Objective To evaluate the efficacy of a combined immunosuppression regimen in modulating rejection in genetically modified pig-to-macaque xenogeneic heart transplantation.Methods Two xenogeneic heart transplantation models were constructed using genetically modified pigs and macaques.Dynamic monitoring of recipient peripheral blood immune parameters and observation of graft pathological changes were performed.Results Regimen 1,featuring B-cell depletion,T-cell inhibition,and C3 complement suppression,reduced lymphocyte levels but failed to control acute humoral rejection and macrophage infiltration.Regimen 2,adding C5 complement inhibition and interleukin-6 inhibition to Regimen 1,more effectively lowered lymphocyte levels,inhibited acute humoral rejection and complement activation,and decreased antibody deposition.However,a late-phase cytokine storm and residual T cells emerged.Conclusions Regimen 2 reduces the hyperacute and acute rejection risks through multi-target intervention.Yet,it requires balancing medication complexity and safety.This indicates the need to optimize cellular immune regulation and adjust the plan through dynamic multidimensional monitoring.

Objective To investigate the biomechanical characteristics of Salto Talaris tibial components with different heights at the bone-prosthesis interface during different gait support phases after total ankle replacement.Methods An ankle joint model was reconstructed using a weight-bearing CT from a 61-year-old female patient with ankle arthritis,and Salto Talaris tibial components with different heights(5,7,9,11 mm)were modelled to simulate the loading of the tibial-prosthesis during four gait support phases,and to analyse the micromotion and stresses at the bone-prosthesis interface.Results The 11 mm and 9 mm models had a poorer prosthesis stability,with the peak micromotion exceeding 50 μm and the peak internal tibial stresses of 30.75 MPa and 29.86 MPa,respectively,which exceeded the yield stress of the cancellous bone.The tibial stresses of the 7 mm and 5 mm models were within reasonable ranges and the average peak micromotions were only 42.66 μm and 40.32 μm.In contrast,the initial stability of the 5 mm model prosthesis was the best.Conclusions For total ankle replacement with Salto prosthesis,the height of the tibial component should be chosen appropriately,and the optimal height was about 5 mm.Excessive flexion and extension activities of the ankle joint should be avoided to maintain the stability of the prosthesis after surgery.This study provides a theoretical basis for the improvement of the structural parameters of the Salto prosthesis,which is valuable for the selection of clinical surgical prostheses and helps to improve the results of total ankle replacement.

Objective To investigate the biomechanical characteristics of Salto Talaris tibial components with different heights at the bone-prosthesis interface during different gait support phases after total ankle replacement.Methods An ankle joint model was reconstructed using a weight-bearing CT from a 61-year-old female patient with ankle arthritis,and Salto Talaris tibial components with different heights(5,7,9,11 mm)were modelled to simulate the loading of the tibial-prosthesis during four gait support phases,and to analyse the micromotion and stresses at the bone-prosthesis interface.Results The 11 mm and 9 mm models had a poorer prosthesis stability,with the peak micromotion exceeding 50 μm and the peak internal tibial stresses of 30.75 MPa and 29.86 MPa,respectively,which exceeded the yield stress of the cancellous bone.The tibial stresses of the 7 mm and 5 mm models were within reasonable ranges and the average peak micromotions were only 42.66 μm and 40.32 μm.In contrast,the initial stability of the 5 mm model prosthesis was the best.Conclusions For total ankle replacement with Salto prosthesis,the height of the tibial component should be chosen appropriately,and the optimal height was about 5 mm.Excessive flexion and extension activities of the ankle joint should be avoided to maintain the stability of the prosthesis after surgery.This study provides a theoretical basis for the improvement of the structural parameters of the Salto prosthesis,which is valuable for the selection of clinical surgical prostheses and helps to improve the results of total ankle replacement.

