OBJECTIVES: To evaluate the protective effect of Schistosoma japonicum cystatin (rSj-Cystatin) in a mouse mode of "two-hit" sepsis. METHODS: Sixty male C57BL/6 mice randomized equally into sham-operated group, protein group, "two-hit" modeling group, and protein intervention group. In the former two groups, the mice received an intraperitoneal injection of 100 μL PBS followed by exposure of the cecum and then by intraperitoneal injection of 100 μL PBS or 25 μg rSj-Cystatin 30 min later; In the latter two groups, 100 μL PBS containing LPS (5 mg/kg) was injected intraperitoneally 24 h before cecal ligation and puncture (CLP), and 100 μL PBS or 25 μg rSj-Cystatin were injected 30 min after CLP. At 12 h after rSj-Cystatin treatment, 6 mice from each group were sacrificed for detection of TNF-α, IL-6, IL-10, TGF-β, iNOS and Arg-1 in the serum, spleen, liver, lung and kidney tissues using ELISA, for examinations of liver, lung and kidney pathologies with HE staining, and for analysis of CD3⁺CD4⁺CD25⁺Foxp3⁺ T cell percentage in the spleen using flow cytometry. The remaining mice were observed for general condition and 72-h survival. RESULTS: The 72-h survival rates in the 4 groups were 100%, 100%, 0% and 20%, respectively, showing significant differences between the latter two groups. The mouse models of "two-hit" sepsis exhibited obvious tissue pathologies and significant elevations of TNF-α and IL-6 in both the serum and tissue homogenate, which were significantly ameliorated by rSj-Cystatin treatment. Treatment with rSj-Cystatin also increased IL-10 and TGF-β levels and spleen CD3⁺CD4⁺CD25⁺Foxp3⁺ T cell percentage. The septic mouse models also showed increased iNOS levels in all the detected tissues and a decreased Arg-1 level in the kidney, and these changes were obviously improved by rSj-Cystatin treatment. CONCLUSIONS rSj-Cystatin has a protective effect against "two-hit" sepsis in mice by regulating the inflammatory microenvironment.
Animals ; Mice ; Sepsis/drug therapy* ; Male ; Schistosoma japonicum/chemistry* ; Mice, Inbred C57BL ; Cystatins/therapeutic use* ; Interleukin-10/metabolism* ; Interleukin-6/blood* ; Tumor Necrosis Factor-alpha/blood* ; Disease Models, Animal ; Transforming Growth Factor beta/metabolism*

Objective:To explore the safety and efficacy of shunt reduction using the Interlock-35 fibered interlocking detachable coil (IDC) occlusion system in the treatment of refractory hepatic encephalopathy (HE) after transjugular intrahepatic portosystemic shunt (TIPS).Methods:From August 2022 to December 2023, at the Department of Gastroenterology of the Air Force Medical Center, the clinical data of patients with refractory HE after TIPS who were treated with shunt reduction using the Interlock-35 fibered IDC occlusion system were retrospectively collected, which included portal vein pressure gradient (PVPG), HE grades, blood ammonia levels, prothrombin time (PT), liver function parameters, and other related indicators. The primary indicators related to the efficacy of the shunt reduction included symptom improvement, and changes in PVPG, blood ammonia levels, and Child-Pugh score. The safety of shunt reduction was analyzed based on the incidence of complications such as gastrointestinal bleeding and ascites during the follow-up period. Paired t-test was used for statistical analysis. Results:A total of 21 patients were enrolled. Prior to shunt reduction, there were 5 cases with HE of grade 3 and 16 cases with HE of grade 2. Before operation, the blood ammonia was (103.14±27.69) mol/L; and the liver function Child-Pugh grade of 1 case was classified as grade A, 16 cases as grade B, and 4 cases as grade C. Shunt reduction was performed between 7 and 1 879 d, with a median time of 99 (54, 806) d