Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with postsymptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over 9 years. The most common adverse events (AEs) within 2 months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with postsymptomatic juvenile MLD.
Humans ; Leukodystrophy, Metachromatic/genetics* ; Pilot Projects ; Genetic Therapy/methods* ; Hematopoietic Stem Cell Transplantation ; Male ; Follow-Up Studies ; Female ; Lentivirus/genetics* ; Child ; Child, Preschool ; Hematopoietic Stem Cells/metabolism* ; Cerebroside-Sulfatase/metabolism* ; Adolescent

OBJECTIVES: To identify risk factors contributing to prolonged postoperative length of stay (LOS) in very elderly patients following hip fracture surgery, with a focus on postoperative complications and the impact of different anesthesia approaches. METHODS: This retrospective single-center cohort study enrolled patients aged 90 years or older who underwent hip fracture surgery at Peking Union Medical College Hospital between January 31, 2013 and December 31, 2023. Relevant perioperative data were collected. The primary outcome was postoperative LOS, and the study cohort was divided into two groups: postoperative LOS ≤ 7 days and LOS > 7 days. Logistic regression was performed to identify factors related to prolonged postoperative LOS. RESULTS: A total of 155 patients were included. The average age was 92.7 ± 2.6 years. There were 73 (47%) patients with postoperative LOS > 7 days. Postoperative pneumonia was the only factor associated with a prolonged postoperative LOS (OR = 2.12, 95% CI [1.09, 4.16], P = 0.028). Neither the type of anesthesia (regional vs. general anesthesia, OR = 1.00, 95% CI [0.53, 1.90], P = 0.993) nor the method of airway management (laryngeal mask ventilation vs. spontaneous breathing, OR = 1.46, 95% CI [0.58, 3.76], P = 0.424; endotracheal intubation vs. spontaneous breathing, OR = 0.82, 95% CI [0.39, 1.69], P = 0.592) showed a significant association with a prolonged postoperative LOS. Preoperative chronic obstructive pulmonary disease (OR = 2.78, 95% CI [1.05, 7.65], P = 0.040) and preoperative neutrophil count (OR = 1.13, 95% CI [1.01, 1.26], P = 0.029) were both significantly associated with the occurrence of postoperative pneumonia, while anesthesia type and airway management method were not. CONCLUSIONS Postoperative pneumonia was associated with prolonged postoperative LOS in very elderly patients undergoing hip fracture surgery, whereas anesthesia types and airway management methods show no association with prolonged postoperative LOS or postoperative pneumonia. Preoperative comorbidities, especially respiratory conditions and systemic inflammation, potentially play a substantial role in postoperative recovery.
Humans ; Hip Fractures/surgery* ; Aged, 80 and over ; Risk Factors ; Length of Stay ; Female ; Male ; Retrospective Studies ; Postoperative Complications/etiology*

The medical mask,which is used as an important tool of preventing the spread of respiratory diseases,can effectively block the transmission of biological aerosols.The detection for the filtration efficiency of bacteria in medical mask is particular importance.The Andersen sampler,is one kind of device that samples microbial aerosols,is widely used in the inspection for the filtration efficiency for bacteria in medical masks.It mainly consists of six impactors with different pore sizes.It simulates the deposition process of the most of particles at different positions in respiratory system through the bacterial particles in biological aerosols impact respectively the surface of petri dishes with agar under different pore sizes.This paper explored the development background,structure and sampling principle,operation and counting procedures of the Andersen sampler,as well as its application and importance in the inspection for the filtration efficiency for bacteria in medical mask.

Objective To investigate the impacts of epidural anesthesia with ropivacaine combined with dezocine on lower limb motor nerve block and maternal and infant outcomes in primipara undergoing painless delivery.Methods A total of 159 primiparas who delivered in Nanjing Jiangbei Hospital were selected as the research objects,and divided into the blank group(53 cases),the ropivacaine group(53 cases)and the combined group(53 cases)by the random number table method.Parturients in the blank group were given natural delivery mode,parturients in the ropivacaine group were given ropivacaine epidural anesthesia,and parturients in the combined group were given dezocine anesthesia on the basis of ropivacaine.Analgesic effect at different time points,time of the first,second and third stage of labor,pressing times of analgesic pump,lower limbs motor nerve block,maternal and infant outcomes,and adverse reactions of parturients were compared among the three groups.Results At 10 minutes after analgesia,60 minutes after analgesia,when the cervix was fully dilated and when the fetus was delivered,the VAS scores of the parturients in the ropivacaine group and the combined group were lower than those in the blank group(P<0.05),and the VAS scores of the parturients in the combined group were significantly lower than those in the ropivacaine group(P<0.05).There was no significant difference in the time of the first,second or third stage of labor of parturients among the three groups(P>0.05);The pressing times of analgesic pump of parturients in the combined group was significantly less than that in the ropivacaine group(P<0.05).There was no statistically significant difference in terms of low limb motor nerve block after painless labor of parturients among the three groups(P>0.05).There were no statistically significant differences in the perineal incision rate or the Apgar scores of newborns at 1 minute and 5 minutes after birth among the three groups(P>0.05).The usage rate of forceps and the rate of conversion to cesarean section in the combined group were significantly lower than those in the ropivacaine group and the blank group(P<0.05).There was no statistically significant difference in the incidence of total adverse reactions among the blank group,the ropivacaine group and the combined group(P>0.05).Conclusion The combination of ropivacaine and dezocine for epidural anesthesia has a better analgesic effect on primiparas with painless delivery,has a smaller impact on lower limb motor nerve block in parturients,and can achieve better maternal and infant outcomes.

