamma-linolenic acid were significantly elevated at the beginning of the treatment period after SM-SCIT treatment ( Z of -2.191, -2.497, -1.988, -2.090, -2.19, -2.803, -2.073, all P<0.05); 5(S)-hydroxylated eicosatetraenoic acid showed elevated and alpha-linolenic acid, eicosadienoic acid, and eicosapentaenoic acid were significantly decreased in the DM-SCIT group after treatment ( Z=-1.988, -2.090, -2.497, -1.988, respectively, all P<0.05). Correlation analysis showed that arachidonic acid was significantly negatively correlated with changes in dust mite-specific IgG4 ( r=-0.499, P<0.05), and that alpha-linolenic acid, 5, 9, 12-octadecatrienoic acid, and eicosapentaenoic acid were positively correlated with the ΔsIgG4 of the dust mite der p 2 ( r=0.451, 0.420, 0.474, respectively; all P<0.05). Conclusion:Significant changes in allergen-specific antibody levels and polyunsaturated fatty acid metabolism levels occur during SCIT, and the two may interact and influence each other.

AIM: To investigate the characteristics of anterior segment structure in first-degree relatives of patients with primary angle-closure glaucoma(PACG).METHODS: A total of 48 first-degree relatives of PACG patients aged 40-60 who were treated in the Affiliated Eye Hospital of Nanchang University from September 2020 to October 2022 were selected as the observation group. Additionally, 40 cases(40 eyes)of healthy individuals without glaucoma and family history of glaucoma at the same age group were collected as the control group. They were divided into younger group(40-49 years old)and elder group(50-60 years old). All subjects were examined with ultrasound biomicroscopy(UBM)and were measured using camera measure software. The parameters mainly included anterior chamber depth(ACD), anterior chamber area(ACA), anterior chamber width(ACW), anterior segment depth(ASD), angle open distance(AOD500), trabecular iris angle(TIA), trabecular iris area(TISA500), lens vault(LV), iris curve(IC), iris thickness(IT500), scleral ciliary process angle(SCPA), and iris ciliary process distance(ICPD).RESULTS: ACD, ACA, AOD500, TISA500 and TIA in the observation group were lower than those of the control group, and LV and IC were higher than those of the control group(all P<0.05). ACD, ACA, AOD500, TISA500, and TIA of the elder group were lower than those in the age-matched control group, while LV and IC were larger than those of the age-matched control group(all P<0.05). ACD, AOD500, TISA500, and TIA of the younger observation group were smaller than those of the age-matched control group, but LV and IC were significantly larger than those of the age-matched control group(all P<0.05). ACD, ACA, AOD500, TISA500 and TIA of the elder observation group were significantly lower than those of the younger observation group, and LV and IC were significantly larger than those of the younger observation group(all P<0.05). There was a difference in the distribution of ACD between the observation group and the control group(P<0.05), and the proportion of moderate to severe shallow anterior chambers was 10 times that of the control group. Correlation analysis showed that TISA500 was positively correlated with ACD and ACA, and negatively correlated with LV and IC, and TISA500 was mainly influenced by LV. IC had a positive correlation with LV and a negative correlation with ACD and ACA.CONCLUSION: First-degree relatives of PACG with normal axial length have a high risk of angle closure. The anterior segment structures of first-degree relatives of PACG are more crowded than normal individuals, and the lens forward shift may be the initial influencing factor for narrow angle.