after TIPS. The procedure was technically successful in all patients, with a total of 25 coils implanted. Before shunt reduction, the PVPG was (14.02±5.28) cmH 2O (1 cmH 2O=0.098 kPa), after shunt reduction procedure, the PVPG increased to (25.05±6.04) cmH 2O, and the difference was statistically significant ( t=-11.26, P<0.001). After operation, 16 patients returned to the hospital for follow-up examinations, with a median follow-up time of 114 (46, 195) d, the blood ammonia levels, PT, and Child-Pugh scores during the follow-up were all lower than those before operation ((78.19±27.85) μmol/L vs. (105.00±30.53) μmol/L, (14.09±1.65) s vs. (15.41±2.35) s, and 6.88±1.59 vs. 8.13±1.75, respectively), and the differences were statistically significant ( t=2.23, 3.23, and 2.61; P=0.040, <0.001, =0.020). There was no statistically significant in PVPG between during follow-up and immediately post-procedure ((28.91±6.20) cmH 2O vs. (25.22±5.92) cmH 2O, P>0.05). During the follow-up period, HE symptoms disappeared in 12 patients among the 16 patients who returned to hospital for follow-up, however gastrointestinal bleeding occurred in 5 patients and ascites occurred in 3 patients; additionally, 4 patients experienced intermittent HE symptoms (grade 1 in 3 cases, grade 2 in 1 case). After operation, 5 patients were followed up via telephone, among them, 3 patients died, and 2 patients experienced intermittent HE (grade 1) which could be spontaneously restored with dietary adjustments and(or) medication. Conclusions:Interlock-35 fibered IDC occlusion system for shunt reduction is a feasible and effective treatment for refractory HE after TIPS. It can effectively improve symptoms and decrease liver function score. After shunt reduction, early follow-up and adjustment of flow reduction can help reduce the occurrence of severe complications.

Objective To evaluate the protective effect of Schistosoma japonicum cystatin(rSj-Cystatin)in a mouse mode of"two-hit"sepsis.Methods Sixty male C57BL/6 mice randomized equally into sham-operated group,protein group,"two-hit"modeling group,and protein intervention group.In the former two groups,the mice received an intraperitoneal injection of 100 μL PBS followed by exposure of the cecum and then by intraperitoneal injection of 100 μL PBS or 25 μg rSj-Cystatin 30 min later;In the latter two groups,100 μL PBS containing LPS(5 mg/kg)was injected intraperitoneally 24 h before cecal ligation and puncture(CLP),and 100 μL PBS or 25 μg rSj-Cystatin were injected 30 min after CLP.At 12 h after rSj-Cystatin treatment,6 mice from each group were sacrificed for detection of TNF-α,IL-6,IL-10,TGF-β,iNOS and Arg-1 in the serum,spleen,liver,lung and kidney tissues using ELISA,for examinations of liver,lung and kidney pathologies with HE staining,and for analysis of CD3+CD4+CD25+Foxp3+T cell percentage in the spleen using flow cytometry.The remaining mice were observed for general condition and 72-h survival.Results The 72-h survival rates in the 4 groups were 100％,100％,0％and 20％,respectively,showing significant differences between the latter two groups.The mouse models of"two-hit"sepsis exhibited obvious tissue pathologies and significant elevations of TNF-α and IL-6 in both the serum and tissue homogenate,which were significantly ameliorated by rSj-Cystatin treatment.Treatment with rSj-Cystatin also increased IL-10 and TGF-β levels and spleen CD3+CD4+CD25+Foxp3+T cell percentage.The septic mouse models also showed increased iNOS levels in all the detected tissues and a decreased Arg-1 level in the kidney,and these changes were obviously improved by rSj-Cystatin treatment.Conclusion rSj-Cystatin has a protective effect against"two-hit"sepsis in mice by regulating the inflammatory microenvironment.