Objective To investigate the impacts of epidural anesthesia with ropivacaine combined with dezocine on lower limb motor nerve block and maternal and infant outcomes in primipara undergoing painless delivery.Methods A total of 159 primiparas who delivered in Nanjing Jiangbei Hospital were selected as the research objects,and divided into the blank group(53 cases),the ropivacaine group(53 cases)and the combined group(53 cases)by the random number table method.Parturients in the blank group were given natural delivery mode,parturients in the ropivacaine group were given ropivacaine epidural anesthesia,and parturients in the combined group were given dezocine anesthesia on the basis of ropivacaine.Analgesic effect at different time points,time of the first,second and third stage of labor,pressing times of analgesic pump,lower limbs motor nerve block,maternal and infant outcomes,and adverse reactions of parturients were compared among the three groups.Results At 10 minutes after analgesia,60 minutes after analgesia,when the cervix was fully dilated and when the fetus was delivered,the VAS scores of the parturients in the ropivacaine group and the combined group were lower than those in the blank group(P<0.05),and the VAS scores of the parturients in the combined group were significantly lower than those in the ropivacaine group(P<0.05).There was no significant difference in the time of the first,second or third stage of labor of parturients among the three groups(P>0.05);The pressing times of analgesic pump of parturients in the combined group was significantly less than that in the ropivacaine group(P<0.05).There was no statistically significant difference in terms of low limb motor nerve block after painless labor of parturients among the three groups(P>0.05).There were no statistically significant differences in the perineal incision rate or the Apgar scores of newborns at 1 minute and 5 minutes after birth among the three groups(P>0.05).The usage rate of forceps and the rate of conversion to cesarean section in the combined group were significantly lower than those in the ropivacaine group and the blank group(P<0.05).There was no statistically significant difference in the incidence of total adverse reactions among the blank group,the ropivacaine group and the combined group(P>0.05).Conclusion The combination of ropivacaine and dezocine for epidural anesthesia has a better analgesic effect on primiparas with painless delivery,has a smaller impact on lower limb motor nerve block in parturients,and can achieve better maternal and infant outcomes.

Objective:To investigate the effect of LINC00641 on the viability and apoptosis of acute myeloid leukemia(AML)cells and its mechanism.Methods:RT-qPCR was applied to detect the relative expression levels of LINC00641,miR-204-5p,and MT1X in human normal bone marrow stromal cell lines HS-5 and AML cell lines,and to screen the optimal cell line THP-1 was screened for subsequent experiments.Bioinformatics,dual luciferase reporter assay,pull down assay,and RIP assay were applied to validate the targeting relationship between LINC00641,MT1X and miR-204-5p.EdU,CCK-8,flow cytometry,and Transwell assay were applied to detect cell proliferation,apoptosis,migration and invasion,respectively.Western blot was applied to detect the expression of MT1X,CyclinD1,Bcl-2,and Bax proteins.Results:Compared with HS-5 cells,the expression of LINC00641 and MT1X was obviously increased in HL60,THP-1,U937,and KG1 cells,while the expression of miR-204-5p was obviously reduced(all P＜0.05).THP-1 cells showed the most obvious changes(P＜0.05).Silencing LINC00641 or overexpressing miR-204-5p was able to obviously inhibit the proliferation,migration and invasion of THP-1 cells,as well as the expression of CyclinD1 and Bcl-2 proteins,while promote cells apoptosis and Bax protein expression(all P＜0.05).Bioinformatics analysis,dual luciferase reporter assay,pull down assay,and RIP assay all confirmed that there were targeted relationships between LINC00641,MT1X and miR-204-5p.Inhibiting miR-204-5p or overexpressing MT1X was able to respectively reverse the inhibitory effect of silencing LINC00641 or overexpressing miR-204-5p on THP-1 cells proliferation,migration and invasion,and reduce cells apoptosis.Conclusion:LINC00641 is highly expressed in AML,and inhibition of LINC00641 expression can inhibit cell proliferation,migration,and invasion and increase apoptosis by regulating the miR-204-5p/MT1X axis.

The medical mask,which is used as an important tool of preventing the spread of respiratory diseases,can effectively block the transmission of biological aerosols.The detection for the filtration efficiency of bacteria in medical mask is particular importance.The Andersen sampler,is one kind of device that samples microbial aerosols,is widely used in the inspection for the filtration efficiency for bacteria in medical masks.It mainly consists of six impactors with different pore sizes.It simulates the deposition process of the most of particles at different positions in respiratory system through the bacterial particles in biological aerosols impact respectively the surface of petri dishes with agar under different pore sizes.This paper explored the development background,structure and sampling principle,operation and counting procedures of the Andersen sampler,as well as its application and importance in the inspection for the filtration efficiency for bacteria in medical mask.

