Adipose progenitor cells(APCs) represent a prominent stromal cellular component of adipose tissue and are now identified as highly heterogenous populations. However, the role of APCs in regulating systemic metabolism remains unknown. Using single cell RNA-sequencing, we investigated the role of the APC subpopulations in regulating development of type 2 diabetes. CD9 + CD55 low APCs are the novel subset identified in this study, which is significantly increased in type 2 diabetic patients. Transplantation of these cells from type 2 diabetic patients into adipose tissue caused glycemic disturbance in mice. Depletion of pathogenic APCs improved obesity-related glycemic disturbance. Collectively, our data provide deeper insights into human APC functionality and highlights APCs as a potential therapeutic target to combat type 2 diabetes. This study has been published in Nature Communications, 2024, 15(1): 4827.

Objective:To explore the mediating effect of postpartum depression in fathers on their parenting competence and breastfeeding support.Methods:From March to October 2022, convenience sampling was used to select 337 fathers of infants aged 4 to 8 weeks in Wuxi Women and Enfants Care Hospital as the research subject. A survey was conducted using the Edinburgh Postnatal Depression Scale (EPDS), Chinese version of Parenting Sense of Competence Scale (C-PSOC), and maternal spouse version Partner Breastfeeding Influence Scale (PBIS). Spearman correlation was used to explore the correlation between postpartum depression in fathers and their parenting competence and breastfeeding support, and the PROCESS plugin was used for mediation effect testing.Results:A total of 337 questionnaires were distributed and 337 were collected, including 314 valid questionnaires with an effective response rate of 93.18% (314/337). Among 314 infant fathers, the EPDS, C-PSOC, and maternal spouse version PBIS scores were 3.00 (2.00, 6.00), 66.00 (62.00, 71.00), and 83.00 (74.00, 90.00), respectively. Father's parenting competence was negatively correlated with father's postpartum depression ( r=-0.435, P<0.01), and positively correlated with father's breastfeeding support ( r=0.480, P<0.01). Father's postpartum depression was negatively correlated with father's breastfeeding support ( r=-0.423, P<0.01). The mediating effect analysis showed that the mediating effect of postpartum depression in fathers between parenting competence and breastfeeding support was 0.341, accounting for 39.51% of the total effect. Conclusions:Postpartum depression in fathers is a mediating variable between their parenting competence and their breastfeeding support. Medical and nursing workers should develop perinatal education programs for fathers, enhance their parenting competence, alleviate their negative emotions, and promote their breastfeeding support.