The passing of ethical review is a necessary conditions and prerequisite for the development of life science and medical research involving humans. At present, some medical and health institutions have no or insufficient ethical review capabilities. The lack of ethical review ability has become a bottleneck restricting the development of life science and medical research involving humans. According to documents such as Opinions on Deepening the Reform of the Review and Approval System and Encouraging the Innovation of Pharmaceutical and Medical Devices, Opinions on Strengthening the Ethical Governance of Science and Technology, institutions can entrust competent institutional ethics review committees or regional ethics review committees in writing to conduct ethical review. Entrustment ethical review provides a viable solution for institutions that need to carry out life science and medical research involving humans but do not have an ethics (review) committee or the ethics (review) committee is not competent to review. To conduct the entrustment ethical review, the entrustment between the principal and the trustee is required. According to The Measures for Ethical Review of Life Sciences and Medical Research Involving Humans, if medical and health institutions and their ethical review committees do not accept the formal entrustment to provide the ethical review opinions for other institutions, the local health authorities at or above the county level will impose administrative penalties and sanctions on the relevant institutions and personnel in accordance with the law. Signing the entrustment ethical review contract, implementing legal compliance entrusted ethical review to protect the rights and interests of the trustee and the principal, and protect the research participants.

Objective: To understand the prevalence and trend of diet related behaviors among secondary school students in Shanghai, and to provide a scientific basis for developing appropriate health education strategies. Methods: Anonymous questionnaire surveys were conducted among 71 291 students selected by multi stage stratified cluster sampling method from junior high schools,senior high schools and vocational schools in Shanghai in the year of 2008,2012,2015,2017,2019. The questionnaire adopted was "Shanghai adolescent health related behavior questionnaire". Test for trend test were applied for the analysis of the prevalence of their dietary behaviors. Results: The proportion of middle school students nutritional status within the normal range in each survey year were 73.40 %, 72.60%, 68.06%, 68.73%, 67.53%, respectively, while the rate of overweight and obesity increased from 13.17% in 2008 to 23.73% in 2019. The proportion of "eating fried food" decreased significantly by year, from 12.05 % to 4.23% (male, APC=-7.94%, t =-4.33, female, APC= -9.29%, t=-7.71, P <0.05) respectively. And the proportion of "eating dessert" also decreased significantly by year, from 31.66% to 11.14% (male, APC=-8.41%, t =-6.37, female, APC=-8.67%, t=-6.96, P <0.05). In the five surveys, the percentages of healthy diet related behaviors of secondary school students were 12.81%-21.82%, no significant upward trend was observed in the whole( P >0.05). The proportion of diet-related behaviors of nutrition unbalance and easily leading to obesity decreased significantly from 35.47% to 17.00%(APC=-6.71%, t= -5.00 , P <0.05). The proportion of diet related behavior of nutrition unbalance and not easily leading to obesity increased significantly from 39.15% to 60.16%(APC=3.46%, t=6.18, P <0.05). Conclusion Overweight and obesity among secondary school students in Shanghai are increasing during the past decade, and the proportion of healthy dietary behaviors is low. The knowledge of rational diet should be publicized among these students in order to develop healthy dietary behaviors.

The characteristic genetic abnormality of neuroendocrine neoplasms (NENs), a heterogeneous group of tumors found in various organs, remains to be identified. Here, based on the analysis of the splicing variants of an oncogene Focal Adhesion Kinase (FAK) in The Cancer Genome Atlas datasets that contain 9193 patients of 33 cancer subtypes, we found that Box 6/Box 7-containing FAK variants (FAK^6/7) were observed in 7 (87.5%) of 8 pancreatic neuroendocrine carcinomas and 20 (11.76%) of 170 pancreatic ductal adenocarcinomas (PDACs). We tested FAK variants in 157 tumor samples collected from Chinese patients with pancreatic tumors, and found that FAK^6/7 was positive in 34 (75.6%) of 45 pancreatic NENs, 19 (47.5%) of 40 pancreatic solid pseudopapillary neoplasms, and 2 (2.9%) of 69 PDACs. We further tested FAK splicing variants in breast neuroendocrine carcinoma (BrNECs), and found that FAK^6/7 was positive in 14 (93.3%) of 15 BrNECs but 0 in 23 non-NEC breast cancers. We explored the underlying mechanisms and found that a splicing factor serine/arginine repetitive matrix protein 4 (SRRM4) was overexpressed in FAK^6/7-positive pancreatic tumors and breast tumors, which promoted the formation of FAK^6/7 in cells. These results suggested that FAK^6/7 could be a biomarker of NENs and represent a potential therapeutic target for these orphan diseases.
Female ; Humans ; Alternative Splicing ; Breast Neoplasms/metabolism* ; Carcinoma, Pancreatic Ductal/pathology* ; Focal Adhesion Protein-Tyrosine Kinases/therapeutic use* ; Nerve Tissue Proteins/genetics* ; Neuroendocrine Tumors/genetics* ; Oncogenes ; Pancreatic Neoplasms/metabolism*

