Objective:To evaluate the left ventricular（LV）function in heart transplant（HTx）patients with post-transplant diabetes（PTDM），and to examine the relevance of PTDM and LV function to the patient's prognosis.Methods:Two hundred and thirteen adult HTx patients who underwent echocardiography at Union Hospital，Tongji Medical College，Huazhong University of Science and Technology between January 2018 and January 2022 were prospectively included. The patients were divided into PTDM group（ n=86）and Non-PTDM group（ n=127）. LV function parameters were acquired using conventional and two-dimensional speckle-tracking echocardiography（2D-STE），and were compared between the two groups. The primary endpoints included all-cause mortality or transplant-related readmission. Results:Compared with Non-PTDM group，the LV mass of PTDM group was higher，the LV ejection fraction，LV global longitudinal strain（GLS），peak systolic global longitudinal strain rate，and early diastolic global longitudinal strain rate（dGLSr）were lower（all P＜0.05）. After a median follow-up period of 37.6（29.3）months，27 patients experienced clinical events. A multivariate analysis revealed that PTDM（ HR=2.198，95% CI=1.018-4.743， P=0.045）and low GLS（ HR=6.456，95% CI=2.889-14.426， P＜0.001）were independent predictors of adverse clinical events after adjustment for dGLSr，body mass index and age. After subdividing the two groups into 4 subgroups by the cutoff value of GLS（16.5%），the prognosis was worst for HTx patients with PTDM and low GLS. Conclusions:HTx patients with PTDM have worse LV systolic and diastolic function than those without PTDM. Management of HTx patients with PTDM may be improved using GLS guidance.

Objective:To evaluate the left ventricular（LV）function in heart transplant（HTx）patients with post-transplant diabetes（PTDM），and to examine the relevance of PTDM and LV function to the patient's prognosis.Methods:Two hundred and thirteen adult HTx patients who underwent echocardiography at Union Hospital，Tongji Medical College，Huazhong University of Science and Technology between January 2018 and January 2022 were prospectively included. The patients were divided into PTDM group（ n=86）and Non-PTDM group（ n=127）. LV function parameters were acquired using conventional and two-dimensional speckle-tracking echocardiography（2D-STE），and were compared between the two groups. The primary endpoints included all-cause mortality or transplant-related readmission. Results:Compared with Non-PTDM group，the LV mass of PTDM group was higher，the LV ejection fraction，LV global longitudinal strain（GLS），peak systolic global longitudinal strain rate，and early diastolic global longitudinal strain rate（dGLSr）were lower（all P＜0.05）. After a median follow-up period of 37.6（29.3）months，27 patients experienced clinical events. A multivariate analysis revealed that PTDM（ HR=2.198，95% CI=1.018-4.743， P=0.045）and low GLS（ HR=6.456，95% CI=2.889-14.426， P＜0.001）were independent predictors of adverse clinical events after adjustment for dGLSr，body mass index and age. After subdividing the two groups into 4 subgroups by the cutoff value of GLS（16.5%），the prognosis was worst for HTx patients with PTDM and low GLS. Conclusions:HTx patients with PTDM have worse LV systolic and diastolic function than those without PTDM. Management of HTx patients with PTDM may be improved using GLS guidance.

Objective To explore the expression and clinical value of serum calprotectin and toll like receptor 2(TLR2)with type 2 diabetic kidney disease(DKD).Method According to the levels of UACR,90 T2DM patients treated in our hospital from January 2019 to January 2022 were divided into normal albuminuria group(Con,UACR<30 mg/g),microalbuminuria group(Micro,UACR 30～300 mg/g),and macroalbuminuria group(Macro,UACR>300 mg/g),30 cases per group.Result The levels of BMI,HbAlc,calprotectin,TLR2,and NLRP3 increased sequentially from Con,Micro to Macro groups(P<0.05),while eGFR in the Macro group was lower than that in the Con or Micro groups(P<0.05).Pearson correlation analysis showed that serum calprotectin was positively correlated with BMI,WC,SBP,FPG,HbAlc,TC,TG,Scr,UACR(P<0.05 or P<0.01),and negatively correlated with eGFR(P<0.01);NLRP3 is positively correlated with BMI,WC,SBP,FPG,HbAlc,TC,TG,Scr,SUA,and UACR(P<0.01),and negatively correlated with eGFR(P<0.01);TLR2 was positively correlated with BMI,WC,SBP,FPG,HbAlc,TC,TG,Scr and UACR(P<0.05 or P<0.01),and negatively correlated with eGFR(P<0.01).Multiple linear regression analysis showed that FPG,HbAlc,TC,Scr,calprotectin,and TLR2 were the influencing factors of UACR.Receiver operating characteristic(ROC)curve analysis showed that the area under the curve for diagnosing DKD with serum calprotectin and TLR2 was 0.883 and 0.961,with sensitivities of 73.33%and 96.67%,and specificity of 100.00%and 83.33%.Conclusion Serum calprotectin and TLR2 are closely related to the occurrence and development of DKD.The diagnostic value of TLR2 for DKD is superior to serum calprotectin.

