OBJECTIVE To understand the drug resistance genes,virulence genes and molecular epidemiological characteristics of extensively drug-resistant hypervirulent Klebsiella pneumoniae(XDR-hvKP)strains causing hospital-associated infection.METHODS The clinical isolates of XDR-hvKP were collected from Tongling People's Hospital from Jul.2020 to Dec.2022.The strains were identified by matrix-assisted laser desorption ionization-time-of-flight(MALDI-TOF)mass spectrometry,the common drug resistance genes and virulence genes were an-alyzed by Sanger sequencing,the capsular serotypes were determined by wzi gene sequencing;the drug resistance genes,virulence genes and ST subtypes were observed by means of whole-genome sequencing(WGS)technique.RESULTS Totally 18 strains of XDR-hvKP were collected,55.56％(10/18)of which were isolated from blood specimens,and 61.11％(11/18)were isolated from critical care medicine department.Sanger sequen-cing analysis showed that all of the strains carried blaKPC-2 drug resistance gene;rmpA2(100.00％)and rmpA,i-roN,iutA(94.44％,17/18)were the major virulence genes carried by the strains.WGS analysis indicated that all of the 18 XDR-hvKP isolates carried multiple drug resistance genes such as blaKPC-2 carbapenemase and the viru-lence genes like capsule(rmpA/rmpA2),aerobacterin(iucABCD-iutA),Salmonella(iroN)and yersinin(ybt).All of the ST subtypes were ST 11,and all of the capsular serotypes were KL 64.CONCLUSIONS The ST11-KL64 type XDR-hvKP strains carry blaKPC-2;rmpA,rmpA2,iroN and iutA are the major virulence genes.It is necessary to strengthen the monitoring of key population of the key departments and make joint efforts of multiple departments to contain the transmission of the strains.

Recent studies have shown that the physiological homeostasis of oral mucosal cells is regulated by the circadian clock.Dis-ruption or dysfunction of the circadian clock is closely associated with the development of oral squamous cell carcinoma(OSCC).Research based on the circadian clock offers a novel perspective on the pathogenesis and therapeutic strategies for OSCC.However,there is current-ly limited research on this topic,and people generally have insufficient understanding and recognition of the circadian clock.Given the complexity and challenges of circadian clock which is the fourth dimension of medical research,we organize relevant experts based on summarizing the current research results of circadian clock in the pathogenesis and precision diagnosis and treatment of OSCC,combining the scientific principles of the circadian clock's role and their long-term research experience,then summarizes and recommends the con-sensus opinions for the research of circadian clock in the pathogenesis mechanism and precision diagnosis and treatment of human OSCC,with the hope of providing guidance for the basic research and clinical application of circadian clock or circadian rhythm in the pathogene-sis mechanism and precision diagnosis and treatment of oral and maxillofacial squamous cell carcinoma.

OBJECTIVE To understand the drug resistance genes,virulence genes and molecular epidemiological characteristics of extensively drug-resistant hypervirulent Klebsiella pneumoniae(XDR-hvKP)strains causing hospital-associated infection.METHODS The clinical isolates of XDR-hvKP were collected from Tongling People's Hospital from Jul.2020 to Dec.2022.The strains were identified by matrix-assisted laser desorption ionization-time-of-flight(MALDI-TOF)mass spectrometry,the common drug resistance genes and virulence genes were an-alyzed by Sanger sequencing,the capsular serotypes were determined by wzi gene sequencing;the drug resistance genes,virulence genes and ST subtypes were observed by means of whole-genome sequencing(WGS)technique.RESULTS Totally 18 strains of XDR-hvKP were collected,55.56％(10/18)of which were isolated from blood specimens,and 61.11％(11/18)were isolated from critical care medicine department.Sanger sequen-cing analysis showed that all of the strains carried blaKPC-2 drug resistance gene;rmpA2(100.00％)and rmpA,i-roN,iutA(94.44％,17/18)were the major virulence genes carried by the strains.WGS analysis indicated that all of the 18 XDR-hvKP isolates carried multiple drug resistance genes such as blaKPC-2 carbapenemase and the viru-lence genes like capsule(rmpA/rmpA2),aerobacterin(iucABCD-iutA),Salmonella(iroN)and yersinin(ybt).All of the ST subtypes were ST 11,and all of the capsular serotypes were KL 64.CONCLUSIONS The ST11-KL64 type XDR-hvKP strains carry blaKPC-2;rmpA,rmpA2,iroN and iutA are the major virulence genes.It is necessary to strengthen the monitoring of key population of the key departments and make joint efforts of multiple departments to contain the transmission of the strains.

