ObjectiveTo analyze the expression level of triggering receptor expressed on myeloid cells-1 （TREM-1） in serum and ascites of patients with cirrhotic ascites， and to investigate its correlation with clinical features and inflammatory markers and its role in the diagnosis of infection and prognostic evaluation. MethodsA total of 110 patients with cirrhotic ascites who were hospitalized in The Fifth Hospital of Shijiazhuang from January 2019 to December 2020 were enrolled， and according to the presence or absence of intra-abdominal infection， they were divided into infection group with 72 patients and non-infection group with 38 patients. The patients with infection were further divided into improvement group with 38 patients and non-improvement group with 34 patients. Clinical data and laboratory markers were collected from all patients. Serum and ascites samples were collected， and ELISA was used to measure the level of TREM-1. The independent-samples t test was used for comparison of normally distributed continuous data between two groups； the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups， and the Kruskal-Wallis H test was used for comparison between multiple groups； the chi-square test was used for comparison of categorical data between two groups. A Spearman correlation analysis was used to investigate the correlation between indicators. A multivariate Logistic regression analysis was used to identify the influencing factors for the prognosis of patients with cirrhotic ascites and infection. The receiver operating characteristic （ROC） curve was used to evaluate the diagnostic and prognostic efficacy of each indicator， and the Delong test was used for comparison of the area under the ROC curve （AUC）. ResultsThe level of TREM-1 in ascites was significantly positively correlated with that in serum （r=0.50， P<0.001）. Compared with the improvement group， the non-improvement group had a significantly higher level of TREM-1 in ascites （Z=-2.391， P=0.017） and serum （Z=-2.544， P=0.011）， and compared with the non-infection group， the infection group had a significantly higher level of TREM-1 in ascites （Z=-3.420， P<0.001）， while there was no significant difference in the level of TREM-1 in serum between the two groups （P>0.05）. The level of TREM-1 in serum and ascites were significantly positively correlated with C-reactive protein （CRP）， procalcitonin （PCT）， white blood cell count， and neutrophil-lymphocyte ratio （r=0.288， 0.344， 0.530， 0.510， 0.534， 0.454， 0.330， and 0.404， all P<0.05）. The ROC curve analysis showed that when PCT， CRP， and serum or ascitic TREM-1 were used in combination for the diagnosis of cirrhotic ascites with infection， the AUCs were 0.715 and 0.740， respectively. The multivariate Logistic regression analysis showed that CRP （odds ratio ［OR］=1.019， 95% confidence interval ［CI］： 1.001‍ ‍—‍ ‍1.038， P=0.043） and serum TREM-1 （OR=1.002， 95%CI： 1.000‍ ‍—‍ ‍1.003， P=0.016） were independent risk factors for the prognosis of patients with cirrhotic ascites and infection， and the combination of these two indicators had an AUC of 0.728 in predicting poor prognosis. ConclusionThe level of TREM-1 is closely associated with the severity of infection and prognosis in patients with cirrhotic ascites， and combined measurement of TREM-1 and CRP/PCT can improve the diagnostic accuracy of infection and provide support for prognostic evaluation.