Objective To investigate the protective effect of adult human liver-derived stem cell exosomes (HLSC-exo) intravenously injected at different time points against acute liver injury induced by concanavalin A (ConA) in mice. Methods HLSC-exo was extracted by differential centrifugation. Western blot was used to measure the expression of the marker proteins CD9 and CD63, and nanoparticle tracking analysis was used to investigate particle size distribution. A total of 56 male C57BL/6 mice were randomly divided into blank control group, ConA model group, and HLSC-exo treatment group. The ConA model group and the HLSC-exo treatment group were further divided into 3-, 6-, and 12-hour subgroups according to the interval between phosphate buffer or HLSC-exo injection and ConA injection. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α), and interleukin-10 (IL-10) were measured, and the gross morphology and histopathology of the liver were compared between groups. 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. Results HLSC-exo was a membranous vesicle with a diameter of 90-110 nm, with a clear saucer-like structure under an electron microscope and marked expression of its specific marker proteins CD9 and CD63. In the blank control group, the levels of ALT and AST were 31.81±6.74 U/L and 69.75±8.30 U/L, respectively. Compared with the blank control group, the 3-, 6-, and 12-hour ConA model groups had significant increases in the levels of ALT and AST (all P < 0.001); compared with the 3-and 6-hour ConA model groups, the 3-and 6-hour HLSC-exo treatment groups had significant reductions in the levels of ALT and AST (225.58±115.59 U/L vs 1989.32±347.67 U/L, 1174.71±203.30 U/L vs 2208.33±349.96 U/L, 303.53±126.68 U/L vs 2534.27±644.72 U/L, 1340.70±262.56 U/L vs 2437.13±288.13 U/L, all P < 0.001); compared with the 6-hour HLSC-exo treatment group, the 3-hour HLSC-exo treatment group had significantly greater reductions ( P < 0.001). In the blank group, the levels of IL-10 and TNF-α were 313.51±10.97 pg/ml and 476.05±7.31 pg/ml, respectively. Compared with the blank control group, the 3-, 6-, and 12-hour ConA model groups had a significant reduction in the level of IL-10 (all P < 0.001); compared with the 3-and 6-hour ConA model groups, the 3-and 6-hour HLSC-exo treatment groups had a significant increase in the level of IL-10(331.61±10.46 pg/ml vs 266.20±8.15 pg/ml, 288.13±10.74 pg/ml vs 264.41±9.12 pg/ml, both P < 0.001); compared with the 6-hour HLSC-exo treatment group, the 3-hour HLSC-exo treatment group had a significantly greater increase ( P < 0.001). Compared with the blank control group, the 3-, 6-, and 12-hour ConA model groups had a significant increase in the level of TNF-α (all P < 0.001); compared with the 3-and 6-hour ConA model groups, the 3-and 6-hour HLSC-exo treatment groups had a significant reduction in the level of TNF-α (478.26±12.99 pg/ml vs 551.31±17.70 pg/ml, 515.58±7.18 pg/ml vs 556.21±11.15 pg/ml, both P < 0.001); compared with the 6-hour HLSC-exo treatment group, the 3-hour HLSC-exo treatment group had a significantly greater reduction ( P < 0.001). Compared with the 3-and 6-hour ConA model groups in terms of the gross morphology and histopathology of the liver, the 3-and 6-hour HLSC-exo treatment groups had a significant reduction in the degree of hepatocyte necrosis, and the 3-hour HLSC-exo treatment group had a basically complete lobular structure, with sporadic spotty necrosis; the 12-hour HLSC-exo treatment group had no significant improvement in hepatocyte necrosis compared with the 12-hour ConA model group. Conclusion Intravenous injection of adult HLSC-exo can alleviate acute liver injury induced by ConA in mice, and injection at 3 hours in advance has the most significant protective effect. Regulation of cytokines is one of the important mechanisms for HLSC-exo to alleviate liver injury.

A new definition of metabolic dysfunction-associated fatty liver disease (MAFLD) has recently been proposed. We aim to examine the associations of MAFLD, particularly its discordance from non-alcoholic fatty liver disease (NAFLD), with the progression of elevated brachial-ankle pulse wave velocity (baPWV) and albuminuria in a community-based study sample in Shanghai, China. After 4.3 years of follow-up, 778 participants developed elevated baPWV and 499 developed albuminuria. In comparison with the non-MAFLD group, the multivariable adjusted odds ratio (OR) of MAFLD group for new-onset elevated baPWV was 1.25 (95% confidence interval (CI) 1.01-1.55) and 1.35 (95% CI 1.07-1.70) for albuminuria. Participants without NAFLD but diagnosed according to MAFLD definition were associated with higher risk of incident albuminuria (OR 1.77; 95% CI 1.07-2.94). Patients with MAFLD with high value of hepamet fibrosis score or poor-controlled diabetes had higher risk of elevated baPWV or albuminuria. In conclusion, MAFLD was associated with new-onset elevated baPWV and albuminuria independently of body mass index, waist circumference, and hip circumference. Individuals without NAFLD but diagnosed as MAFLD had high risk of albuminuria, supporting that MAFLD criteria would be practical for the evaluation of long-term risk of subclinical atherosclerosis among fatty liver patients.
Humans ; Pulse Wave Analysis ; Albuminuria ; Ankle Brachial Index ; Non-alcoholic Fatty Liver Disease/diagnosis* ; Vascular Stiffness ; Prospective Studies ; Risk Factors ; China/epidemiology*

