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 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 analyze the epidemiological, etiological characteristics and transmission of an imported D8 genotype measles case in a child in Shandong Province, August 2023.Methods:A study was conducted on a measles case and 16 contacts in Shandong Province in August 2023. Field epidemiological surveys, including recent exposure and immunization history, were conducted. Serum and throat swab samples were collected from all 16 subjects. Measles IgM and IgG antibody levels and avidity were measured by ELISA, while virus detection and genotyping were performed using fluorescence quantitative PCR and RT-PCR. Genetic evolutionary analysis of the obtained sequences was conducted using MEGA and Beast software.Results:The case was an 11-year-old boy, a fifth-grade student, who developed symptoms on August 28, 2023. A total of five close contacts were investigated, including three family members (grandfather, father and sister) and two playmates. Additionally, 11 classmates who had close contact with the case′s sister during the infectious period (within five days after the rash onset) were also investigated. Among the 16 serum samples tested, only one case was positive for IgM, while the other 15 samples were negative for IgM. The results of the serum antibody avidity test showed that among the 16 serum samples, 14 were positive for IgG. Of these, eight had a relative avidity index >55%, indicating high-avidity antibodies; one had a relative avidity index <45%, indicating low-avidity antibodies; and five had an avidity index between 45% and 55%. The IgG detection OD values for the case′s sister and grandfather were higher than those of the other contacts. Based on the vaccination history of the subjects and the results of IgM and IgG tests, it was preliminarily determined that the case had a recent wild-type measles virus infection. The case′s sister and grandfather had a history of measles wild-type virus infection, while the high-avidity antibodies in the other contacts were likely induced by the measles vaccine. The results of the pharyngeal swab tests showed that only the case was positive for measles virus nucleic acid, while the remaining 15 samples were negative for measles virus. The genetic evolutionary analysis revealed that the viral sequence of this case (Mvs/Shandong.CHN/38.23) had a 100% homology with the Hong Kong strain sequence from August 2023. It belonged to a different transmission chain from the D8 genotype strains that appeared in Shandong Province between 2018 and 2019, with sequence homology ranging from 98.0% to 98.8%. The sequence homology within the transmission chain of this case was between 99.1% and 100%. The evolutionary rate of this transmission chain was approximately 8.38×10 -3 sub/site/year, and the most recent common ancestor was estimated to have emerged around the year 2011. Conclusion:This case is the first imported D8 genotype measles case in Shandong Province. There is no spatio-temporal correlation between this case and adult cases of D8 genotype imported from Shandong Province in 2018-2019, indicating a new D8 genotype imported epidemic.

Objective:To investigate how age and nail-tract volumetric bone mineral density (vBMD) are associated with postoperative mechanical performance of proximal femoral nail anti-rotation (PFNA-Ⅱ) fixation for geriatric intertrochanteric fractures using a finite-element analysis.Methods:Fifteen elderly patients with intertrochanteric fracture of the femur were selected for this study. They were 11 females and 4 males and divided into 5 groups based on their ages ( n=3): 55-year-old, 65-year-old, 75-year-old, 85-year-old, and 95-year-old groups. After three-dimensional models of the proximal femur were constructed using the preoperative CT data of their healthy contralateral hip, 31-A1.2 fractures of the AO/OTA type were created and PFNA-Ⅱ fixations simulated. Two loading schemes were created: graded quasi-static axial loads (700 N, 1,400 N, 2,100 N, and 2,800 N) were applied to compute equivalent plastic strain volumes in the femoral head region; displacement-controlled loading was applied to failure to derive load-displacement curves for stiffness and the maximum failure load. Nail-tract vBMD and regional hip vBMDs were measured by quantitative CT. Pearson correlation analysis was conducted to investigate the associations of age and nail-tract vBMD with the aforementioned mechanical indicators. Results:Under the same load, compared with the 55-year-old, 65-year-old, and 75-year-old groups, the plastic strain unit volumes of the fracture models in the 85-year-old and 95-year-old groups increased significantly. Under a load of 700 N, no plastic strain was observed in the fracture models in the 55-year-old, 65-year-old, and 75-year-old groups, while an average plastic strain of approximately 50 mm 3 was observed in the fracture models in the 85-year-old group. Under a load of 2,800 N, the high strain areas in the fracture models in the 85-year-old and 95-year-old groups were mainly concentrated at the tip of the head nail and the junction between the head nail and the main nail. Load-displacement curves showed a marked reduction in the failure load in patients aged ≥85 years. Under loads of 1,400 N, 2,100 N, and 2,800 N, there was a strong association between the nail-tract vBMD and the volume of the plastic strain unit ( r=-0.82, -0.88, -0.89, respectively), which was stronger than those for total-hip vBMD. Conclusions:Finite-element analysis indicates that age and nail-tract vBMD are closely related to local plastic strain and overall stiffness of the proximal femur after PFNA-Ⅱ fixation for the geriatric intertrochanteric fractures. Patients aged ≥85 years old are more prone to plastic yielding, which compromises fixation stability.