Objective:To study the treatment efficacy and safety in using needle-grasper assisted single-port laparoscopic hepaticojejunostomy to treat choledochal cysts in children.Methods:The data of 41 patients with choledochal cysts treated at the Department of Pediatric Surgery, the First Affiliated Hospital of Xiamen University and the Second Hospital of Hebei Medical University from January 2018 to December 2021 were reviewed. There were 8 males and 33 females, aged (2.5±1.9) years. These patients were divided into the needle-grasper assisted single-port laparoscopic hepaticojejunostomy group (needle-grasper group, n=21) and the single-port laparoscopic hepaticojejunostomy group (control group, n=20). Operation time, intestinal function recovery time, gastric tube retention time, abdominal drain indwelling time, postoperative hospital stay, and perioperative complications were compared between the two groups. Results:All 21 children in the needle-grasper group underwent successful surgery without any need to convert to conventional laparoscopic or open surgery. The operation time (156.4±21.2) min was significantly shorter than the control group (218.3±28.6) min ( t=2.95, P=0.017). There were no significant differences in intestinal function recovery time, gastric tube retention time, abdominal drain indwelling time, postoperative hospital stay and perioperative complications between the two groups (all P>0.05). Parents were very satisfied with the cosmetic effect of the invisible scar after surgery. Conclusion:Needle-grasper assisted single-port laparoscopic hepaticojejunostomy was safe, reliable and the operation time was shorter than using a single-port to achieve minimally invasive and scarless surgery.

An unexpected observation among the COVID-19 pandemic is that smokers constituted only 1.4%-18.5% of hospitalized adults, calling for an urgent investigation to determine the role of smoking in SARS-CoV-2 infection. Here, we show that cigarette smoke extract (CSE) and carcinogen benzo(a)pyrene (BaP) increase ACE2 mRNA but trigger ACE2 protein catabolism. BaP induces an aryl hydrocarbon receptor (AhR)-dependent upregulation of the ubiquitin E3 ligase Skp2 for ACE2 ubiquitination. ACE2 in lung tissues of non-smokers is higher than in smokers, consistent with the findings that tobacco carcinogens downregulate ACE2 in mice. Tobacco carcinogens inhibit SARS-CoV-2 spike protein pseudovirions infection of the cells. Given that tobacco smoke accounts for 8 million deaths including 2.1 million cancer deaths annually and Skp2 is an oncoprotein, tobacco use should not be recommended and cessation plan should be prepared for smokers in COVID-19 pandemic.
Adult ; Animals ; COVID-19 ; Epithelial Cells ; Humans ; Lung ; Mice ; Pandemics ; Peptidyl-Dipeptidase A ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus ; Ubiquitin-Protein Ligases/genetics*