Magnetic stimulation has made significant strides in the treatment of psychiatric disorders. Nonetheless, current magnetic stimulation techniques lack the precision to accurately modulate specific nuclei and cannot realize deep brain magnetic stimulation. To address this, we utilized superparamagnetic iron oxide nanoparticles as mediators to achieve precise targeting and penetration. We investigated the effects of magnetic fields with varying frequencies on neuronal activity and compared the activation effects on neurons using a 10-Hz precise magneto-stimulation system (pMSS) with repetitive transcranial magnetic stimulation in mice. Oxytocin levels, dendritic morphology and density, and mouse behavior were measured before and after pMSS intervention. Our findings suggest that pMSS can activate oxytocinergic neurons, leading to upregulation of oxytocin secretion and neurite outgrowth. As a result, sociability was rapidly improved after a one-week pMSS treatment regimen. These results demonstrate a promising magneto-stimulation method for regulating neuronal activity in deep brain nuclei and provide a promising therapeutic approach for autism spectrum disorder.
Animals ; Autism Spectrum Disorder/physiopathology* ; Paraventricular Hypothalamic Nucleus/physiology* ; Disease Models, Animal ; Transcranial Magnetic Stimulation/methods* ; Male ; Social Behavior ; Mice ; Oxytocin/metabolism* ; Mice, Inbred C57BL ; Neurons/physiology*

Pelvic organ prolapse (POP), whose etiology is influenced by genetic and clinical risk factors, considerably impacts women's quality of life. However, the genetic underpinnings in non-European populations and comprehensive risk models integrating genetic and clinical factors remain underexplored. This study constructed the first polygenic risk score (PRS) for POP in the Chinese population by utilizing 20 disease-associated variants from the largest existing genome-wide association study. We analyzed a discovery cohort of 576 cases and 623 controls and a validation cohort of 264 cases and 200 controls. Results showed that the case group exhibited a significantly higher PRS than the control group. Moreover, the odds ratio of the top 10% risk group was 2.6 times higher than that of the bottom 10%. A high PRS was significantly correlated with POP occurrence in women older than 50 years old and in those with one or no childbirths. As far as we know, the integrated prediction model, which combined PRS and clinical risk factors, demonstrated better predictive accuracy than other existing PRS models. This combined risk assessment model serves as a robust tool for POP risk prediction and stratification, thereby offering insights into individualized preventive measures and treatment strategies in future clinical practice.
Humans ; Female ; Pelvic Organ Prolapse/epidemiology* ; Middle Aged ; Risk Assessment/methods* ; China/epidemiology* ; Multifactorial Inheritance ; Aged ; Risk Factors ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; Case-Control Studies ; Adult ; Polymorphism, Single Nucleotide ; Genetic Risk Score ; East Asian People