Objective:To analyze the epidemiological, etiological characteristics and transmission of an imported D8 genotype measles case in a child in Shandong Province, August 2023.Methods:A study was conducted on a measles case and 16 contacts in Shandong Province in August 2023. Field epidemiological surveys, including recent exposure and immunization history, were conducted. Serum and throat swab samples were collected from all 16 subjects. Measles IgM and IgG antibody levels and avidity were measured by ELISA, while virus detection and genotyping were performed using fluorescence quantitative PCR and RT-PCR. Genetic evolutionary analysis of the obtained sequences was conducted using MEGA and Beast software.Results:The case was an 11-year-old boy, a fifth-grade student, who developed symptoms on August 28, 2023. A total of five close contacts were investigated, including three family members (grandfather, father and sister) and two playmates. Additionally, 11 classmates who had close contact with the case′s sister during the infectious period (within five days after the rash onset) were also investigated. Among the 16 serum samples tested, only one case was positive for IgM, while the other 15 samples were negative for IgM. The results of the serum antibody avidity test showed that among the 16 serum samples, 14 were positive for IgG. Of these, eight had a relative avidity index >55%, indicating high-avidity antibodies; one had a relative avidity index <45%, indicating low-avidity antibodies; and five had an avidity index between 45% and 55%. The IgG detection OD values for the case′s sister and grandfather were higher than those of the other contacts. Based on the vaccination history of the subjects and the results of IgM and IgG tests, it was preliminarily determined that the case had a recent wild-type measles virus infection. The case′s sister and grandfather had a history of measles wild-type virus infection, while the high-avidity antibodies in the other contacts were likely induced by the measles vaccine. The results of the pharyngeal swab tests showed that only the case was positive for measles virus nucleic acid, while the remaining 15 samples were negative for measles virus. The genetic evolutionary analysis revealed that the viral sequence of this case (Mvs/Shandong.CHN/38.23) had a 100% homology with the Hong Kong strain sequence from August 2023. It belonged to a different transmission chain from the D8 genotype strains that appeared in Shandong Province between 2018 and 2019, with sequence homology ranging from 98.0% to 98.8%. The sequence homology within the transmission chain of this case was between 99.1% and 100%. The evolutionary rate of this transmission chain was approximately 8.38×10 -3 sub/site/year, and the most recent common ancestor was estimated to have emerged around the year 2011. Conclusion:This case is the first imported D8 genotype measles case in Shandong Province. There is no spatio-temporal correlation between this case and adult cases of D8 genotype imported from Shandong Province in 2018-2019, indicating a new D8 genotype imported epidemic.