Laparoscopic total pancreatectomy (LTP) is technically challenging and infrequently documented in the literature. In this paper, we present a new approach for performing fully LTP, a pancreatic tail-first approach with a counterclockwise technique, to accomplish total mesopancreas dissection and standard lymphadenectomy en bloc. Firstly, the tail and body of the pancreas without the spleen were dissected retrogradely, starting from the lower border of the body of pancreas and then from left to right. After that, a counterclockwise dissection of the tail and body of the pancreas was performed. The splenic artery and vein were divided at the terminal end of the pancreatic tail. The spleen was preserved. The entire body and tail of the pancreas were then pulled to the right side. This maneuver facilitated the isolation and dissection of arteries in the retropancreatic region more easily via laparoscopy, including the splenic artery, gastroduodenal artery, and supporting superior mesenteric artery first-approach. It also enabled total mesopancreas dissection.The inferior pancreaticoduodenal artery was resected last during this phase. The remainder of the dissection was like that of a laparoscopic pancreaticoduodenectomy with total mesopancreas dissection, involving two laparoscopic manual anastomoses. The operative time was 490 minutes and the total blood loss was 100 mL. Pathology revealed a low-grade intraductal papillary mucinous neoplasm extending from the head to the tail of the pancreas.

Objective·To explore the effects and potential mechanisms of emodin on Alzheimer's disease(AD).Methods·Wild-type C57BL/6J mice and 3×Tg-AD mice were divided into 6 groups:Control group(C57BL/6J mice),AD group(3×Tg-AD mice),Emodin 25 mg/kg group(3×Tg-AD mice+Emodin 25 mg/kg),Emodin 50 mg/kg group(3×Tg-AD mice+Emodin 50 mg/kg),Emodin 100 mg/kg group(3×Tg-AD mice+Emodin 100 mg/kg)and Donepezil group(3×Tg-AD mice+Donepezil 3 mg/kg).The Morris water maze test was used to evaluate the learning and memory abilities of mice.The expression of glial fibrillary acidic protein(GFAP),glucose-regulated protein 78kDa(GRP78),and inositol-requiring enzyme 1α(IRE1α)was detected by immunohistochemistry.The levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and IL-6 in brain tissue were measured by enzyme-linked immunosorbent assay(ELISA).Western blotting was used to detect the expression of NF-κB p65,p-NF-κB p65,p38,and p-p38 proteins.Results·Compared with the control group,mice in the AD group showed impaired cognition,increased GFAP expression,elevated levels of TNF-α,IL-1β and IL-6,and increased expression of GRP78 and IRE1α,along with enhanced phosphorylation of NF-κB p65 and p38.Compared with the AD group,emodin improved cognitive impairment of AD mice,inhibited astrocyte overactivation and neuroinflammation,and decreased the expression of GRP78,IRE1α,phosphorylated NF-κB p65,and phosphorylated p38 in brain tissue.Conclusion·Emodin can effectively improve cognitive impairment in AD mice,which may be related to the inhibition of endoplasmic reticulum stress-mediated neuroinflammation in astrocytes.

Laparoscopic total pancreatectomy (LTP) is technically challenging and infrequently documented in the literature. In this paper, we present a new approach for performing fully LTP, a pancreatic tail-first approach with a counterclockwise technique, to accomplish total mesopancreas dissection and standard lymphadenectomy en bloc. Firstly, the tail and body of the pancreas without the spleen were dissected retrogradely, starting from the lower border of the body of pancreas and then from left to right. After that, a counterclockwise dissection of the tail and body of the pancreas was performed. The splenic artery and vein were divided at the terminal end of the pancreatic tail. The spleen was preserved. The entire body and tail of the pancreas were then pulled to the right side. This maneuver facilitated the isolation and dissection of arteries in the retropancreatic region more easily via laparoscopy, including the splenic artery, gastroduodenal artery, and supporting superior mesenteric artery first-approach. It also enabled total mesopancreas dissection.The inferior pancreaticoduodenal artery was resected last during this phase. The remainder of the dissection was like that of a laparoscopic pancreaticoduodenectomy with total mesopancreas dissection, involving two laparoscopic manual anastomoses. The operative time was 490 minutes and the total blood loss was 100 mL. Pathology revealed a low-grade intraductal papillary mucinous neoplasm extending from the head to the tail of the pancreas.