Objective: To compare quality control (relative purity and specific activity) and process control [plasminogen (Pg) antigen recovery and potency recovery] indexes of samples before and after adding the Q chromatography step to the full chromatography process of human Pg, thereby determining whether the addition of this step could improve Pg recovery by affinity chromatography. Methods: A Q chromatography step was added before the Pg affinity chromatography in the original Pg chromatography process. The loading solution, flow through solution and eluate of Q chromatography and Pg affinity chromatography were collected. The potency of coagulation factor Ⅱ (FⅡ), Ⅶ (FⅦ), Ⅷ (FⅧ), Ⅸ (FⅨ), and Ⅹ(FⅩ) were detected by the coagulation method, the total protein content was detected by the BCA method, and the Pg potency was detected by the chromogenic substrate method. The content of specific plasma proteins was detected by immunoturbidimetry, the potency recovery of coagulation factors was calculated, and the flow direction of coagulation factors was analyzed. The recovery of different plasma protein antigens were calculated, and the distribution of impurity proteins was analyzed. The relative purity and specific activity of Pg, antigen content, and potency recovery in the target fractions were calculated and compared with the original process indicators, so as to determine the effect of adding Q chromatography on the original process. Furthermore, the reproducibility after process modification was assessed. Results: 100% of FⅡ, FⅩ, and FⅨ, 87.81% of FⅧ, and 40.44% of FⅦ in filtered plasma were removed by Q chromatography. The residual FⅦ (53.26%) and FⅧ (13.30%) in Q flow-through fraction were completely removed by Pg affinity chromatography. In both the original process (without Q-chromatography) and the modified process (with Q-chromatography), non-target plasma proteins mainly existed in the flow-through fraction of Pg affinity chromatography. The antigen recovery of IgM, ceruloplasmin (CER), and fibronectin (FNC) in Q-chromatography flow-through fraction were reduced. In contrast, antigen recovery of other plasma proteins [IgG, IgA, Pg, albumin (AlB), alpha-1-antitrypsin (AAT), and fibrinogen (Fg)] were all >90%, which were consistent with the protein composition and proportion in the original affinity chromatography loading solution. Compared with the recovery rate of Pg antigen in the original process (74.4%), the total recovery of Pg antigen in the modified process was significantly increased (89.97%). Compared with the recovery of IgG (97.48%) and Fg (95.32%) in the Pg affinity flows-through fraction of the original process, the modified process resulted in a slight reduction in the recovery of IgG (94.60%), while the recovery of Fg was not affected (95.05%). The potency recovery rate, specific activity, and relative purity of Pg after Q chromatography were 99.3%, 0.016 U/mg, and 0.15%. These values were the same as those of Pg affinity chromatography loading solution by the original process, indicating that introduction of Q chromatography did not affect subsequent Pg affinity chromatography. Compared with the recovery of Pg antigen in three batches of the original process (66.49±1.02)%, the recovery of Pg antigen in the affinity chromatography eluent of the modified process [five batches; (77.43±4.43)%] was significantly improved. Furthermore, the potency recovery was (86.80±4.28)%, the relative purity was (81.99±1.25)%, the specific activity was (8.679±1.073)U/mg, and the process was reproducible. Conclusion: The addition of Q chromatography could improve the recovery of Pg affinity chromatography in the full chromatography process.