Objective:To investigate the central mechanism of moxibustion in treating chronic inflammatory visceral pain(CIVP)and its analgesic effect from the perspective of the p38 mitogen-activated protein kinase(MAPK)/Ets-like transcription factor 1(ELK1)signaling pathway in the spinal cord. Methods:Clean-grade male Sprague-Dawley rats were randomly divided into a normal group,a model group,a herb-partitioned moxibustion(HPM)group,a sham-HPM group,a p38 MAPK inhibitor group,and a dimethyl sulfoxide(DMSO)group.CIVP rat models were prepared using an enema mixture of 2,4,6-trinitrobenzene sulfonic acid solution and 50%ethanol.The HPM group was treated with HPM;the sham-HPM group was treated the same as the HPM group,but the moxa cones were not ignited;rats in the p38 MAPK inhibitor group received L5-L6 intrathecal injection of p38 MAPK inhibitor(SB203580);rats in the DMSO group received L5-L6 intrathecal injection of 2%DMSO.Abdominal withdrawal reflex(AWR),mechanical withdrawal threshold(MWT),and thermal withdrawal latency(TWL)were used to observe pain-related behaviors in each group.Hematoxylin-eosin staining was used to observe the morphological changes in rat colon tissue.Western blotting and real-time quantitative reverse-transcription polymerase chain reaction were used to detect the phosphorylated protein and mRNA expression of apoptosis signal-regulating kinase 1(ASK1),MAPK kinase(MKK)3/6,p38 MAPK,ELK1,and mitogen and stress-activated protein kinase 1(MSK1)in the spinal cord. Results:Compared with the normal group,CIVP rats had severe colonic inflammatory injuries,and the pathological injury scores increased significantly,along with increased AWR scores under different colorectal distension(CRD)stimulation pressures and decreased MWT and TWL;the mRNA and phosphorylated protein expression of p38 MAPK,ELK1,MSK1,ASK1,MKK3,and MKK6 all increased in the spinal cord(P<0.01).After HPM treatment,the colon injuries were repaired,and the pathological injury scores decreased;under different CRD stimulation pressures,the AWR scores decreased,and the MWT and TWL increased;the mRNA and phosphorylated protein expression of p38 MAPK,ELK1,ASK1,and MKK3 in the spinal cord also decreased,with statistically significant differences compared with the model group and the sham-HPM group(P<0.01).There were no significant differences in the above indicators between the HPM group and the p38 MAPK inhibitor group(P>0.05),and the same was true regarding the comparisons between the model group and the DMSO group. Conclusion:HPM exerted analgesic effects via downregulating the mRNA and phosphorylated protein expression of ASK1,MKK3,p38 MAPK,and ELK1 in the spinal cord of CIVP rats.The inhibition of spinal p38 MAPK/ELK1 signaling pathway activation may be one of the mechanisms by which HPM relieves pain in CIVP.

Female ; Humans ; Hypoglycemic Agents/therapeutic use* ; Insulin Resistance ; Metformin/therapeutic use* ; Phosphatidate Phosphatase ; Pioglitazone/therapeutic use* ; Polycystic Ovary Syndrome/genetics*