OBJECTIVE: Based on metabonomics technology of high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) and hydrogen nuclear magnetic resonance spectroscopy (¹H NMR), the pharmacokinetic characteristics and therapeutic mechanism of Rhei Radix et Rhizoma (RhRR, Dahuang in Chinese), Eupolyphaga Steleophaga (EuS, Tubiechong in Chinese) combined with RhRR acting on acute liver injury were explored. METHODS: Models of acute liver injury were established, and the pharmacokinetic methods of five components of RhRR-EuS in rats were found by HPLC-MS/MS. The liver tissues of different groups of mice were analyzed by ¹H NMR spectroscopy combined with multivariate statistical analysis to investigate the metabolomics of RhRR-EuS and RhRR. RESULTS: Pharmacokinetic results showed there were different levels of bimodal phenomenon in different groups, and the absorption of free anthraquinone in RhRR increased after compatibility with EuS. In addition, the pathological state of acute liver injury in rats can selectively promote the absorption of emodin, chrysophanol, physcion and aloe emodin. Through 15 differential metabolites in the liver tissue of acute liver injury mice, it was revealed that RhRR-EuS and RhRR could protect the liver injury by regulating the metabolism of glutamine and glutamic acid, alanine, aspartic acid and glutamic acid, and phosphoinositide. However, the regulation of RhRR was weaker than that of RhRR-EuS. CONCLUSION For the first time, we studied the pharmacokinetics and metabolomics differences of RhRR-EuS and RhRR in rats and mice with acute liver injury, in order to provide theoretical reference for clinical treatment of liver disease by DHZCP.

Objective:To detect and analyze the α-galactosidase A ( GLA) gene mutations in Fabry disease patients and their family members, observe the clinical phenotype of the patients, and assess the therapeutic effect of agalsidase alpha. Methods:It was a case series analysis. A total of 5 Fabry disease patients was diagnosed at the First Affiliated Hospital of Sun Yat-sen University from March 2022 to April 2023, and the clinical data and blood samples of the patients and their family members were collected. Genetic testing was performed using whole exome sequencing. GLA activity and substrate concentration were measured using the liquid chromatography-tandem mass spectrometry. Patients' clinical manifestations, family history, and auxiliary examination results were collected, and the therapeutic efficacy of agalsidase alpha and disease progression were followed up.Results:A total of 5 GLA gene mutations were identified by gene sequencing, including 1 novel mutation. Among them, 4 mutations were missense mutation, and the other one was nonsense mutation. Common clinical manifestations included edema (4/5) and reduced sweating (4/5). Renal pathology biopsy of 4 patients showed varying degrees of kidney damage, one of which was combined with IgA nephropathy. Auxiliary examinations revealed ocular involvement in 4 patients, cardiac involvement in 4 patients, and hearing impairment in 2 patients. All 5 patients received agalsidase alpha treatment, with 4 male patients receiving (16.8±5.9) times administrations of agalsidase alpha, and their globotriaosylsphingosine (Lyso-GL-3) levels decreased by 45.6%±15.5% from baseline. Conclusions:One novel GLA gene mutation is detected, which enriches the human gene mutation database. Fabry disease can be accompanied by kidney disease such as IgA nephropathy. When patients present with unexplained proteinuria combined with extrarenal manifestations such as reduced sweating, Fabry disease should be considered. Agalsidase alpha treatment can reduce Lyso-GL-3 concentration, and improve clinical symptoms.

Objective:To investigate the effectiveness of nasal endoscopic anterior lacrimal recess approach combined with temporary fenestration of the nasal septum in resecting recurrent nasal inverted papilloma. Methods:Patients with recurrent nasal inverted papilloma who underwent reoperation in our hospital during the past 2 years were included . The nasal septum may hinder full access to and effective treatment of the lesions at the anterior and medial wall of the maxillary sinus by endoscope, aspirator and surgical instrument in the narrow aperture of the prelacrimal recess, although these lesions could be observed by 70° nasal endoscope. Results:The nasal septum is temporarily opened on the basis of the prelacrimal recess approach, and the nasal endoscope and instrument was introduced through trans-septal window, so as to provide a better view of the operative field and the angular range of the instrument's movement. Conclusion:The recurrent nasal inverted papilloma could be successfully managed by re-endoscopic anterior lacrimal recess approach combined with temporary fenestration of the nasal septum, and no recurrence was observed during the 2-year follow-up. This surgical approach is recommended for the inverted papilla which originates from the anterior medial wall of the maxillary sinus, as the tumor can be removed completely using this surgical approach.
Humans ; Papilloma, Inverted/pathology* ; Endoscopy ; Maxillary Sinus/pathology* ; Lacrimal Apparatus/surgery* ; Treatment Outcome ; Retrospective Studies