Objective:To explore the association between healthy lifestyle and co-morbidity of overweight/obesity and myopia in adolescents.Methods:Based on the Shanghai Municipal Dynamic Cohort of Student Common Diseases, we used the group-based trajectory model (GBTM) to establish a model for the development of adolescents' healthy lifestyle trajectories aged 11-14 years and the Cox proportional hazard regression model to assess the effects of different healthy lifestyles on the co-morbidity of overweight/obesity and myopia in adolescents.Results:A total of 2 331 adolescents were included in the analysis. The average follow-up time was 1.87 years, with age of (11.44±0.45) years at the initial follow-up, among 1 106 boys and 1 225 girls. During the 2-year follow-up period, the incidence rates of overweight/obesity, myopia, and co-occurrence of overweight/obesity and myopia were 25.9%, 77.0%, and 13.7%, respectively. GBTM identified 3 healthy lifestyles: the unhealthy group (7.3%), the relatively healthy group (50.2%), and the healthy group (42.5%). The risk of overweight/obesity was lower in the relatively healthy group than in the unhealthy group ( HR=0.694, 95% CI: 0.508-0.947). There was no statistically significant association between the GBTM lifestyle subgroups and myopia ( P>0.05). The risk of co-occurrence of overweight/obesity and myopia was lower in both relatively healthy group and healthy group than in the unhealthy group (relatively healthy group: HR=0.515, 95% CI: 0.348-0.763; healthy group: HR=0.571, 95% CI: 0.384-0.849). Sensitivity analyses showed this result to be stable for myopia, overweight/obesity and myopia co-morbidities. Conclusion:Persistent unhealthy lifestyle increases the risk of overweight/obesity and myopia co-occurrence in adolescents.

Objective To investigate the effects of Demodex infection on clinical symptoms,signs,and tear MMP-9 levels in patients with meibomian gland dysfunction(MGD).Methods A total of 680 patients with MGD were selected from our hospital,including 162 males and 518 females,with an average age of(45.05±15.41)years old.The patients were divided into two groups based on the presence of Demodex mite infestation:the Demodex positive group(340 cases)and the Demodex negative group(340 cases).All patients underwent evaluations using the OSDI questionnaire,SPEED questionnaire,eyelid margin alteration score,corneal fluorescein staining score,tear MMP-9 measurement,meibomian gland orifice score,meibomian gland excretion ability score,meibomian gland secretion score,meibomian gland loss score,tear film breakup time(BUT),and Schirmer I tear secretion test.The differences in these indicators between the two groups were compared.Results SPEED questionnaire score:Demodex positive group:(7.68±2.80),Demodex negative group:(6.28±1.99).There was a statistically significant difference between the two groups(t=2.582,P=0.012).Eyelid margin alteration score:Demodex positive group:(3.63±1.53),Demodex negative group:(2.85±0.77).A statistically significant difference was observed(t=2.861,P=0.006).Corneal fluorescein staining score:Demodex positive group:(2.25±1.86),Demodex negative group:(1.08±1.33).There was a statistically significant difference(t=3.247,P=0.002).Tear MMP-9 content:Demodex positive group:(30.76±43.14)ng/mL,Demodex negative group:(12.36±12.10)ng/mL.A statistically significant difference was found(t=2.598,P=0.013).No statistically significant differences were observed between the Demodex positive and negative groups in meibomian gland orifice score,meibomian gland excretion ability score,meibomian gland secretion score,meibomian gland loss score,BUT,tear secretion examination,and age comparison(P>0.05).Conclusions Demodex mite infestation in patients with MGD exhibits significant differ-ences across various clinical indicators,notably in SPEED questionnaire scores,eyelid margin alterations,corneal fluorescein staining,and tear MMP-9 levels.These changes are associated with mechanisms including inflammatory responses,cellular damage,and immune dysregulation.Demodex mite infestation may significantly influence the clinical progression of MGD by exacerbating inflammation and symptom severity,potentially playing a crucial role in disease development.