ObjectiveIn the realm of forensic science, dust is a valuable type of trace evidence with immense potential for intricate investigations. With the development of DNA sequencing technologies, there is a heightened interest among researchers in unraveling the complex tapestry of microbial communities found within dust samples. Furthermore, striking disparities in the microbial community composition have been noted among dust samples from diverse geographical regions, heralding new possibilities for geographical inference based on microbial DNA analysis. The pivotal role of microbial community data from dust in geographical inference is significant, underscoring its critical importance within the field of forensic science. This study aims to delve deeply into the nuances of fungal community composition across the urban landscapes of Beijing, Fuzhou, Kunming, and Urumqi in China. It evaluates the accuracy of biogeographic inference facilitated by the internal transcribed spacer 2 (ITS2) fungal sequencing while concurrently laying a robust foundation for the operational integration of environmental DNA into geographical inference mechanisms. MethodsITS2 region of the fungal genomes was amplified using universal primers known as 5.8S-Fun/ITS4-Fun, and the resulting DNA fragments were sequenced on the Illumina MiSeq FGx platform. Non-metric multidimensional scaling analysis (NMDS) was employed to visually represent the differences between samples, while analysis of similarities (ANOSIM) and permutational multivariate analysis of variance (PERMANOVA) were utilized to statistically evaluate the dissimilarities in community composition across samples. Furthermore, using Linear Discriminant Analysis Effect Size (LEfSe) analysis to identify and filter out species that exhibit significant differences between various cities. In addition, we leveraged SourceTracker to predict the geographic origins of the dust samples. ResultsAmong the four cities of Beijing, Fuzhou, Kunming and Urumqi, Beijing has the highest species richness. The results of species annotation showed that there were significant differences in the species composition and relative abundance of fungal communities in the four cities. NMDS analysis revealed distinct clustering patterns of samples based on their biogeographic origins in multidimensional space. Samples from the same city exhibited clear clustering, while samples from different cities showed separation along the first axis. The results from ANOSIM and PERMANOVA confirmed the significant differences in fungal community composition between the four cities, with the most pronounced distinctions observed between Fuzhou and Urumqi. Notably, the biogeographic origins of all known dust samples were successfully predicted. ConclusionSignificant differences are observed in the fungal species composition and relative abundance among the cities of Beijing, Fuzhou, Kunming, and Urumqi. Employing fungal ITS2 sequencing on dust samples from these urban areas enables accurate inference of biogeographical locations. The high feasibility of utilizing fungal community data in dust for biogeographical inferences holds particular promise in the field of forensic science.

Laparoscopic total pancreatectomy (LTP) is technically challenging and infrequently documented in the literature. In this paper, we present a new approach for performing fully LTP, a pancreatic tail-first approach with a counterclockwise technique, to accomplish total mesopancreas dissection and standard lymphadenectomy en bloc. Firstly, the tail and body of the pancreas without the spleen were dissected retrogradely, starting from the lower border of the body of pancreas and then from left to right. After that, a counterclockwise dissection of the tail and body of the pancreas was performed. The splenic artery and vein were divided at the terminal end of the pancreatic tail. The spleen was preserved. The entire body and tail of the pancreas were then pulled to the right side. This maneuver facilitated the isolation and dissection of arteries in the retropancreatic region more easily via laparoscopy, including the splenic artery, gastroduodenal artery, and supporting superior mesenteric artery first-approach. It also enabled total mesopancreas dissection.The inferior pancreaticoduodenal artery was resected last during this phase. The remainder of the dissection was like that of a laparoscopic pancreaticoduodenectomy with total mesopancreas dissection, involving two laparoscopic manual anastomoses. The operative time was 490 minutes and the total blood loss was 100 mL. Pathology revealed a low-grade intraductal papillary mucinous neoplasm extending from the head to the tail of the pancreas.