The Ly-6 and uPAR (LU) domain-containing proteins represent a large family of cell-surface markers. In particular, mouse Ly-6A/Sca-1 is a widely used marker for various stem cells; however, its human ortholog is missing. In this study, based on a systematic survey and comparative genomic study of mouse and human LU domain-containing proteins, we identified a previously unannotated human gene encoding the candidate ortholog of mouse Ly-6A/Sca-1. This gene, hereby named LY6A, reversely overlaps with a lncRNA gene in the majority of exonic sequences. We found that LY6A is aberrantly expressed in pituitary tumors, but not in normal pituitary tissues, and may contribute to tumorigenesis. Similar to mouse Ly-6A/Sca-1, human LY6A is also upregulated by interferon, suggesting a conserved transcriptional regulatory mechanism between humans and mice. We cloned the full-length LY6A cDNA, whose encoded protein sequence, domain architecture, and exon-intron structures are all well conserved with mouse Ly-6A/Sca-1. Ectopic expression of the LY6A protein in cells demonstrates that it acts the same as mouse Ly-6A/Sca-1 in their processing and glycosylphosphatidylinositol anchoring to the cell membrane. Collectively, these studies unveil a novel human gene encoding a candidate biomarker and provide an interesting model gene for studying gene regulatory and evolutionary mechanisms.
Humans ; Membrane Proteins/genetics* ; Pituitary Neoplasms/genetics* ; Biomarkers

Objective:To observe the distribution characteristics of fungi, bacteria and Demodex in the eyelid margin of patients with blepharitis and without blepharitis at different ages. Methods:A cross-sectional study was conducted.A total of 98 patients diagnosed with anterior blepharitis and 99 patients diagnosed with posterior blepharitis in Henan Eye Hospital from March 2021 to June 2022 were enrolled as anterior blepharitis group and posterior blepharitis, respectively.Additionally, 100 patients with an initial diagnosis of refractive error and 200 patients with vitreous opacity were enrolled during the same period as a non-blepharitis group.All patients underwent examinations for lid margin fungi, bacteria and eyelash Demodex, as well as fungal spores and ciliary Demodex count.The differences in the positive rate and load of palpebral fungi, bacteria and eyelash Demodex were compared between anterior and posterior blepharitis groups, as well as across different ages in non-blepharitis group.This study protocol was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECKY-2019[18]).All patients were informed about the purpose and methods of the study.Written informed consent was obtained from each patient. Results:There were significant differences in the positive rates of bacteria, fungi and Demodex and the load of Demodex in the non-blepharitis group at different ages ( χ2=28.34, 10.36, 51.57, H=35.66; all at P<0.01).The positive rates of palpebral bacteria and ciliary Demodex and the load of Demodex were significantly higher and the palpebral fungi positive rate was significantly lower in the ≥60 years old than in the <60 years old (all at P<0.05).There were significant differences in the positive rates of bacteria and fungi among anterior blepharitis, posterior blepharitis and non-blepharitis groups ( χ2=18.99, 6.36; all at P<0.01).The palpebral bacteria positive rate was significantly higher in anterior blepharitis group than in posterior blepharitis and non-blepharitis groups, and the palpebral fungi positive rate was significantly higher in anterior blepharitis and posterior blepharitis groups than in non-blepharitis group (all at P<0.05).There was no significant difference in the ciliary Demodex detection rate among the three groups ( χ2=0.16, P=0.74).The number of palpebral fungi spores and eyelash Demodex counts were higher in anterior and posterior blepharitis groups than in non-blepharitis group, and the differences were statistically significant (all at P<0.05).The positive rate of palpebral margin bacteria in ciliary Demodex-positive group was 45.7%(156/341), which was significantly higher than 25.6%(40/156) in ciliary Demodex-negative group ( χ2=17.20, P<0.01), and there was no significant difference in the positive rate of palpebral margin fungi between them ( χ2=0.11, P=0.70). Conclusions:In the population with normal eyelid margin, the infection of Demodex and bacteria in lid margin increases and fungal infection decreases in the ≥60 years old.Fungal and bacterial infections are the main sources of palpebral infection in patients with blepharitis, and positive detection of Demodex increases the chance of bacterial infection.