Objective:To explore the association between healthy lifestyle and co-morbidity of overweight/obesity and myopia in adolescents.Methods:Based on the Shanghai Municipal Dynamic Cohort of Student Common Diseases, we used the group-based trajectory model (GBTM) to establish a model for the development of adolescents' healthy lifestyle trajectories aged 11-14 years and the Cox proportional hazard regression model to assess the effects of different healthy lifestyles on the co-morbidity of overweight/obesity and myopia in adolescents.Results:A total of 2 331 adolescents were included in the analysis. The average follow-up time was 1.87 years, with age of (11.44±0.45) years at the initial follow-up, among 1 106 boys and 1 225 girls. During the 2-year follow-up period, the incidence rates of overweight/obesity, myopia, and co-occurrence of overweight/obesity and myopia were 25.9%, 77.0%, and 13.7%, respectively. GBTM identified 3 healthy lifestyles: the unhealthy group (7.3%), the relatively healthy group (50.2%), and the healthy group (42.5%). The risk of overweight/obesity was lower in the relatively healthy group than in the unhealthy group ( HR=0.694, 95% CI: 0.508-0.947). There was no statistically significant association between the GBTM lifestyle subgroups and myopia ( P>0.05). The risk of co-occurrence of overweight/obesity and myopia was lower in both relatively healthy group and healthy group than in the unhealthy group (relatively healthy group: HR=0.515, 95% CI: 0.348-0.763; healthy group: HR=0.571, 95% CI: 0.384-0.849). Sensitivity analyses showed this result to be stable for myopia, overweight/obesity and myopia co-morbidities. Conclusion:Persistent unhealthy lifestyle increases the risk of overweight/obesity and myopia co-occurrence in adolescents.

OBJECTIVE To investigate the improvement effect and mechanism of desloratadine citrate disodium in mice with hypersensitivity pneumonitis(HP).METHODS Sixty mice were randomly divided into blank control group(normal saline),model group(normal saline),prednisone group(positive control,20 mg/kg)and desloratadine citrate disodium low-,medium-and high-dose groups(0.5,1,2 mg/kg),with 10 mice in each group.Except for the blank control group,mice in other groups were intraperitoneally injected with ovalbumin(OVA)and exposed to OVA inhalation to establish the HP model.On day 22 post-modeling,mice in each group were administered the corresponding drugs or normal saline,once a day,for 11 consecutive days.After the last administration,lung function and airway hyperreactivity were assessed.The levels of interleukin-1β(IL-1β),IL-4 and IL-6 in serum as well as the levels of IL-8,IL-13 and IL-17A in bronchoalveolar lavage fluid were determined.Pathological changes in lung tissue of mice were evaluated using Masson staining.Furthermore,the expressions of fibrosis-related proteins,including transforming growth factor β1(TGF-β1),type Ⅲ collagen(Col-Ⅲ)and fibronectin(FN)were determined in lung tissues.RESULTS Compared with the blank control group,the model group showed significant deterioration in lung function(P＜0.01),while airway resistance and serum levels of IL-1β,IL-4,IL-6 and the levels of IL-8,IL-13 and IL-17A in the bronchoalveolar lavage fluid were increased significantly(P＜0.01).The lung tissues exhibited alveolar collapse,atrophy,and structural disarray,along with the formation of extensive deposits of blue collagen fibers,the percentage of positive staining increased significantly(P＜0.01).Additionally,the expression levels of TGF-β1,Col-Ⅲ,and FN proteins in the lung tissues were also increased significantly(P＜0.01).After intervention with desloratadine citrate disodium,the pathological changes in the lung tissues of mice in each dosage group of desloratadine citrate disodium showed varying degrees of improvement,and most of the aforementioned indicator levels were significantly reversed(P＜0.05 or P＜0.01).CONCLUSIONS Desloratadine citrate disodium can improve the lung function and airway hyperreactivity of HP mice,inhibit the release of inflammatory factors in serum and bronchoalveolar lavage fluid,and reduce the deposition of collagen fibers.Its mechanism of action may be related to anti-inflammatory,immunomodulatory,and antifibrotic effects.