Objective:To investigate how age and nail-tract volumetric bone mineral density (vBMD) are associated with postoperative mechanical performance of proximal femoral nail anti-rotation (PFNA-Ⅱ) fixation for geriatric intertrochanteric fractures using a finite-element analysis.Methods:Fifteen elderly patients with intertrochanteric fracture of the femur were selected for this study. They were 11 females and 4 males and divided into 5 groups based on their ages ( n=3): 55-year-old, 65-year-old, 75-year-old, 85-year-old, and 95-year-old groups. After three-dimensional models of the proximal femur were constructed using the preoperative CT data of their healthy contralateral hip, 31-A1.2 fractures of the AO/OTA type were created and PFNA-Ⅱ fixations simulated. Two loading schemes were created: graded quasi-static axial loads (700 N, 1,400 N, 2,100 N, and 2,800 N) were applied to compute equivalent plastic strain volumes in the femoral head region; displacement-controlled loading was applied to failure to derive load-displacement curves for stiffness and the maximum failure load. Nail-tract vBMD and regional hip vBMDs were measured by quantitative CT. Pearson correlation analysis was conducted to investigate the associations of age and nail-tract vBMD with the aforementioned mechanical indicators. Results:Under the same load, compared with the 55-year-old, 65-year-old, and 75-year-old groups, the plastic strain unit volumes of the fracture models in the 85-year-old and 95-year-old groups increased significantly. Under a load of 700 N, no plastic strain was observed in the fracture models in the 55-year-old, 65-year-old, and 75-year-old groups, while an average plastic strain of approximately 50 mm 3 was observed in the fracture models in the 85-year-old group. Under a load of 2,800 N, the high strain areas in the fracture models in the 85-year-old and 95-year-old groups were mainly concentrated at the tip of the head nail and the junction between the head nail and the main nail. Load-displacement curves showed a marked reduction in the failure load in patients aged ≥85 years. Under loads of 1,400 N, 2,100 N, and 2,800 N, there was a strong association between the nail-tract vBMD and the volume of the plastic strain unit ( r=-0.82, -0.88, -0.89, respectively), which was stronger than those for total-hip vBMD. Conclusions:Finite-element analysis indicates that age and nail-tract vBMD are closely related to local plastic strain and overall stiffness of the proximal femur after PFNA-Ⅱ fixation for the geriatric intertrochanteric fractures. Patients aged ≥85 years old are more prone to plastic yielding, which compromises fixation stability.

Objective:To explore the application and clinical significance of Automatic Functional Imaging (AFI) technology in evaluating left ventricular and left atrial damage in patients with alcoholic cardiomyopathy.Methods:A total of 120 patients with alcoholic cardiomyopathy who visited the Affiliated Hospital of Jining Medical University from April 2021 to March 2023 were selected, including 40 patients with mild, moderate, and severe alcohol consumption each. At the same time, 40 healthy volunteers who did not drink alcohol were selected as controls. All subjects underwent ultrasound examination, and the differences in two-dimensional ultrasound and AFI parameters among the groups were analyzed. Pearson correlation analysis was used to evaluate the correlation between AFI parameters and two-dimensional ultrasound parameters. The diagnostic value of global long axis peak systolic strain (GLPS) of the left ventricle in alcoholic cardiomyopathy was analyzed using receiver operating characteristic (ROC) curves.Results:The left ventricular end diastolic diameter (LVDd), left ventricular end systolic diameter (LVDS), end diastolic interventricular septal thickness (IVSTd), end diastolic left ventricular posterior wall thickness (PWTd), left atrial minimum volume (LAVmin), left atrial maximum volume (LAVmax), and left atrial active pre systolic volume (LAVp) in the severe group were significantly larger than those in the control group, mild group, and moderate group (all P<0.05), while the left ventricular ejection fraction (LVEF) and the ratio of E peak velocity to A peak velocity (E/A) were significantly smaller than those in the control group, mild group, and moderate group (all P<0.05); The left ventricular end diastolic volume (LVEDV), left ventricular end systolic volume (LVESV), left ventricular mass index (LVMI), LAVmin, LAVmax, and LAVp in the moderate and severe groups were significantly higher than those in the control and mild groups (all P<0.05); There was no statistically significant difference in LVDd, LVDS, IVSTd, PWTd, and LVEF among the control group, mild group, and moderate group (all P>0.05). The GLPS levels in the mild, moderate, and severe groups were significantly higher than those in the control group (all P<0.05), with the severe group having significantly higher GLPS levels than the mild and moderate groups ( P<0.05); There was no statistically significant difference in peak strain dispersion (PSD) among the control group, mild group, moderate group, and severe group (all P>0.05). GLPS was negatively correlated with LVEF ( r=-0.441, P<0.05), while GLPS was positively correlated with LVMI ( r=0.504, P<0.05). The area under the ROC curve for diagnosing alcoholic cardiomyopathy with GLPS was 0.912 (95% CI: 0.869-0.955, P<0.05), with a cutoff value of -20.16, sensitivity and specificity of 76.70% and 95.00%, respectively. Conclusions:The mechanical properties of the left ventricle and left atrium in patients with alcoholic cardiomyopathy are significantly altered, and AFI parameters have certain application value in the diagnosis of alcoholic cardiomyopathy.