Objective:To explore the morphological characteristics of the corpus callosum (CC) in patients with unilateral medial temporal lobe epilepsy (mTLE) with hippocampal sclerosis (HS), and their correlation with hippocampal volume and clinical indicators.Methods:This was a cross-sectional study. Clinical (age of onset, disease duration, seizure frequency, seizure duration, etc.) and imaging data of 44 patients mTLE with unilateral HS confirmed by postoperative pathology and 42 healthy controls (HCs) recruited at West China Hospital of Sichuan University from June 2017 to May 2023 were analyzed retrospectively. Among the 44 patients, 19 had left-sided HS and 25 had right-sided HS. All subjects underwent high-resolution 3D T 1WI. Hippocampal volumes were obtained using FreeSurfer. ART was used to measure the morphological parameters of the CC for each participant, including total CC area, volume, perimeter, length, thickness, circularity, and the area of seven CC subregions defined by Witelson: rostrum, genu, body, anterior midbody, posterior midbody, isthmus and splenium. Differences in these metrics between two or three groups were compared using independent samples t-test or one-way ANOVA. Pearson or Spearman correlation analysis was used to observe the correlation between morphological features of the CC and hippocampal volume and other clinical indicators in patients with mTLE with unilateral HS. Results:Compared with HCs, patients with mTLE with unilateral HS had significantly reduced total CC area, CC circularity, as well as the area and thickness of the genu, anterior midbody, posterior midbody, isthmus, splenium, and the area of the rostrum ( P<0.05). Significant differences were observed in the total area, circularity, and subregional areas (genu, rostrum, anterior midbody, posterior midbody, splenium), as well as thickness (genu, anterior midbody, posterior midbody, isthmus) of the CC among mTLE with left-sided HS, mTLE with right-sided HS, and HCs ( P<0.05). When compared to HCs, the total area of the CC, circularity and the areas of the genu, rostrum, anterior midbody, posterior midbody, and splenium, and the thicknesses of the genu, anterior midbody, posterior midbody, and isthmus of the CC were significantly reduced in patients with mTLE with right-sided HS ( P<0.05), and the thicknesses of the midbody and isthmus of the CC were significantly reduced in patients with mTLE with left-sided HS compared to HCs ( P<0.05), and the two-by-two comparison of the rest of the indicators did not show statistically significant differences ( P>0.05). Correlation analysis showed that some morphological abnormalities in the CC in mTLE with unilateral HS patients were significantly correlated with age of onset, disease duration, seizure frequency, seizure duration, and hippocampal volume. Conclusions:mTLE with unilateral HS patients can exhibit morphological abnormalities in the CC, particularly in those with right-sided lesions. These abnormalities are significantly associated with seizure-related factors and hippocampal atrophy.

Objective:To analyze the efficacy of endovascular treatment for venous outflow tract obstruction after liver transplantation.Methods:A retrospective analysis was conducted on the data of 7 patients with venous outflow tract obstruction after liver transplantation admitted to Beijing Friendship Hospital, Capital Medical University from November 2020 to December 2024. Among them, there were 5 males and 2 females, with the age of (22.3±8.1) years. The primary diseases included 2 cases of Budd-Chiari syndrome, 1 case of hepatic veno-occlusive disease, 1 case of portal veno-hepatic sinus vascular disease, 1 case of ornithine carbamoyltransferase deficiency, 1 case of primary biliary cirrhosis, and 1 case of autoimmune cirrhosis. Analyze the patient's clinical manifestations, obstruction of venous outflow tract, hemoglobin levels within one week before and one week after the operation, endovascular treatment conditions, and intraoperative complications such as abdominal hemorrhage and vascular injury. Ultrasound was used to measure the depth of ascites and pleural effusion. All patients were followed up immediately after the operation through phone calls or follow-up visits. The clinical symptoms, abdominal vascular ultrasound, enhanced CT and survival status of the patients were followed up.Results:All 7 patients were diagnosed with venous outflow tract obstruction by intraoperative angiography, including 1 cases of inferior vena cava obstruction, 2 cases of hepatic vein obstruction, and 4 cases of vena cava combined with hepatic vein obstruction. A total of 12 endovascular treatments were performed on 7 patients. Among them, 4 patients received balloon dilation and angioplasty once, 1 patient received balloon dilation and angioplasty twice, 1 patient underwent hepatic vein stent implantation after 2 hepatic vein balloon dilation and angioplasty, and 1 patient underwent intrahepatic portosystemic shunt via jugular vein after 2 hepatic vein balloon dilation and angioplasty. The abdominal distensionof the patients were all relieved after the operation, the ascites and pleural effusion decreased, and the edema symptoms of the lower extremities disappeared. There were no intraoperative complications. The preoperative hemoglobin of 7 patients was (113.4±34.0) g/L, and the postoperative hemoglobin was (126.6±34.8) g/L, which increased significantly compared with that before the operation, and the difference was statistically significant ( t=-0.71, P=0.038). Seven patients were followed up for 6 to 24 months, with a median of 12 months. None of them had obvious symptoms including abdominal distension. Abdominal ultrasound and CT indicated that the blood flow of the transplanted liver was unobstructed, and no patient died. Conclusion:Venous outflow tract obstruction after liver transplantation can cause severe symptoms. Endovascular treatment is an effective treatment for venous outflow tract obstruction after liver transplantation.