Objective To investigate the effects of Demodex infection on clinical symptoms,signs,and tear MMP-9 levels in patients with meibomian gland dysfunction(MGD).Methods A total of 680 patients with MGD were selected from our hospital,including 162 males and 518 females,with an average age of(45.05±15.41)years old.The patients were divided into two groups based on the presence of Demodex mite infestation:the Demodex positive group(340 cases)and the Demodex negative group(340 cases).All patients underwent evaluations using the OSDI questionnaire,SPEED questionnaire,eyelid margin alteration score,corneal fluorescein staining score,tear MMP-9 measurement,meibomian gland orifice score,meibomian gland excretion ability score,meibomian gland secretion score,meibomian gland loss score,tear film breakup time(BUT),and Schirmer I tear secretion test.The differences in these indicators between the two groups were compared.Results SPEED questionnaire score:Demodex positive group:(7.68±2.80),Demodex negative group:(6.28±1.99).There was a statistically significant difference between the two groups(t=2.582,P=0.012).Eyelid margin alteration score:Demodex positive group:(3.63±1.53),Demodex negative group:(2.85±0.77).A statistically significant difference was observed(t=2.861,P=0.006).Corneal fluorescein staining score:Demodex positive group:(2.25±1.86),Demodex negative group:(1.08±1.33).There was a statistically significant difference(t=3.247,P=0.002).Tear MMP-9 content:Demodex positive group:(30.76±43.14)ng/mL,Demodex negative group:(12.36±12.10)ng/mL.A statistically significant difference was found(t=2.598,P=0.013).No statistically significant differences were observed between the Demodex positive and negative groups in meibomian gland orifice score,meibomian gland excretion ability score,meibomian gland secretion score,meibomian gland loss score,BUT,tear secretion examination,and age comparison(P>0.05).Conclusions Demodex mite infestation in patients with MGD exhibits significant differ-ences across various clinical indicators,notably in SPEED questionnaire scores,eyelid margin alterations,corneal fluorescein staining,and tear MMP-9 levels.These changes are associated with mechanisms including inflammatory responses,cellular damage,and immune dysregulation.Demodex mite infestation may significantly influence the clinical progression of MGD by exacerbating inflammation and symptom severity,potentially playing a crucial role in disease development.

Objective:To explore the safety and efficacy of shunt reduction using the Interlock-35 fibered interlocking detachable coil (IDC) occlusion system in the treatment of refractory hepatic encephalopathy (HE) after transjugular intrahepatic portosystemic shunt (TIPS).Methods:From August 2022 to December 2023, at the Department of Gastroenterology of the Air Force Medical Center, the clinical data of patients with refractory HE after TIPS who were treated with shunt reduction using the Interlock-35 fibered IDC occlusion system were retrospectively collected, which included portal vein pressure gradient (PVPG), HE grades, blood ammonia levels, prothrombin time (PT), liver function parameters, and other related indicators. The primary indicators related to the efficacy of the shunt reduction included symptom improvement, and changes in PVPG, blood ammonia levels, and Child-Pugh score. The safety of shunt reduction was analyzed based on the incidence of complications such as gastrointestinal bleeding and ascites during the follow-up period. Paired t-test was used for statistical analysis. Results:A total of 21 patients were enrolled. Prior to shunt reduction, there were 5 cases with HE of grade 3 and 16 cases with HE of grade 2. Before operation, the blood ammonia was (103.14±27.69) mol/L; and the liver function Child-Pugh grade of 1 case was classified as grade A, 16 cases as grade B, and 4 cases as grade C. Shunt reduction was performed between 7 and 1 879 d, with a median time of 99 (54, 806) d after TIPS. The procedure was technically successful in all patients, with a total of 25 coils implanted. Before shunt reduction, the PVPG was (14.02±5.28) cmH 2O (1 cmH 2O=0.098 