OBJECTIVE: Exposure to polycyclic aromatic hydrocarbons (PAHs) or metal(loid)s individually has been associated with neural tube defects (NTDs). However, the impacts of PAH and metal(loid) co-exposure and potential interaction effects on NTD risk remain unclear. We conducted a case-control study in China among population with a high prevalence of NTDs to investigate the combined effects of PAH and metal(loid) exposures on the risk of NTD. METHODS: Cases included 80 women who gave birth to offspring with NTDs, whereas controls were 50 women who delivered infants with no congenital malformations. We analyzed the levels of placental PAHs using gas chromatography and mass spectrometry, PAH-DNA adducts with ³²P-post-labeling method, and metal(loid)s with an inductively coupled plasma mass spectrometer. Unconditional logistic regression was employed to estimate the associations between individual exposures and NTDs. Least absolute shrinkage and selection operator (LASSO) penalized regression models were used to select a subset of exposures, while additive interaction models were used to identify interaction effects. RESULTS: In the single-exposure models, we found that eight PAHs, PAH-DNA adducts, and 28 metal(loid)s were associated with NTDs. Pyrene, selenium, molybdenum, cadmium, uranium, and rubidium were selected through LASSO regression and were statistically associated with NTDs in the multiple-exposure models. Women with high levels of pyrene and molybdenum or pyrene and selenium exhibited significantly increased risk of having offspring with NTDs, indicating that these combinations may have synergistic effects on the risk of NTDs. CONCLUSION Our findings suggest that individual PAHs and metal(loid)s, as well as their interactions, may be associated with the risk of NTDs, which warrants further investigation.
Humans ; Neural Tube Defects/chemically induced* ; Polycyclic Aromatic Hydrocarbons/adverse effects* ; Female ; Case-Control Studies ; China/epidemiology* ; Adult ; Pregnancy ; Environmental Pollutants ; Maternal Exposure/adverse effects* ; Metals/toxicity* ; Young Adult ; Risk Factors

Objective·To explore the effects and potential mechanisms of emodin on Alzheimer's disease(AD).Methods·Wild-type C57BL/6J mice and 3×Tg-AD mice were divided into 6 groups:Control group(C57BL/6J mice),AD group(3×Tg-AD mice),Emodin 25 mg/kg group(3×Tg-AD mice+Emodin 25 mg/kg),Emodin 50 mg/kg group(3×Tg-AD mice+Emodin 50 mg/kg),Emodin 100 mg/kg group(3×Tg-AD mice+Emodin 100 mg/kg)and Donepezil group(3×Tg-AD mice+Donepezil 3 mg/kg).The Morris water maze test was used to evaluate the learning and memory abilities of mice.The expression of glial fibrillary acidic protein(GFAP),glucose-regulated protein 78kDa(GRP78),and inositol-requiring enzyme 1α(IRE1α)was detected by immunohistochemistry.The levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and IL-6 in brain tissue were measured by enzyme-linked immunosorbent assay(ELISA).Western blotting was used to detect the expression of NF-κB p65,p-NF-κB p65,p38,and p-p38 proteins.Results·Compared with the control group,mice in the AD group showed impaired cognition,increased GFAP expression,elevated levels of TNF-α,IL-1β and IL-6,and increased expression of GRP78 and IRE1α,along with enhanced phosphorylation of NF-κB p65 and p38.Compared with the AD group,emodin improved cognitive impairment of AD mice,inhibited astrocyte overactivation and neuroinflammation,and decreased the expression of GRP78,IRE1α,phosphorylated NF-κB p65,and phosphorylated p38 in brain tissue.Conclusion·Emodin can effectively improve cognitive impairment in AD mice,which may be related to the inhibition of endoplasmic reticulum stress-mediated neuroinflammation in astrocytes.