Objective:To investigate the association between oxygen saturation (SpO 2) and risk of 3-year all-cause mortality among Chinese older adults aged 65 or over. Methods:The participants were enrolled from Healthy Aging and Biomarkers Cohort Study in year of 2012 to 2014 in 9 longevity areas in China. In this prospective cohort study, 2 287 participants aged 65 or over were enrolled. Data on SpO 2 and body measurements were collected at baseline in 2012, and data on survival outcome and time of mortality were collected at the follow-up in 2014. Participants were divided into two groups according to whether SpO 2 was abnormal (SpO 2<94% was defined as abnormal). Results:The 2 287 participants were (86.5±12.2) years old, 1 006 were males (44.0%), and 315 (13.8%) were abnormal in SpO 2. During follow-up in 2014, 452 were died, 1 434 were survived, and 401 were lost to follow-up. The all-cause mortality rate was 19.8%, and the follow-up rate was 82.5%. The mortality rate of SpO 2 in normal group was 21.1%, and that of abnormal group was 41.6% ( P<0.001). After adjusting for confounding factors, compared to participants with normal SpO 2, participants with abnormal SpO 2 had increased risk of all-cause mortality with HR (95% CI) of 1.62 (1.31-2.02); HR (95 % CI) was 1.49 (0.98-2.26) for males and 1.71 (1.30-2.26) for females in abnormal SpO 2group, respectively; HR (95% CI) was 2.70 (0.98-7.44) for aged 65-79 years old, 1.22 (0.63-2.38) for aged 80-89 years old, and 1.72 (1.35-2.19) for aged over 90 years old in abnormal SpO 2 group, respectively. Conclusion:Abnormal SpO 2 was responsible for increased risk of 3-year all-cause mortality among Chinese elderly adults.

Objective:To investigate the association between oxygen saturation (SpO 2) and risk of 3-year all-cause mortality among Chinese older adults aged 65 or over. Methods:The participants were enrolled from Healthy Aging and Biomarkers Cohort Study in year of 2012 to 2014 in 9 longevity areas in China. In this prospective cohort study, 2 287 participants aged 65 or over were enrolled. Data on SpO 2 and body measurements were collected at baseline in 2012, and data on survival outcome and time of mortality were collected at the follow-up in 2014. Participants were divided into two groups according to whether SpO 2 was abnormal (SpO 2<94% was defined as abnormal). Results:The 2 287 participants were (86.5±12.2) years old, 1 006 were males (44.0%), and 315 (13.8%) were abnormal in SpO 2. During follow-up in 2014, 452 were died, 1 434 were survived, and 401 were lost to follow-up. The all-cause mortality rate was 19.8%, and the follow-up rate was 82.5%. The mortality rate of SpO 2 in normal group was 21.1%, and that of abnormal group was 41.6% ( P<0.001). After adjusting for confounding factors, compared to participants with normal SpO 2, participants with abnormal SpO 2 had increased risk of all-cause mortality with HR (95% CI) of 1.62 (1.31-2.02); HR (95 % CI) was 1.49 (0.98-2.26) for males and 1.71 (1.30-2.26) for females in abnormal SpO 2group, respectively; HR (95% CI) was 2.70 (0.98-7.44) for aged 65-79 years old, 1.22 (0.63-2.38) for aged 80-89 years old, and 1.72 (1.35-2.19) for aged over 90 years old in abnormal SpO 2 group, respectively. Conclusion:Abnormal SpO 2 was responsible for increased risk of 3-year all-cause mortality among Chinese elderly adults.

