ObjectiveTo investigate the effect and mechanism of transplantation of human umbilical cord mesenchymal stem cell （hUC-MSC） with overexpression of the Numb gene in the treatment of cholestatic liver fibrosis （CLF）. MethodsThe technique of lentiviral transfection was used to induce the overexpression of the Numb gene in hUC-MSC （hUC-MSC^Numb-OE）， and hUC-MSC transfected with empty vector （hUC-MSC^OE-EV） was used as negative control. Bile duct ligation （BDL） was performed to establish a rat model of CLF， and then the rats were randomly divided into BDL group， hUC-MSC group， hUC-MSC^OE-EV group， and hUC-MSC^Numb-OE group， while a sham-operation group was also established. The rats in the intervention groups were given a single splenic injection of the corresponding cells after BDL， and samples were collected at the end of week 4. Related indicators were measured， including serum biochemistry， liver histopathology， the content of hydroxyproline （Hyp） in the liver， hepatic stellate cell activation， ductular reaction， liver regeneration， and the expression levels of key molecules in the Numb-p53 signaling axis. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the BDL group， the hUC-MSC group and the hUC-MSC^OE-EV group had significant reductions in the levels of serum biochemical parameters （aspartate aminotransferase， gamma-glutamyl transpeptidase， total bile acid， total bilirubin， and direct bilirubin）， liver fibrosis markers （the content of Hyp and the expression levels of alpha-smooth muscle actin， tumor necrosis factor-α， and transforming growth factor-beta 1）， and ductular reaction markers （the expression levels of CK7 and CK19） （all P <0.05）， and compared with the hUC-MSC^OE-EV group， the hUC-MSC^Numb-OE group had significantly greater improvements in the above indicators （all P <0.05）. In addition， compared with the hUC-MSC^OE-EV group， the hUC-MSC^Numb-OE group had significant improvements in the expression levels of liver regeneration-related markers （albumin and hepatocyte nuclear factor 4α） and the molecules associated with the Numb-p53 signaling axis （Numb， pNumb， Mdm2， and p53） （all P <0.05）. ConclusionOverexpression of the Numb gene can enhance the therapeutic effect of hUC-MSC on CLF， possibly by activating the Numb-PTB^L-p53-HNF4α axis， promoting the hepatic differentiation of hUC-MSCs and subsequently enhancing liver regeneration.

