Objective:To provide evidence-based recommendations for the prevention and management of lower limb ischemia in veno-arterial extracorporeal membrane oxygenation (VA-ECMO) patients during treatment according to search, evaluate, and summarize the best evidence on the prevention and management of lower limb ischemia in patients with VA-ECMO.Methods:Based on the PIPOST framework (population, intervention, professional, outcome, setting, and type of evidence), an evidence-based question was formulated. A systematic search was conducted according to the "6S" evidence pyramid model in both domestic and international databases, as well as professional association websites, for all evidence related to the prevention and management of lower limb ischemia in VA-ECMO patients (aged ≥18 years). The types of evidence included clinical decisions, guidelines, expert consensus, systematic reviews, evidence summaries, and original studies. The search was conducted from the construction of the databases to February 2024. Two researchers independently conducted a literature quality evaluation, extracted and summarized evidence from the studies that met the quality criteria.Results:A total of 13 articles were included, consisting of 3 clinical decisions, 3 guidelines, 3 expert consensus, 3 systematic reviews, and 1 randomized controlled trial. A total of 18 pieces of evidence in 7 dimensions were summarized, including risk factors of VA-ECMO lower limb ischemia, evaluation before catheterization, evaluation and monitoring during treatment, prevention of lower limb ischemia, treatment of lower limb ischemia, management of distal perfusion catheter (DPC), and monitoring after VA-ECMO weaning.Conclusion:This evidence summary provides evidence-based recommendations for the prevention and management of lower limb ischemia in VA-ECMO patients, aiming to assist clinical healthcare professionals in developing tailored strategies for the prevention and management of lower limb ischemia based on during VA-ECMO support.