Objective:To explore the molecular mechanism by which interferon regulatory factor 1 (IRF1) affects hepatic ischemia-reperfusion injury (HIRI) by regulating the polarization of Kupffer cells.Methods:Twelve male healthy C57BL/6 wild-type mice weighing 20-25 g and aged 6-8 weeks were divided into a sham operation group ( n=6) and a HIRI group ( n=6); Twelve male healthy C57BL/6 IRF1 gene knockout (IRF1 -/-) mice weighing 20-25 g and aged 6-8 weeks were divided into a sham operation IRF1 -/- group ( n=6) and a HIRI IRF1 -/- group ( n=6). The levels of serum alanine transaminase (ALT) and aspartate transaminase (AST) in mice were measured, and hematoxylin-eosin (HE) staining of liver tissues was performed for Suzuki scoring to evaluate liver injury. Fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to evaluate the mRNA levels of IRF1 and tumor necrosis factor α (TNFα) in liver tissues. Flow cytometry and qRT-PCR were used to detect the proportion and functional changes of M1/M2-type Kupffer cells in liver tissues. IRF1 was overexpressed or knocked down in the mononuclear macrophage cell line ANA1, and a co-culture and hypoxia-reoxygenation system with the hepatocyte cell line AML12 was established. Flow cytometry was used to detect the apoptosis of AML12 cells. Results:At 12 hours after hepatic ischemia-reperfusion in wild-type mice, the liver tissue injury was the most severe. Compared with the sham operation group, the levels of serum ALT [(8 073±83) U/L vs. (81±19) U/L, q=13.59] and AST [(11 170±2 890) U/L vs. (412±210) U/L, q=13.77] in the HIRI group were significantly higher, and the differences were statistically significant (both P<0.001). The Suzuki score reached 5-6 points. At 12 hours after hepatic ischemia-reperfusion in IRF1 gene knockout mice, the liver tissue injury was not obvious. There were no significant differences in the levels of serum ALT [668 (514, 2 344) U/L vs. 254 (147, 285) U/L, q=2.52, P=0.348] and AST [1 936 (1 262, 2 003) U/L vs. 628 (423, 759) U/L, q=1.22, P=0.824] between the HIRI IRF1 -/- group and the sham operation IRF1 -/- group. Compared with the HIRI group, the ratio of M1/M2-type Kupffer cells in the liver of the HIRI IRF1 -/- group decreased [(0.958±0.090) vs. (2.788±0.258), q=2.06, P<0.0001], and the mRNA expression of TNFα decreased [(4.363±0.393) vs. (12.900±5.504), q=5.59, P=0.018], and the differences between the two groups were statistically significant. In the co-culture and hypoxia-reoxygenation experiment using ANA1 cells overexpressing IRF1 and AML12 cells, the proportion of AML12 hepatocytes in late apoptosis was higher than that in the control group [(14.05±4.25) vs. (3.15±1.16), t=2.85, P=0.047], and the difference was statistically significant. In contrast, when the expression of IRF1 was knocked down, the proportion of apoptotic AML12 cells decreased [(9.26±3.04) vs. (13.36±4.64), t=2.15, P=0.098], but the difference was not statistically significant. Conclusion:The IRF1 protein can regulate the polarization of Kupffer cells into M1-type macrophages, promote the inflammatory injury of the liver tissue after ischemia-reperfusion, and increase the apoptosis of hepatocytes.

Liver transplantation techniques have made significant advances in recent years in surgical procedures, expanding liver donor sources and perioperative management, leading to markedly improved patient survival rates. This review focuses on key recent developments in the field of liver transplantation, summarizing practical achievements and technical breakthroughs in areas such as machine perfusion techniques and utilization of marginally viable donors, minimally invasive liver transplantation techniques, and the clinical application of small-and ultra-small-size grafts. Furthermore, it explores the current challenges encountered in clinical practice and analyzes future research priorities and developmental trends.