ObjectiveTo observe the effect of M1 bone marrow-derived macrophages （M1-BMDM） with Wnt5a knockdown on liver fibrosis and regeneration in a rat model of liver cirrhosis， and to investigate its gain-of-function effect compared with unmodified M1-BMDM. MethodsPrimary bone marrow-derived macrophages were isolated from rats and were polarized to M1 phenotype to construct M1-BMDM^Wnt5a-KD cells. A rat model of liver cirrhosis induced by CCl₄/2-AAF was established， and at the end of week 8， rats were randomly divided into model group， M1-BMDM group， M1-BMDM Wnt5a-knockdown empty vector group （M1-BMDM^KD-EV group）， and M1-BMDM Wnt5a-knockdown group （M1-BMDM^Wnt5a-KD group）， with 6 rats in each group. On the first day of week 9， the rats in each group were given a single injection of the corresponding cells via the caudal vein， along with an intraperitoneal injection of a CCR2 inhibitor. Six rats without any treatment were used as normal control group. Samples were collected at the end of week 12 to assess liver histopathology， serum liver function parameters， hepatic stellate cell activation， and the expression levels of mature hepatocyte markers. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the model group， all cell treatment groups had significant alleviation of liver inflammatory response and significant reductions in the activities of alanine aminotransferase and aspartate aminotransferase （AST） in serum （all P<0.01）， and the M1-BMDM^Wnt5a-KD group had a significantly lower serum level of AST than the M1-BMDM group （P<0.05）. The semi-quantitative analysis based on immunohistochemical staining showed that compared with the model group， all cell treatment groups had a significant reduction in the percentage of CD68-positive area （all P<0.05）， and compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had a significant reduction in the percentage of CD68-positive area and a significant increase in the percentage of CD163-positive area （both P<0.05）. Compared with the model group， all cell treatment groups had significant reductions in the mRNA expression levels of CD68 and tumor necrosis factor-α （all P<0.05） and the protein expression level of CD68 （all P<0.01）； compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had significant increases in the protein and mRNA expression levels of CD163 （both P<0.05）， significant reductions in the protein and mRNA expression levels of CD68 （both P<0.05）， and a significant reduction in the protein expression level of tumor necrosis factor-α （P<0.01）. Sirius Red collagen staining and alpha-smooth muscle actin （α-SMA） immunohistochemical staining showed that compared with the model group， all cell treatment groups had significant alleviation of liver collagen deposition and α-SMA-positive area， with the most significant changes in the M1-BMDM^Wnt5a-KD group， and compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had significantly smaller Sirius Red-positive area and α-SMA-positive area and a significantly lower content of hydroxyproline in liver tissue （all P<0.05）. Compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had significant reductions in the protein and mRNA expression levels of α-SMA and the mRNA expression level of COL-I and TGF-β （all P<0.05）. Compared with the model group， all cell treatment groups had a significant increase in the protein expression level of HNF-4α in liver tissue （all P<0.05）， and the M1-BMDM^Wnt5a-KD group had significantly higher protein and mRNA expression levels of HNF-4α and hepatocyte specific antigen than the M1-BMDM^KD-EV group （both P<0.05）. The M1-BMDM^Wnt5a-KD group had a significantly higher serum level of albumin than the M1-BMDM^KD-EV group （P<0.01）. Immunofluorescence co-staining showed that compared with the model group， all cell treatment groups had a significant increase in the number of cells stained positive for HNF and HNF-4α and Ki67 （all P<0.01）， and the M1-BMDM^Wnt5a-KD group had a significantly higher number of such cells than the M1-BMDM^KD-EV group （P<0.05）. ConclusionInhibition of Wnt5a expression enhances the therapeutic effect of M1-BMDM on rats with liver cirrhosis induced by CCl₄/2-AAF， which provides new ideas for enhancing the anti-cirrhotic effect of M1-BMDM through genetic modification.

Objective To investigate the expressions of IL-18,IL-18 binding protein isoform a(IL-18BPa)and IL-18Rα in blood CD4+Th1 cells of patients with allergic asthma(AA),and with allergic rhinitis and asthma syndrome(ARA),and the effects of allergens on their expressions.Methods Blood samples were collected from patients with AA,ARA and healthy control(HC)subjects.Flow cytometry was used to evaluate the actions of allergens on the expressions of IL-18,IL-18BPa and IL-18Rα in CD4+Th1 cells.Ovalbumin(OVA)-induced AA mouse models were established,and the expression level of IL-18Rα along with the influence of IL-18 on its expression in blood and lung Th1 cells was also explored by flow cytometry.Results Compared with HC,we observed increased IL-18 while decreased IL-18BPa expression in blood Th1 cells of AA and ARA patients.Moreover,allergens upregulated the expression levels of IL-18,IL-18BPa and IL-18Rα in Th1 cells of patients with AA and ARA.Additionally,intratracheal challenge with OVA plus IL-18 increased the proportions of blood and lung Th1 cells of HC and AA mice,and upregulated IL-18Rα expression on blood and lung Th1 cells of HC mice.Conclusion Allergens may be involved in the pathogenesis of airway allergic diseases by inducing the expressions of IL-18 and IL-18Rα in CD4+Th1 cells.