Objective:To explore the correlation between hip muscle factors measured with CT imaging and recovery of independent mobility within 1 year after surgery in elderly patients with hip fractures.Methods:A prospective cohort study was conducted on the clinical data of 680 elderly patients with hip fractures admitted to Beijing Jishuitan Hospital of Capital Medical University from November 2018 to December 2019. The patients were assigned to dependent group and assistant group according to whether they regained pre-injury independent mobility within 1 year after surgery. Gender, age, body mass index, personal history, living habits, past diseases, Charlson comorbidity index, laboratory test indicators, fracture types, anesthesia types, surgical methods, rehabilitation training, time from injury to surgery, and hip muscle parameters in both groups were recorded. OsiriX software was employed in the measurement of the hip muscles to measure the muscle area and density of the gluteus maximus and gluteus medius/minimus on CT images, and the average values were calculated as hip muscle area and density. Then the variables of hip muscle area and density were converted seperately to gender-normalized Z-scores, and were divided into high-area group ( Z≥0) and low-area group ( Z<0), and high-density group ( Z≥0) and low-density group ( Z<0) respectively. Observable variables were primarily analyzed using univariate analysis between the independent group and assistant group. Those variables with statistically significant differences in the univariate analysis or would potentially affect mobility recovery according to previous researches although there were no statistical significance were included in a multivariate Logistic regression analysis. Three Logistic regression models were designed (Model 1 uncorrected, Model 2 corrected for gender, age and body mass index, Model 3 corrected for variables in Model 2 and other variables included after above-mentioned analysis) to analyze whether muscle parameters were risk factors for recovery of independent mobility. Additionally, generalized estimating equations were used for repeated measurement to analyze the correlation between hip muscle area and recovery of independent mobility after surgery. Results:Compared to the assistant group, the independent group were younger in age, with lower rate of living alone, being housebound, cognitive impairment, and Charlson comorbidity index, lower level of hemoglobin and albumin, higher rate of femoral neck fractures, lower rate of internal fixation, shorter time from injury to surgery, larger hip muscle area, and higher hip muscle density ( P<0.05 or 0.01). Multivariate Logistic regression analysis showed that, in the fully corrected Model 3, only hip muscle area remained significantly correlated with recovery of independent mobility ( P<0.05), while no significant difference was found between the high-density group and low-density group ( P>0.05). In the repeated measurement, patients in the high-area group were 1.84 times more likely to restore independent mobility than those in the low-area group ( OR=1.84, 95% CI 1.33, 2.53, P<0.01). Conclusions:Hip muscle area measured with CT imaging is closely correlated to the recovery of independent mobility within 1 year after surgery in elderly patients with hip fractures. Moreover, larger hip muscle area indicates a larger likelihood of recovery of independent mobility.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is an unmet clinical challenge due to the rapid increased occurrence but lacking approved drugs. Autophagy-related protein 16-like 1 (ATG16L1) plays an important role in the process of autophagy, which is indispensable for proper biogenesis of the autophagosome, but its role in modulating macrophage-related inflammation and metabolism during MASH has not been documented. Here, we aimed to elucidate the role of ATG16L1 in the progression of MASH. Methods: Expression analysis was performed with liver samples from human and mice. MASH models were induced in myeloid-specific Atg16l1-deficient and myeloid-specific Atg16l1-overexpressed mice by high-fat and high-cholesterol diet or methionine- and choline-deficient diet to explore the function and mechanism of macrophage ATG16L1 in MASH. Results: Macrophage-specific Atg16l1 knockout exacerbated MASH and inhibited energy expenditure, whereas macrophage-specific Atg16l1 transgenic overexpression attenuated MASH and promotes energy expenditure. Mechanistically, Atg16l1 knockout inhibited macrophage lipophagy, thereby suppressing macrophage β-oxidation and decreasing the production of 4-hydroxynonenal, which further inhibited stimulator of interferon genes(STING) carbonylation. STING palmitoylation was enhanced, STING trafficking from the endoplasmic reticulum to the Golgi was promoted, and downstream STING signaling was activated, promoting proinflammatory and profibrotic cytokines secretion, resulting in hepatic steatosis and hepatic stellate cells activation. Moreover, Atg16l1-deficiency enhanced macrophage phagosome ability but inhibited lysosome formation, engulfing mtDNA released by pyroptotic hepatocytes. Increased mtDNA promoted cGAS/STING signaling activation. Moreover, pharmacological promotion of ATG16L1 substantially blocked MASH progression. Conclusions ATG16L1 suppresses MASH progression by maintaining macrophage lipophagy, restraining liver inflammation, and may be a promising therapeutic target for MASH management.

With the advancement of synthetic biology, recombinant proteins are poised to play a significant role in medical applications. The scaled manufacturing is a pillar for the extensive application and development of recombinant proteins across various fields. In the large-scale production process of recombinant proteins, the removal and detection of endotoxins are essential to reduce their levels to safe thresholds in the final products. Currently, establishing stringent endotoxin limits for different recombinant protein products is a crucial aspect of safety assessment. This review begins by shedding light on the pathogenicity of endotoxins and discusses the methods for the removal and determination of endotoxins during the production processes of recombinant proteins. Subsequently, this review summarizes the endotoxin limits in industries such as biologics, medical devices, and human recombinant DNA products, particularly those in recombinant protein injection products. It is highlighted that regardless of whether the hosts for recombinant protein expression are bacteria or not, endotoxin testing is required for the final products of injectable recombinant proteins, and compliance with relevant industry standards is necessary. This review aims to provide a reference for the research on endotoxins in the large-scale production process of recombinant proteins.
Endotoxins/genetics* ; Recombinant Proteins/genetics* ; Humans ; Drug Contamination/prevention & control*

In line with the significant changes in disease spectrum, the wound healing discipline in China has shown a good momentum of development from budding to rapid growth. At present, improving the connotation of disciplinary development determines the speed and quality of disciplinary development in the future. The characteristics of wound diseases determine that the wound healing discipline must have the following property: standardization, integration, and translation. Here is the initial introduction on the connotation of standardization, collaboration, and translation in clinical practice of wound healing discipline. Besides, the discussions on standardization, integration, and translation in the 13 th National Conference of Wound Repair (Healing) and Tissue Regeneration were summarized. It is expected that these achievements can be reflected and improved in the construction of the wound healing discipline in China.