The breakage pattern of unit particles during the production of oral solid dosage forms (OSD) is closely related to the quality of intermediate or final products. To accurately characterize the particles and study the evolution law of particle breakage, the Bonding model of the discrete element method (DEM) was used to investigate the breakage patterns of model parameters, particle shape and process conditions (loading mode and loading rate) on the dynamic breakage, force-time curve, breakage rate, maximum breakage size ratio and fracture strength of particles. The results showed that the particle breakage force was positively correlated with normal strength and bonded disk scale, negatively correlated with normal stiffness per unit area and tangential stiffness per unit area, and weakly correlated with tangential strength. The particle breakage rate was negatively correlated with the aspect ratio of the particles, and the maximum breakage size ratio was positively correlated with the aspect ratio of the particles; among the three loading modes, the breakage rate of compression breakage model was the largest, the breakage rate of shear breakage model was the second largest, and the breakage rate of wear breakage model was the smallest; the maximum breakage size ratio was positively correlated with the loading rate, the loading mode and the loading rate had no mutual influence on particle breakage rate, but had mutual influence on the maximum breakage size ratio. The research results will provide a theoretical basis for the shift of OSD from batch manufacturing to advanced manufacturing.

Objective:To explore the levels of regulatory T cells(Tregs)and cytokines IL-35,TGF-β and IL-10 in peripheral blood of hemophilia A(HA)patients with F Ⅷ inhibitor and their clinical significance.Methods:43 HA patients admitted to the Hematology Department of the Affiliated Hospital of North China University of Science and Technology from October 2019 to December 2020 were selected,including 6 cases with F Ⅷ inhibitor and 37 cases without FⅧ inhibitor.In addition,20 healthy males who underwent physical examinations were selected as healthy controls.Flow cytometry was used to detect the levels of CD4+CD25+CD127-Tregs in peripheral blood of the HA patients and healthy controls,and ELISA assay was used to detect the expression levels of IL-35,TGF-β and IL-10 in serum,and their differences between different groups were compared.Results:Compared with the healthy control group,the level of Tregs in HA patients was decreased,and the level of Tregs in the FⅧ inhibitor positive group was the lowest,the difference was statistically significant(P＜0.05).There was no significant difference in the expression level of Tregs in HA patients of different severity levels.The serum IL-35,TGF-β,and IL-10 levels in both FⅧ inhibitor negative and positive groups were significantly lower than those in healthy control group,and those in FⅧ inhibitor positive group were significantly lower than those in FⅧ inhibitor negative group(all P＜0.05).Conclusion:The decrease of Tregs,IL-35,TGF-β,and IL-10 levels in HA patients may be related to the formation of FⅧ inhibitors.

Background::In vitro fertilization (IVF) has emerged as a transformative solution for infertility. However, achieving favorable live-birth outcomes remains challenging. Current clinical IVF practices in IVF involve the collection of heterogeneous embryo data through diverse methods, including static images and temporal videos. However, traditional embryo selection methods, primarily reliant on visual inspection of morphology, exhibit variability and are contingent on the experience of practitioners. Therefore, an automated system that can evaluate heterogeneous embryo data to predict the final outcomes of live births is highly desirable. Methods::We employed artificial intelligence (AI) for embryo morphological grading, blastocyst embryo selection, aneuploidy prediction, and final live-birth outcome prediction. We developed and validated the AI models using multitask learning for embryo morphological assessment, including pronucleus type on day 1 and the number of blastomeres, asymmetry, and fragmentation of blastomeres on day 3, using 19,201 embryo photographs from 8271 patients. A neural network was trained on embryo and clinical metadata to identify good-quality embryos for implantation on day 3 or day 5, and predict live-birth outcomes. Additionally, a 3D convolutional neural network was trained on 418 time-lapse videos of preimplantation genetic testing (PGT)-based ploidy outcomes for the prediction of aneuploidy and consequent live-birth outcomes.Results::These two approaches enabled us to automatically assess the implantation potential. By combining embryo and maternal metrics in an ensemble AI model, we evaluated live-birth outcomes in a prospective cohort that achieved higher accuracy than experienced embryologists (46.1% vs. 30.7% on day 3, 55.0% vs. 40.7% on day 5). Our results demonstrate the potential for AI-based selection of embryos based on characteristics beyond the observational abilities of human clinicians (area under the curve: 0.769, 95% confidence interval: 0.709–0.820). These findings could potentially provide a noninvasive, high-throughput, and low-cost screening tool to facilitate embryo selection and achieve better outcomes. Conclusions::Our study underscores the AI model’s ability to provide interpretable evidence for clinicians in assisted reproduction, highlighting its potential as a noninvasive, efficient, and cost-effective tool for improved embryo selection and enhanced IVF outcomes. The convergence of cutting-edge technology and reproductive medicine has opened new avenues for addressing infertility challenges and optimizing IVF success rates.