Objective:To evaluate the technical feasibility and perioperative safety of pyeloplasty assis-ted by the CarinaTM modular laparoscopic surgical robotic system in patients with ureteropelvic junction obstruction(UPJO).Methods:From November to December 2024,five consecutive patients diagnosed with UPJO underwent robot-assisted pyeloplasty using the CarinaTM modular laparoscopic surgical system at Peking University First Hospital.Data on patient demographics,intraoperative parameters(including docking time,console time,and estimated blood loss),perioperative outcomes,follow-up results,and surgeons' subjective evaluations of system performance were prospectively collected.Descriptive statistics were used;continuous variables were presented as median(range),and categorical variables as frequen-cy and percentage.Results:The cohort included four females and one male.All the patients successfully completed the robotic procedure without conversion to open or conventional laparoscopic surgery.The me-dian age was 32 years(24-37 years),and the median body mass index was 21.6 kg/m2(15.8-27.3 kg/m2).The median docking time was 8 min(3-12 min),and the median console time was 91 min(71-125 min).Intraoperative blood loss was uniformly 20 mL.The median postoperative drainage du-ration was 3 d(0-4 d),and the median length of hospital stay was 4 d(4-9 d).No Clavien-Dindo grade Ⅲ or higher complications occurred.All the patients had their double-J stents removed at 2 months postoperatively,and pain in the ipsilateral flank,reported preoperatively by all the five patients,was al-leviated.The subjective surgical success rate was 100％.Surgeons reported stable system performance throughout all the procedures,with no instances of mechanical arm interference or visual drift affecting surgical fluency.Conclusion:Preliminary findings indicate that pyeloplasty using the domestically deve-loped CarinaTM modular laparoscopic robotic system is technically feasible and perioperatively safe for the treatment of UPJO.

Objective:To compare the degranulation levels of basophils in peripheral blood mononuclear cell (PBMC) and granulocyte populations between healthy subjects and patients with sepsis, and to explore the underlying mechanisms. Additionally, plasma cytokine levels were measured in these volunteers.Methods:Peripheral blood samples were collected from both healthy individuals and sepsis patients. The degranulation level of basophils in sepsis patients and its potential mechanisms were examined. Plasma levels of IL-1β, IL-9, and IL-10 were detected, and Pearson correlation analysis was performed to assess the relationship between degranulated basophils in the granulocyte population and IL-9 levels.Results:Compared with healthy subjects, sepsis patients showed a reduction in basophil percentages within PBMC and granulocyte populations by 94.8% and 37.9%, respectively ( Z = -6.441, P < 0.05; Z = -2.681, P < 0.05). In contrast, both the proportion and number of degranulated basophils in the granulocyte population were increased (both P < 0.05). Plasma levels of IL-1β, IL-9, and IL-10 were significantly elevated in sepsis patients--by 80.6%, 36.7%, and 11.9-fold, respectively ( Z = -4.258, P < 0.05; Z = -3.606, P < 0.05; Z = -4.814, P < 0.05). Moreover, plasma IL-9 levels were highly correlated with both the percentage and count of degranulated basophils in the granulocyte population (both P < 0.05). GO and KEGG enrichment analyses revealed cytological changes and potential mechanisms involving basophils in the PBMC of sepsis patients. Conclusions:The decreased total count of basophils in sepsis patients may elevate the risk of secondary infection. Degranulated basophils in the granulocyte population may contribute to excessive inflammatory responses through IL-9 secretion.

To investigate the effectiveness of a self-developed intelligent medical record writing assistant in enhancing the efficiency of discharge record writing and improving the quality of discharge records, and to assess physicians' satisfaction with the assistant.

Objective To explore the differences in neck and lumbar spine injuries among different types of aircraft pilots and the correlation between body surface temperature and the severity of injury.Methods Data were collected by questionnaire surveys and medical examinations.Forty male pilots were selected as research objects,including 14 fighter pilots and 26 helicopter pilots,aged between 28 and 39 years,with a height range of 168 to 178 cm,and a total flight time of 600 to 2 000 h.Infrared thermal imaging was employed for skin temperature.A questionnaire survey was conducted for the assessment of the common site and degree of pain.The relationship between body surface temperature and pain was investigated.Results Fighter pilots mainly complained of discomfort in the neck and scapular region,while helicopter pilots were more likely to experience lower back pain.The skin temperature in the affected regions was significantly higher than that in the surrounding normal regions in both fighter pilots and helicopter pilots(P<0.05).The pain score was positively related with elevated temperature in the affected areas(P<0.05).Conclusion It is found that fighter pilots are more prone to neck and scapular pain,while helicopter pilots are more likely to experience lower back pain.The severity of pain is positively related with increased temperature in the affected areas.Infrared thermal imaging can be used to assess temperature variation at injured sites and the location of training injuries among pilots.