Objective:To investigate the transcriptional changes of host factors in human rhabdomyosarcoma cells (RD) infected with echovirus 11 (E11), and to preliminarily understand the effect of polo like kinase 1(PLK1)on E11 replication and possible molecular mechanism.Methods:Transcriptome sequencing (RNA SEQ) was used to analyze the differentially expressed genes between E11 infected RD cells group and RD cell control group. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) was used to enrich and analyze significantly differentially expressed genes. The expression situation of the representative differentially expressed genes were validated by quantitative real-time polymerase chain reaction (qRT-PCR), and the effect of PLK1 inhibition on E11 replication was preliminarily explored.Results:A total of 3 726 differentially expressed genes were identified in RD cells infected with E11, and 484 differentially expressed genes were found in the infected group (0 h, 12 h, 24 h and 48 h after infection). These differentially expressed genes were mainly enriched in the immune response, intracellular signal transduction, transcription factor activity, sequence-specific DNA binding, protein kinase activity, nuclear and membrane components, and PI3K-Akt signaling pathway. qPCR was used to verify the expression of six target genes (CXCL14, IFITM1, OAS1, SAMD9, MX1 and PLK1), which were consistent with result of RNA-Seq. The expression of CXCL14, IFITM1, OAS1, SAMD9, and MX1 were up-regulated by 1.2-104.97 times, and the expression of PLK1 was down regulated by 1-5.79 times. Inhibition of PLK1 increased E11 replication.Conclusions:Inflammatory response, PI3K-Akt, MAPK and other pathways may play an important role in the antiviral immune process of E11 infection. In addition, host factor PLK1 may play a key role in E11 infection by regulating the cell cycle.

OBJECTIVE： To systematically evaluate the efficacy and safety of TCM compound preparation for tonifying kidney and activating blood circulation， and to provide evidence-based reference for rational drug use in the clinic. METHODS： By retrieving Cochrane library， PubMed， Embase， CBM， CNKI， VIP and Wanfang database， randomized controlled trials （RCTs） about TCM compound preparation for tonifying kidney and activating blood circulation （trial group） versus calcium or non-calcium agents （control group） in the treatment of postmenopausal osteoporosis were included. After literature screening， data extraction and quality evaluation with bias risk evaluation tool and Jadad scale of Cochrane system evaluator manual 5.1.0， Meta-analysis was conducted by using Stata 12.0 software， and trial sequential analysis （TSA） was conducted by using TSA 0.9 software. RESULTS： Totally 18 RCTs were included， involving 1 408 patients. The results of Meta-analysis showed that total response rate [RR＝1.35，95％CI（1.17，1.54），P＜0.000 1] and bone density[SMD＝0.24，95％CI（0.16，0.32），P＜0.000 1] of trial group were significantly higher than those of control group； blood calcium [SMD＝－0.05，95％CI（－0.09，0.00）， P＝0.033] of trial group was significantly lower than that of control group. There was no statistical significance in the levels of urine creatinine [SMD＝－1.60，95％CI（－5.94，2.74），P＝0.470]， urinary calcium/urine creatinine ratio [SMD＝－0.05，95％CI（－0.14，0.04），P＝0.295]， urinary hydroxyproline/urine creatinine ratio [SMD＝－0.16，95％CI（－1.04，0.72），P＝0.726]， ALT [SMD＝0.51，95％CI（－3.26，4.28），P＝0.790]， AST [SMD＝0.23，95％CI（－5.22，4.77），P＝0.929]， serum alkaline phosphatase [SMD＝－0.22，95％CI（－0.68，0.25），P＝0.361]， serum phosphate [SMD＝－0.02，95％CI（－0.11，0.07），P＝0.639]， urea nitrogen [SMD＝－0.19，95％CI（－0.70，0.31），P＝0.453]， estradiol [SMD＝0.62，95％CI（－0.28，1.52），P＝0.177]， IL-6 [SMD＝－1.78，95％CI（－4.86，1.30），P＝0.258] or VAS [SMD＝0.55，95％CI（－1.03，2.13），P＝0.496] between 2 groups. No server ADR was found in 2 groups. TSA showed that there were extract evidences for total response rate of TCM compound preparation in the treatment postmenopausal osteoporosis. CONCLUSIONS： TCM compound preparation for tonifying kidney and activating blood circulation shows significant therapeutic efficacy for postmenopausal osteoporosis， and can improve serum calcium and bone density with good safety.