Objective: To investigate the association between estimated glomerular filtration rate (eGFR) and all-cause mortality in the elderly aged 65 years and older in longevity areas in China. Methods: Data used in this study were obtained from Healthy Aging and Biomarkers Cohort Study, a sub-cohort of the Chinese Longitudinal Healthy Longevity Survey, 1 802 elderly adults were collected in the study during 2012-2017/2018. In this study, the elderly were classified into 4 groups, moderate-to-severe group [<45 ml·min^-1·(1.73 m²)^-1], mild-to-moderate group [45- ml·min^-1·(1.73 m²)^-1], mild group [60- ml·min^-1·(1.73 m²)^-1] and normal group [≥90 ml·min^-1·(1.73 m²)^-1] according to their eGFR levels. Results: After 6 years of follow-up, 852 participants died, with a mortality rate of 47.3%. Multivariate Cox regression analysis showed that the levels of eGFR were negatively correlated with all-cause mortality risk in the elderly (the HR of elderly was 0.993 and the 95%CI was 0.989-0.997 for every unit of eGFR increased, P=0.001), while compared with the group with normal eGFR, the HRs (95%CI) of the elderly in the moderate-to-severe group, mild-to-moderate group, and mild group were 1.690 (1.224-2.332, P=0.001), 1.312 (0.978-1.758, P=0.070), 1.349 (1.047-1.737, P=0.020) respectively [trend test P<0.001]. Conclusion The decrease in eGFR was associated with higher mortality risk among the elderly in longevity areas in China.

Objective:To investigate the microenvironment associated with tumorimmunity in regenerated lymph nodes treated with VEGF-C, which involves the lymphangiogenesis, chemokine as well as alteration of cell populations.Methods:A total of 10 nude mice were randomized to 2 groups. 5 mice in group A were treated with autologous lymph nodes fragmentary transplantation together with VEGF-C, 5 mice without any intervention in group B were served as control group. 4 weeks after surgeries, MDA-MB-231-Luc-GFP cells (5×10 6 cells/mouse, 100 μl of 40% matrigel solution) were injected subcutaneously in the thoracic flunk of nude mice in group A, the same number cells were implanted into the second mammary fat pad in group B as well. 4 weeks post inoculation, the tumor draining lymph nodes (TDLNs) in both groups were harvested, and the microenvironment was assessed by hematoxylin-eosin (HE) staining and multispectral immunofluorescence staining for LYVE-1, chemokine CCL21, programmed death ligand-1(PD-L1) and F4/80. Results:The specific markers were analyzed based on positive cell percentage between group A and group B. The LYVE-1 and F4/80 expression in the group A was significantly higher than that in group B[LYVE-1: group A 21.44 0(34.675)% vs group B 2.964 (4.160)%, P<0.001; F4/80: group A 5.396 (7.205)% vs group B 3.573 (2.670)%, P=0.020)], and there were no significant differences in the expression of CCL21 and PD-L1 between these two groups [CCL21: group A 21.470((29.145)% vs group B 16.430((29.145)%( P=0.166); PD-L1: group A10.000 (14.430)%vs group B 4.070 (26.740)%, P=0.091]. Additionally, the double positive expression of LYVE-1/CCL21 and LYVE-1/F4/80 had still statistically significant differences[LYVE-1/CCL21: group A 8.637 (13.150)% vs group B 1.571 (1.680)%, P<0.001; LYVE-1/F4/80: group A 6.181 (9.050)% vs group B 1.454 (0.830)%, P<0.001], whereas, the two groups did not differ from each other in the double positive expression of LYVE-1/PD-L1 [group A 3.617 (4.195)% vs group B 2.363 (3.900)%, P=0.266]. Conclusions:The renewed lymph nodes treated with VEGF-C demonstrate some more immune suppressive conditions such as lymphatic endothelial cells hyperplasia, myeloid-derived suppressor cells infiltration, enhanced expression of CCL21 and PD-L1.