Antibiotic adjuvants offer a promising strategy for restoring antibiotic sensitivity, expanding antibacterial spectra, and reducing required dosages. Previously, compound 15 was identified as a potential adjuvant for Polymyxin B (PB) against multidrug-resistant (MDR) Pseudomonas aeruginosa DK2; however, its clinical utility was hindered by high cytotoxicity, uncertain in vivo efficacy, and an unclear synergetic mechanism. To address these challenges, we synthesized and evaluated a series of novel benzamide derivatives, with A22 emerging as a particularly promising candidate. A22 demonstrated potent synergistic activity to PB, minimal cytotoxicity, improved water solubility, and broad-spectrum synergism of polymyxins against various clinically isolated MDR Gram-negative strains. In vivo studies using Caenorhabditis elegans and mouse models further confirmed the efficacy of A22. Moreover, A22 effectively suppressed the development of PB resistance in Pseudomonas aeruginosa DK2. Mechanistic investigations revealed that A22 enhances polymyxins activity by inducing reactive oxygen species production, reducing ATP levels, increasing NOX activity, and inhibiting biofilm formation, leading to bacterial death. These findings position A22 as a highly promising candidate for the development of polymyxin adjuvants, offering a robust approach to combating MDR Gram-negative bacterial infections.

Persistent and maladaptive drug-related memories represent a key component in drug addiction. Converging evidence from both preclinical and clinical studies has demonstrated the potential efficacy of the memory reconsolidation updating procedure (MRUP), a non-pharmacological strategy intertwining two distinct memory processes: reconsolidation and extinction-alternatively termed "the memory retrieval-extinction procedure". This procedure presents a promising approach to attenuate, if not erase, entrenched drug memories and prevent relapse. The present review delineates the applications, molecular underpinnings, and operational boundaries of MRUP in the context of various forms of substance dependence. Furthermore, we critically examine the methodological limitations of MRUP, postulating potential refinement to optimize its therapeutic efficacy. In addition, we also look at the potential integration of MRUP and neurostimulation treatments in the domain of substance addiction. Overall, existing studies underscore the significant potential of MRUP, suggesting that interventions predicated on it could herald a promising avenue to enhance clinical outcomes in substance addiction therapy.
Humans ; Substance-Related Disorders/psychology* ; Memory Consolidation/physiology* ; Animals ; Extinction, Psychological/physiology*

Flexible conductive fibers have been widely applied in wearable flexible sensing. However, exposed wearable flexible sensors based on liquid metal (LM) are prone to abrasion and significant conductivity degradation. This study presented a high-sensitivity LM conductive fiber with integration of strain sensing, electrical heating, and thermochromic capabilities, which was fabricated by coating eutectic gallium-indium (EGaIn) onto spandex fibers modified with waterborne polyurethane (WPU), followed by thermal curing to form a protective polyurethane sheath. This fiber, designated as Spandex/WPU/EGaIn/Polyurethane (SWEP), exhibits a four-layer coaxial structure: spandex core, WPU modification layer, LM conductive layer, and polyurethane protective sheath. The SWEP fiber had a diameter of (458.3 ± 10.4) μm, linear density of (2.37 ± 0.15) g/m, and uniform EGaIn coating. The fiber had excellent conductivity with an average value of (3 716.9 ± 594.2) S/m. The strain sensing performance was particularly noteworthy. A 5 cm × 5 cm woven fabric was fabricated using polyester warp yarns and SWEP weft yarns. The fabric exhibited satisfactory moisture permeability [(536.06 ± 33.15) g/(m ²·h)] and maintained stable thermochromic performance after repeated heating cycles. This advanced conductive fiber development is expected to significantly promote LM applications in wearable electronics and smart textile systems.
Wearable Electronic Devices ; Polyurethanes/chemistry* ; Electric Conductivity ; Gallium/chemistry* ; Metals/chemistry*