Periodontology is one of the important disciplines in oral clinical medicine, which covers a wide range of subjects and intersects with many basic disciplines. Under the environment of the implementation of modular teaching in Shanghai Jiao Tong University School of Medicine, the assessment method with separate propositions for the teaching and research section is still adopted. There is a mismatch between the assessment mode and the curriculum setting; the basic subject propositions are difficult to be combined with clinical cases; the knowledge point assessment is single, and the students' ability to integrate the knowledge points cannot be assessed. The development and construction of the comprehensive examination database for periodontology was based on curriculum integration, gathering the teaching backbones of various disciplines, focusing on periodontology, radiating all related disciplines, unifying the proposition outline, proposition type, proposition principle, combining with relevant knowledge points of various disciplines based on clinical cases, and tried to apply to clinical students majoring in stomatology. The use of the examination database promotes students' ability to flexibly apply theoretical knowledge to clinical case analysis, further promotes the reform of modular teaching, lays a solid foundation for future clinical work, and meanwhile provides an important basis for directions of the teaching and research section.

Objective: To investigate the antibacterial effect of a new photosensitizer, indocyanine green (ICG)-mediated photodynamic therapy, on a biofilm of Fusobacterium nucleatum (F. nucleatum) in vitro. Methods: The biocompatibility of the photosensitizer ICG was detected by CCK8. F. nucleatum (108 CFU/mL) was cultured in anaerobic conditions (80% N2, 10% H2 and 10% CO2) mixed with the photosensitizer ICG at concentrations of 0, 10, 20, 30, and 40 μg/mL and then treated with antibacterial photodynamic therapy (808 nm near infrared light with an intensity of 0.1 W/cm2 for 3 min), and a mature biofilm was formed after 2 days. The bacteriostatic effects of different concentrations of ICG on F. nucleatum biofilms were compared by colony formation unit count (CFU). The effect of ICG on the formation of F. nucleatum biofilms and biofilm metabolic activity was determined by crystal violet quantification and MTT assays. The effect of ICG on the formation of extracellular polysaccharides in F. nucleatum biofilms was determined by the phenol-sulfuric acid method. The change in the number of bacteria was observed by confocal microscopy. Results : CFU and biomass of the biofilm gradually decreased with increasing ICG concentration, and there were significant differences compared with the control group. Meanwhile, the metabolic activity of the biofilm and the production of extracellular polysaccharides also showed a significant difference between the ICG groups and the control group (P<0.01). At the same time, laser confocal microscopy showed that the number of living bacteria decreased gradually. Conclusion Antibacterial photodynamic therapy with photosensitizer ICG can effectively inhibit the formation of F. nucleatum biofilms.