Objective:To evaluate the relationship between preoperative mild cognitive impairment (MCI) and postoperative delirium (POD) in the patients undergoing total knee/hip arthroplasty.Methods:A total of 625 patients, aged 50-90 yr, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, undergoing total knee and hip arthroplasty under combined spinal-epidural anesthesia from September 2021 to February 2022, were included.One day before surgery, the cognitive function was assessed using the Mini-Mental State Examination and the Montreal Cognitive Assessment scale.The patients were divided into non-MCI group (NMCI group) and MCI group according to the diagnostic criteria of MCI.The concentrations of amyloid beta 40 (Aβ40), amyloid beta 42 (Aβ42), total tau protein (T-tau) and phosphorylated tau protein (P-tau) in cerebrospinal fluid (CSF) were detected by enzyme-linked immunosorbent assay.The development of POD was assessed on 1-7 days after operation.The relationship between MCI and POD and relationship of concentrations of β40, Aβ42, T-tau and P-tau in CSFA, Aβ40/T-tau ratio, Aβ42/P-tau ratio and Aβ42/T-tau ratio with POD and MCI were analyzed using binary logistic regression.Results:Compared with NMCI group, the incidence of POD was significantly increased, the concentrations of Aβ42 and Aβ40 in CSF, Aβ40/T-tau ratio, Aβ42/P-tau ratio and Aβ42/T-tau ratio were decreased, and T-tau and P-tau concentrations in CSF were increased in MCI group ( P<0.05).The results of logistic regression analysis showed that before and after adjusting for confounding factors, increased MCI and concentrations of P-tau and T-tau in CSF were the risk factors for POD, and increased concentrations of Aβ42 and Aβ40 in CSF, Aβ40/T-tau ratio, Aβ42/P-tau ratio and Aβ42/T-tau ratio were protective factors for POD ( P<0.05); elevated concentrations of P-tau and T-tau in CSF were risk factors for MCI before and after adjusting for confounding factors, and increased concentrations of Aβ4 in CSF, Aβ40/T-tau ratio, Aβ42/P-tau ratio, and Aβ42/T-tau ratio were protective factors for MCI after adjusting for confounding factors ( P<0.05). Conclusions:Preoperative MCI are risk factors for POD in the patients undergoing total knee/hip arthroplasty.

Objective To establish a new patient-derived xenograft (PDX) model of human liver cancer by inoculating the complex of human primary liver cancer cells and a novel microcarrier (microcarrier 6) into mice with normal immune function. Methods Primary liver cancer cells were isolated and extracted from the fresh human liver cancer tissue of five patients and were then co-cultured with microcarrier 6 to construct a three-dimensional tumor cell culture model in vitro . According to the type of graft, 75 male C57BL/6 mice were divided into cell control group, microcarrier control group, and experimental group (each sample corresponded to three groups, with 15 groups in total and 5 mice in each group). The liver cancer cell-microcarrier complex was implanted into the mice by subcutaneous inoculation, and tumor formation time, tumor formation rate, and histopathological manifestations were observed. The Fisher's exact test was used for comparison of categorical data between two groups. Results As for the liver cancer cells from the five patients, tumor formation was observed in the mice corresponding to three patients. In these three experiments, tumor formation was not observed in the control groups and was only observed in the experimental groups, and 12 of the 15 mice in the experimental groups had successful tumor formation, with a tumor formation rate as high as 80%, which was significantly different from that in the cell control groups and the microcarrier control groups (all P < 0.05). The tumor formation time was 5-7 days; the xenograft tumor grew rapidly, and HE staining showed nested or flaky cells with obvious heteromorphism, with the presence of pathological mitosis; immunohistochemical staining showed positive CK8/18, Hep, and Gpc-3, which was in accordance with the characteristics of human liver cancer cells. Conclusion This experiment successfully establishes a new PDX model of human liver cancer based on the complex of microcarrier 6 and human primary liver cancer cells in mice with normal immunity. This model can be used to better elucidate the mechanism of the development and progression of liver cancer in the body with normal immunity, and besides, it also provides a new animal model with higher value for the precise treatment of liver cancer.