Objective:To investigate the expression of adenosine 5'-monophosphate-activated protein kinase (AMPK) phosphorylation in corneal epithelial cells and the effects of fungus on AMPK phosphorylation and interleukin-6 (IL-6) production in corneal epithelial cells.Methods:The human immortalized corneal epithelial cell line was selected.The safe concentration range of AMPK agonist 5-aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR) (100, 300, 500, 1 000 μmol/L) and inhibitor Compound C (10.0, 12.5, 15.0, 17.5, 20.0 μmol/L) on corneal epithelial cells was screened by multi-function real-time unlabeled cell analyzer.Corneal epithelial cells without any treatment were used as the normal control group, and those co-cultured with spores were used as the spore control group.Corneal epithelial cells co-cultured with spores were treated with AICAR and Compound C for 4 hours in the AICAR group and Compound C group, respectively.The expression of phosphorylated AMPK (p-AMPK) and AMPK in corneal epithelial cells was detected by Western blot, and the concentration of IL-6 in the culture supernatant was determined by enzyme-linked immunosorbent assay (ELISA).Results:After treatment with different concentrations of AICAR for different periods, there was no statistical significance in the cell index of corneal epithelial cells (all at P>0.05). The cell index of corneal epithelial cells was increased with 10.0 μmol/L and 12.5 μmol/L Compound C treatment compared with that of the normal control group.The expression levels of p-AMPK were 0.67±0.15, 2.57±0.12, 3.67±0.58 and 1.50±0.50, respectively, in the normal control group, spore control group, AICAR group and Compound C group, showing a statistically significant difference among them ( F=32.820, P<0.001). The expression level of p-AMPK was significantly higher in the spore control group compared with the normal control group ( P<0.001). The expression level of p-AMPK in the AICAR group was higher than that in the spore control group, and the expression level of p-AMPK in the Compound C group was lower than that in the spore control group, and the differences were statistically significant (both at P=0.010). There was no significant difference in the relative expression level of AMPK among the four groups ( F=0.120, P=0.950). The expression levels of IL-6 concentration in the normal control group, spore control group, AICAR group and Compound C group were (107.81±17.15), (156.32±9.94), (167.96±14.16) and (127.42±19.75)pg/ml, respectively, showing a statistically significant difference among them ( F=15.210, P<0.001). The IL-6 concentration of the spore control group was higher than that of the normal control group, and the difference was statistically significant ( P<0.001). The IL-6 concentration of the AICAR group was higher than that of the spore control group, but the difference was not statistically significant ( P=0.260). The IL-6 concentration of the Compound C group was lower than that of the spore control group, and the difference was statistically significant ( P=0.010). Conclusions:In corneal epithelial cells, AMPK phosphorylation is found, which is enhanced after fungal spores stimulation, and the secretion of IL-6 increases.

Objective:To summarize the ultrasonophic features of left atrial appendage aneurysm, and to provide an important reference for the early and accurate diagnosis of left atrial appendage aneurysm.Methods:Patients with atrial appendage aneurysm have no obvious symptoms in the early stage, and there are many difficulties and challenges in diagnosis. This paper analyzed and summarized the diagnostic characteristics of a child with left atrial appendage aneurysm by combining the prenatal and postnatal ultrasonic imaging characteristics.Results:Echocardiography is the first choice for the diagnosis of left atrial appendage aneurysm. Some cases can make precise diagnosis prenatally.Conclusions:Echocardiography is the preferred imaging examination method for evaluating left atrial appendage aneurysm. Multimodal imaging technology can identify and diagnose left atrial appendage aneurysm early and accurately, and provide important basis for clinical diagnosis and treatment plan.

【Objective】 To explore the role and value of applied muscle tension (AMT) in preventing vasovagal nerve reaction (VVR) in blood donors. 【Methods】 A total of 2 992 people, susceptible to suffer VVR from May 2020 to may 2022, were randomly divided into control group (1406 cases) and observation group (1 586 cases). The control group was not given AMT intervention, while the observation group received AMT intervention at different periods during blood donation. The changes of systolic blood pressure, diastolic blood pressure, heart rate and psychological state of anxiety (self-rating anxiety scale, SAS) of blood donors were monitored in the two groups at each period to compare the occurrence of VVR. 【Results】 There were no statistically significant differences in blood pressure and heart rate between the two groups before blood donation (P>0.05). The parameters were relatively stable in observation group during and after donation, but significantly different from that of the controls(P>0.05). SAS score was similar in two groups before blood donation(P>0.05), while decreased in observation group during and after donation in comparison with the controls(P<0.05). The incidence of VVR in the observation group was 3.09%, which was significantly lower than that in the control group (7.97%)(P<0.05). The incidence of VVR was 2.18% after AMT exercise during blood donation. 【Conclusion】 AMT intervention in different periods of blood donation can significantly reduce the occurrence of VVR.