Opioid-free anesthesia(OFA)is a multimodal analgesic strategy that combines multiple non-opioid drugs and/or techniques to obtain high-quality anesthesia.With the popularization of the concept of enhanced recovery after surgery(ERAS),OFA has become a common concern hot spot for perioperative phy-sicians.OFA is in line with the ERAS concept,and under multimodal anesthesia and pain management,it can reduce surgical stress,inflammation reaction and postoperative complications,significantly improve the prog-nosis of patients,promote postoperative rapid recovery and reduce the burden of medical and health resources.This article reviews the adverse reactions of opioids,OFA concept and indications,the clinical application of OFA in recent years,the existing controversies and problems to be solved.

ObjectiveTo investigate the prevalence of stroke in Songjiang District from 2017 to 2022, to analyze the epidemiological characteristics of stroke incidence, so as to provide a scientific basis for the formulation of stroke prevention and control policies. MethodsData of new stroke incidence from 2017 to 2022 in Songjiang District were obtained from the Shanghai Stroke and Acute Myocardial Infarction Registration and Reporting Information System. In addition, different classifications such as time of onset, gender, age group and types of stroke, were statistically analyzed. Statistical indicators, such as the number of incidence, crude incidence rate, standardized incidence rate and average age of incidence were calculated simultaneously. Joinpoint software were used to calculate the annual change percentage (APC) and the trend of stroke incidence in Songjiang District. ResultsFrom 2017 to 2022, the newly reported cases of stroke were 12 988 in Songjiang District, the crude incidence rate was 325.76/10⁵, and the standardized incidence rate was 127.58/10⁵. The crude incidence rate and standardized incidence rate in males were 363.45/10⁵ and 157.17/10⁵, respectively, but 288.68/10⁵ and 99.02/10⁵ in females. The mean age of onset was (73.12±11.75) years, of which the mean age of onset was (70.86±11.96) years for men and (75.91±10.85) years for women. The incidence of stroke increased with age, rising rapidly after 60 years and reaching a peak in the age group of ≥ 80 years old. The crude incidence rate and standardized incidence rate of stroke in Songjiang District showed a downward trend from 2017 to 2022, with an APC of -6.20% and -8.01%, respectively (P=0.018, 0.007). The newly reported stroke was dominated by ischemic stroke, accounting for 82.81% of the total cases, with a crude incidence rate of 269.77/10⁵ and a standardized rate of 103.84/10⁵. The incidence of stroke presented seasonal characteristics, with the highest incidence in winter, accounting for 26.11% of the whole year. ConclusionThe incidence rate of stroke in Songjiang District shows a declined trend, but the overall incidence is still at a high level. The situation of prevention and control is still serious, with a heavy disease burden. It is necessary to strengthen health education and disease management for the elderly.

Purpose: Tamoxifen showed individual differences in efficacy under different CYP2D6*10 genotypes. Our study evaluated the prognosis of tamoxifen or toremifene in hormone receptor (HR)–positive breast cancer patients under different genotypes. Materials and Methods: CYP2D6*10 genotypes of HR-positive breast cancer patients were determined by Sanger sequencing, and all the patients were divided into tamoxifen group or toremifene group. Results: A total of 268 patients with HR-positive breast cancer were studied. The median follow-up time was 72.0 months (range, 5.0 to 88.0 months). Of these, 88 (32.9%), 114 (42.5%), and 66 (24.6%) patients had C/C, C/T, and T/T genotypes, respectively. Among patients who received tamoxifen (n=176), the 5-year disease-free survival (DFS) rate in patients with C/C and C/T genotype was better than that in patients with T/T genotype, and the difference was statistically significant (p < 0.001 and p=0.030, respectively). In patients receiving toremifene, CYP2D6*10 genotype was not significantly associated with DFS (p=0.325). Regardless of genotypes, the 5-year DFS rate was higher in patients treated with toremifene than in patients with tamoxifen (91.3% vs. 80.0%, p=0.011). Compared with tamoxifen, toremifene remained an independent prognostic marker of DFS in multivariate analysis (hazard ratio, 0.422; p=0.021). For all the 180 patients with CYP2D6*10 C/T and T/T genotypes, the 5-year DFS rate was significantly higher in the toremifene group than in the tamoxifen group (90.8% vs. 70.1%, p=0.003). Conclusion Toremifene may be an alternative adjuvant endocrine therapy for patients with CYP2D6*10 mutant genotypes.