Objective:To investigate the microenvironment associated with tumorimmunity in regenerated lymph nodes treated with VEGF-C, which involves the lymphangiogenesis, chemokine as well as alteration of cell populations.Methods:A total of 10 nude mice were randomized to 2 groups. 5 mice in group A were treated with autologous lymph nodes fragmentary transplantation together with VEGF-C, 5 mice without any intervention in group B were served as control group. 4 weeks after surgeries, MDA-MB-231-Luc-GFP cells (5×10 6 cells/mouse, 100 μl of 40% matrigel solution) were injected subcutaneously in the thoracic flunk of nude mice in group A, the same number cells were implanted into the second mammary fat pad in group B as well. 4 weeks post inoculation, the tumor draining lymph nodes (TDLNs) in both groups were harvested, and the microenvironment was assessed by hematoxylin-eosin (HE) staining and multispectral immunofluorescence staining for LYVE-1, chemokine CCL21, programmed death ligand-1(PD-L1) and F4/80. Results:The specific markers were analyzed based on positive cell percentage between group A and group B. The LYVE-1 and F4/80 expression in the group A was significantly higher than that in group B[LYVE-1: group A 21.44 0(34.675)% vs group B 2.964 (4.160)%, P<0.001; F4/80: group A 5.396 (7.205)% vs group B 3.573 (2.670)%, P=0.020)], and there were no significant differences in the expression of CCL21 and PD-L1 between these two groups [CCL21: group A 21.470((29.145)% vs group B 16.430((29.145)%( P=0.166); PD-L1: group A10.000 (14.430)%vs group B 4.070 (26.740)%, P=0.091]. Additionally, the double positive expression of LYVE-1/CCL21 and LYVE-1/F4/80 had still statistically significant differences[LYVE-1/CCL21: group A 8.637 (13.150)% vs group B 1.571 (1.680)%, P<0.001; LYVE-1/F4/80: group A 6.181 (9.050)% vs group B 1.454 (0.830)%, P<0.001], whereas, the two groups did not differ from each other in the double positive expression of LYVE-1/PD-L1 [group A 3.617 (4.195)% vs group B 2.363 (3.900)%, P=0.266]. Conclusions:The renewed lymph nodes treated with VEGF-C demonstrate some more immune suppressive conditions such as lymphatic endothelial cells hyperplasia, myeloid-derived suppressor cells infiltration, enhanced expression of CCL21 and PD-L1.

Objective: Autologous lymph nodes fragmentary transplantation combined with vascular endothelial growth factor-C (VEGF-C) on athymic nude mice to explore the association between regeneration of lymphatic vessel and tumor cell migration. Methods: A total of 45 nude mice were randomly divided into 3 groups: Group A, simple autologous lymph nodes fragmentary transplantation, n=15; Group B, autologous lymph nodes fragmentary transplantation together with VEGF-C, n=15; Group C, without any intervention, n=15. At 1 month, 2 months and 6months after surgeries, the axillary lymph nodes of 5 mice in each group were dynamically examined by in vivo indocyanine green (ICG) fluorescence imaging respectively. The regenerated lymph nodes and relevant skin were evaluated using hematoxylin-eosin (H&E) staining and the skin was quantitatively analyzed via immunofluorescence staining for lymphatic vessel endothelial hyaluronan receptor 1(LYVE-1) as well. Results: One month after surgery, the right regenerated axillary lymph nodes in group B (5/5) were visible by in vivo ICG fluorescence imaging, whereas the same signals were not detected in group A (0/5). The results were the same at 2 and 6 months after surgery. HE staining showed that the cortical, paracortical, and medullary regions of the right axillary lymph nodes of the experimental group B were clear, and the lymphatic vessel structure was present, accompanied by lymphocyte infiltration. Immunofluorescence staining of the right upper limb showed that the expression of LYVE-1 in the lymphatic endothelium of the B group was significantly higher than that in group A (P<0.001) and the control group (both P<0.001). Conclusions Due to the promising consequence of regenerated lymph nodes, the procedure of autologous lymph nodes fragmentary transplantation combined with VEGF-C in athymic nude mice provides a reliable animal model for the next stage research.