kPa), after shunt reduction procedure, the PVPG increased to (25.05±6.04) cmH 2O, and the difference was statistically significant ( t=-11.26, P<0.001). After operation, 16 patients returned to the hospital for follow-up examinations, with a median follow-up time of 114 (46, 195) d, the blood ammonia levels, PT, and Child-Pugh scores during the follow-up were all lower than those before operation ((78.19±27.85) μmol/L vs. (105.00±30.53) μmol/L, (14.09±1.65) s vs. (15.41±2.35) s, and 6.88±1.59 vs. 8.13±1.75, respectively), and the differences were statistically significant ( t=2.23, 3.23, and 2.61; P=0.040, <0.001, =0.020). There was no statistically significant in PVPG between during follow-up and immediately post-procedure ((28.91±6.20) cmH 2O vs. (25.22±5.92) cmH 2O, P>0.05). During the follow-up period, HE symptoms disappeared in 12 patients among the 16 patients who returned to hospital for follow-up, however gastrointestinal bleeding occurred in 5 patients and ascites occurred in 3 patients; additionally, 4 patients experienced intermittent HE symptoms (grade 1 in 3 cases, grade 2 in 1 case). After operation, 5 patients were followed up via telephone, among them, 3 patients died, and 2 patients experienced intermittent HE (grade 1) which could be spontaneously restored with dietary adjustments and(or) medication. Conclusions:Interlock-35 fibered IDC occlusion system for shunt reduction is a feasible and effective treatment for refractory HE after TIPS. It can effectively improve symptoms and decrease liver function score. After shunt reduction, early follow-up and adjustment of flow reduction can help reduce the occurrence of severe complications.

Objective:To conduct a phased summary and analysis of the operation and quality control (QC) of the first human milk bank (HMB) in East China over a ten-year period.Methods:Data on the operation of the HMB at Women's Hospital of Nanjing Medical University, characteristics of donors and recipients, clinical application of donated milk, and operational costs from August 1, 2013, to July 31, 2023, were collected, organized, analyzed, and described. Quality and safety management of the HMB began in 2016, with QC measures implemented. Chi-square tests were used to compare data related to the operation of the HMB, donors, and recipient infants before QC (2013-2015) and after QC (2016-2023). Results:Over the ten-year period since its establishment, the HMB received donor human milk (DHM) from 1 974 donors, totaling 9 390.41 liters. The qualification rate of donors was 86.47% (1 707/1 974), with a qualification rate of DHM of 98.01% (9 203.21/9 390.41) and 21 757 donation instances, with the highest individual donation count reaching 195 times. In the past 10 years, due to the epidemic of the new coronavirus in 2020, the number of milk donors, the amount of DHM and the total number of milk donations decreased significantly, but the amount of DHM per capita and the number of milk donations per capita showed a continuous upward trend. Compared to the period before QC, the qualification rate of donors [96.75% (1 253/1 295) vs. 66.86% (454/679), χ 2=340.33, P<0.001] and the qualification rate of DHM [98.19% (8 366.76/8 521.08) vs. 96.22% (836.45/869.33), χ 2=16.33, P<0.001] both improved after QC. A total of 11 197 recipients received 6 615.38 liters of DHM, with a utilization rate of 71.88% (6 615.38/9 203.21). The current operation mode of the HMB is "voluntary donation, free use". Over ten years, the costs for consumables, testing, labor, energy, and fixed assets amounted to 9.36 million CNY, with an operational cost of 996.32 CNY per liter (9.36 million/9 390.41 L) and approximately 1.00 CNY per milliliter of DHM. Conclusions:The hospital's HMB has been operating stably for ten years, and abundant DHM benefits many newborns. QC measures have effectively increased the qualification rates of both donors and DHM, providing better nutritional support for the treatment of critically ill infants. However, the operational costs of the HMB are relatively high, necessitating the exploration of an operational model suitable for China's national conditions.