Background Mitochondrial dynamin-related protein 1 (DRP1) regulates mitochondrial division and plays an important role in maintaining hepatocyte function. However, the role of DRP1 in cadmium exposure-induced maternal liver damage in pregnant mice remains unclear. Objective To investigate the role and mechanism of DRP1 in maternal liver damage induced by cadmium exposure during pregnancy. Methods This study consisted of animal experiments and cell experiments. (1) Animal experiments. Mice at 14 days of gestation were randomly divided into three groups: a control group, a low-dose cadmium group (LCd group: 2.5 mg·kg⁻¹), and a high-dose cadmium group (HCd group: 5 mg·kg⁻¹). The pregnant mice were intraperitoneally injected with cadmium chloride (CdCl₂) for 6 and 24 h in the next morning. The weights of pregnant mice, uterus, maternal liver, and fetal mice were recorded after sacrifice. Serum and liver of pregnant mice were collected, the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum were detected, and liver tissues were stained with HE to observe changes in liver function and liver tissue structure. The expressions of oxidative phosphorylation-related proteins, hypoxia inducible factor-1α (HIF-1α) and DRP1 proteins in liver of pregnant mice were detected by Western blotting. (2) Cell experiments. AML12 cells were treated with CdCl₂ (10 μmol·L⁻¹) for 0, 2, 6, 12, and 24 h. The expressions of oxidative phosphorylation-related proteins, DRP1, and hypoxia inducible factor-1α (HIF-1α) proteins were detected. AML12 cells were pretreated with DRP1 inhibitor Mdivi-1 for 1 h and then CdCl₂ (10 μmol·L⁻¹) for 12 h to detect the expression of oxidative phosphorylation-related proteins and DRP1 protein. AML12 cells were treated with Hif-1α siRNA for 48 h and CdCl₂ (10 μmol·L⁻¹) for 6 h to detect the expression of HIF-1α and DRP1 proteins. Results The results of animal experiments showed that cadmium exposure in pregnant mice had no effects on maternal liver weight and liver coefficient. However, the histomorphological changes and necrosis in hepatocytes were observed. Compared with the control group, the serum ALT and AST levels of pregnant mice in the LCd group were significantly increased after 6 h (P＜0.05), and the levels in the HCd group were significantly increased after 6 and 24 h (P＜0.05). Cadmium exposure during pregnancy significantly up-regulated HIF-1α and DRP1 expressions and down-regulated the expressions of oxidative phosphorylation-related proteins in maternal livers. In vitro cell experiments showed that the expressions of oxidative phosphorylation-related proteins was significantly decreased and HIF-1α and DRP1 protein expressions were significantly increased in the AML12 cells treated with CdCl₂ for 6 h. Mdivi-1 pretreatment significantly antagonized the inhibitory effect of cadmium on the expressions of oxidative phosphorylation-related proteins in AML12 cells, while Hif-1α siRNA pretreatment significantly antagonized the up-regulative effect of cadmium on DRP1 expression in AML12 cells. Conclusion Cadmium exposure in pregnant mice may up-regulate DRP1 expression by activating HIF-1α signaling, then inhibit oxidative phosphorylation level of hepatic cells, and ultimately lead to maternal liver damage.

【Objective】 To investigate the establishment of multi-center haemovigilance (HV) and the monitoring of adverse reactions to blood donation (ARBD), in order to provide basis for the management of blood donors. 【Methods】 The operation of HV was investigated by questionnaire. The total number of blood donations (including plateletpheresis) and ARBD cases occurred in each blood center from 2014 to 2018 were analyzed. 【Results】 Among the 24 blood centers in this survey, only nine got HV operated. The incidence of ARBD of 19 blood centers that fulfilled the questionnaire was in the range of (0.003~1.151) %. The change trend of number and incidence of ARBD cases were indeterminate. 【Conclusion】 Most blood centers did not got HV established. The incidence of ARBD varied greatly and was indeterminate. The application of HV should be further improved to strengthen ARBD management.

【Objective】 To provide reference for fine management of blood donors by classifying and analyzing different types of blood donors from domestic blood stations. 【Methods】 The resident population of 15 regions in China from 2016 to 2019 were taken as the research object, among which the blood donors were divided into three categories: age-eligible citizens, registered donors and donated donors. The average value and proportion of the three categories were calculated and statistically analyzed. 【Results】 The resident population of the 15 regions varied greatly. The mean 95% CI of the proportion of age-eligible citizens to resident population from 2016 to 2019 was (60.16%, 67.84%); registered donors to age-eligible citizens and resident population was (2.21%, 2.86%) and (1.41%, 1.79%), respectively; donated donors to registered donors, age-eligible citizens and resident population was (84.63%, 91.68%), (1.93%, 2.55%) and(1.23%, 1.59%), respectively. 【Conclusion】 There were differences in the number and proportion of different types of blood donors in different regions. The fine management of blood donors can help blood stations carry out more effective recruitment and retention strategies.