Objective:To investigate the inhibitory effects of nucleolar and spindle associated protein 1 (NUSAP1) on lung cancer and the related mechanisms.Methods:A549 cells were transfected with NUSAP1 siRNA, the cell proliferation, migration and invasion, and apoptosis were detected by CCK8, Transwell and flow cytometry, respectively. Western blot was used to detect the expressions of apoptosis and AKT/mTOR signal pathway related proteins.Results:Compared with the negative control group, the proliferation [(0.610±0.058) vs (1.724±0.067), P<0.05], migration [(178.267±14.780) vs (272.464±36.232), P<0.05] and invasion [(73.527±6.617) vs (120.585±13.235), P<0.05] of NUSAP1 deleted A549 cells were significantly inhibited, while the apoptosis [(3.572±0.214)% vs (11.358±1.047)%, P<0.05] was significantly increased. The expressions of apoptosis related protein Bax and active-caspase 3 were increased ( P<0.05), while the expressions of anti-apoptosis protein Bcl-2 and proliferation related protein P70, the phosphorylation levels of AKT and mTOR were reduced in NUSAP1 knockdown cells ( P<0.05). Conclusion:NUSAP1 knockdown can inhibit the proliferation, migration and invasion, and promote the apoptosis of tumor cells through suppressing AKT/mTOR signaling pathway in lung cancer cells.

Objective:To investigate the inhibitory effects of nucleolar and spindle associated protein 1 (NUSAP1) on lung cancer and the related mechanisms.Methods:A549 cells were transfected with NUSAP1 siRNA, the cell proliferation, migration and invasion, and apoptosis were detected by CCK8, Transwell and flow cytometry, respectively. Western blot was used to detect the expressions of apoptosis and AKT/mTOR signal pathway related proteins.Results:Compared with the negative control group, the proliferation [(0.610±0.058) vs (1.724±0.067), P<0.05], migration [(178.267±14.780) vs (272.464±36.232), P<0.05] and invasion [(73.527±6.617) vs (120.585±13.235), P<0.05] of NUSAP1 deleted A549 cells were significantly inhibited, while the apoptosis [(3.572±0.214)% vs (11.358±1.047)%, P<0.05] was significantly increased. The expressions of apoptosis related protein Bax and active-caspase 3 were increased ( P<0.05), while the expressions of anti-apoptosis protein Bcl-2 and proliferation related protein P70, the phosphorylation levels of AKT and mTOR were reduced in NUSAP1 knockdown cells ( P<0.05). Conclusion:NUSAP1 knockdown can inhibit the proliferation, migration and invasion, and promote the apoptosis of tumor cells through suppressing AKT/mTOR signaling pathway in lung cancer cells.

OBJECTIVE: To carry out phenotypic and genotypic analysis for two Chinese pedigrees affected with coagulation factor XII (F XII) deficiency. METHODS: Plasma prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), thrombin time (TT), and blood coagulation factor VIII, IX, XI, XII activity (FVIII:C, FIX:C, FXI:C, FXII:C) were determined with one stage clotting assay on a STAGO coagulation analyzer. FXII antigen was determined with an enzyme linked immunosorbent assay (ELISA). The 14 exons and their flanking sequences of the F12 gene were subjected to PCR amplification and Sanger sequencing. The conservation and structure of mutant protein were analyzed with MegAlign software and PYMOL software. RESULTS: The APTT of the probands was significantly prolonged, while their FXII:C and FXII:Ag were significantly reduced. Genetic analysis of the proband has revealed three novel mutations in the F12 gene, including g.5972G>A splice site mutation in intron 5, g.8810_8814delGTCTA in exon 14, and g.6259G>A (p.Pro182Leu) in exon 7. In addition, a previously known mutation IVS13-1G>A has been found. CONCLUSION Four mutations have been identified in the two Chinese pedigrees, among which three were novel. Above mutations probably played a role in the defect of FXII in the two pedigrees.
Exons ; Factor XII ; genetics ; Factor XII Deficiency ; genetics ; Genetic Testing ; Humans ; Pedigree

With the development of science and technology,medical simulation has been applied extensively.The application of simulation technique in teaching hospitals has become a new choice in modern medical education.As the most basic and important clinical ability,airway management has become a popular training program in China's teaching hospitals.This paper summarizes the current situation of the simulation training of airway management in teaching hospitals at home and abroad,concludesthe existing problems in the simulation teaching of airway management of teaching hospitals in China,such as narrow range of training objects,lack of professional teaching staff,unscientific curriculum design and outdated training model,etc.Then puts forward the countermeasures of expanding the training coverage,establishing the professional teaching team,designing the curriculum design of science,and introducing advanced simulation equipment to improve the quality of simulated teaching.