Early-onset neonatal sepsis (EONS) is a systemic inflammatory response syndrome caused by bacterial and fungal infections within 3 days after birth, which is one of the important causes of poor prognosis and even death in neonates.Early accurate diagnosis and timely treatment are crucial to improving the prognosis and reducing the mortality and unreasonable use of antibiotics.Because umbilical cord blood shares the same cell composition with fetal peripheral blood at the end of pregnancy, and has the advantages of easy availability and painlessness, many researchers have been devoted to exploring umbilical cord blood markers related to the diagnosis of EONS in recent years.Most studies suggest that umbilical cord blood culture, procalcitonin, C-reactive protein and interleukin-6 should be routinely used as single indicators for clinical diagnosis of EONS.The combination of two or more biomarkers may be more accurate for the diagnosis of EONS, which, however, needs to be confirmed with more trials, and it is also a significant direction of future research.In this article, progress in relevant research was reviewed in order to provide reference for early diagnosis of EONS.

ObjectiveTo explore the mechanism by which Xiaoyaosan regulates HPT axis dysfunction in the rat model with the syndrome of liver depression and spleen deficiency by observing its effect on the glycoprotein hormone α-subunit （CGA）/glutathione peroxidase 2 （GPX2）/thyroid-stimulating hormone β-subunit （TSHβ） pathway for thyroid hormone synthesis. MethodsSeventy-two male SD rats were randomized into six groups： normal， model， high-dose （16.7 g·kg^-1）， medium-dose （8.35 g·kg^-1）， and low-dose （4.175 g·kg^-1） Xiaoyaosan， and fluoxetine （0.001 8 g·kg^-1） groups， with 12 rats in each group. The rat model of liver depression and spleen deficiency was induced by chronic restraint stress for 21 days. The intervention groups were treated with Xiaoyaosan decoctions or fluoxetine suspension， respectively. After modeling， hematoxylin-eosin staining was employed to observe morphological changes in the thyroid and pituitary tissue of the rats. Serum levels of triiodothyronine （T3）， tetraiodothyronine （T4）， and thyroid-stimulating hormone （TSH） were measured by enzyme-linked immunosorbent assay （ELISA）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were employed to determine the mRNA and protein levels， respectively， of TSH receptor （TSHR） in the thyroid tissue， thyrotropin-releasing hormone receptor （TRHR） and TSHβ in the pituitary tissue， and thyrotropin-releasing hormone （TRH）， CGA， GPX2， and TSHβ in the hypothalamic tissue. ResultsCompared with the normal group， the model group showed significant atrophy and irregularity of thyroid follicles， a marked reduction in colloid secretion， extensive vacuolar degeneration of adenocytes in the anterior pituitary， lowered serum levels of T3， T4， and TSH （P<0.01）， and down-regulated mRNA and protein levels of TSHR in the thyroid tissue， TRHR and TSHβ in the pituitary tissue， and TRH， CGA， GPX2， and TSHβ in the hypothalamic tissue （P<0.01）. Compared with the model group， high- and medium-dose Xiaoyaosan and fluoxetine alleviated the pathological changes in the thyroid and pituitary tissue， outperforming the low-dose Xiaoyaosan group. Moreover， they elevated the serum levels of T3， T4， and TSH （P<0.05， P<0.01）. The serum TSH level was also elevated in the low-dose Xiaoyaosan group （P<0.05）. The mRNA and protein levels of TSHR in the thyroid， TRHR and TSHβ in the pituitary， and TRH， CGA， GPX2， and TSHβ in the hypothalamus were up-regulated in the high- and medium-dose Xiaoyaosan groups （P<0.05， P<0.01）. Additionally， the mRNA and protein levels of TSHβ in the hypothalamus were up-regulated in the low-dose Xiaoyaosan group （P<0.01）. In the fluoxetine group， the mRNA and protein levels of TSHR in the thyroid， TRHR in the pituitary， and TRH， CGA， and GPX2 in the hypothalamus were up-regulated （P<0.05， P<0.01）. ConclusionThe downregulation of CGA/GPX2/TSHβ pathway may be one of the biological mechanisms underlying HPT axis dysfunction in the rat model with the syndrome of liver depression and spleen deficiency. Xiaoyaosan may regulate the HPT axis dysfunction by up-regulating the CGA/GPX2/TSHβ pathway.

Objective:To investigate the trajectory of frailty in elderly patients on maintenance hemodialysis(MHD)following SARS-CoV-2 infection and its associated risk factors.Methods:This prospective cohort study focused on elderly patients who underwent baseline frailty assessment(T0)during hemodialysis treatment at Beijing Friendship Hospital for over 3 months between December 1st, 2022, and December 31th, 2022, and were diagnosed with SARS-CoV-2 infection.The Fried Frailty Phenotype was evaluated at 1 month(T1), 3 months(T2), and 6 months(T3)post-infection.Frailty trajectory after infection was analyzed using repeated measurement ANOVA.Patients were divided into stable/improvement or exacerbation groups based on their frailty status at T0 and T3, with logistic regression analysis employed to identify risk factors for different frailty trajectories.Results:A total of 130 elderly maintenance hemodialysis patients, with a median age of 66 years(range: 63-71 years)and 62 males(47.7%), were included in the study.Six months after the infection, a majority of surviving patients saw their frailty scores return to baseline levels.Specifically, 72 patients(55.4%)either maintained or improved to robust or pre-frail states, while 9 patients(6.9%)progressed to a pre-frail state, 18 patients(13.8%)progressed to a frail state, and 31 patients(23.8%)remained in a frail state.Results from multivariate logistic regression analysis indicated that low grip strength( OR: 6.30, 95% CI: 1.48-26.73)and all-cause hospitalization( OR: 5.01, 95% CI: 1.19-21.03)were identified as risk factors for non-frail patients transitioning to frailty( P<0.05). Conclusions:The majority of elderly maintenance hemodialysis patients who survived SARS-CoV-2 infection returned to their baseline level of frailty or showed improvement within 6 months.Non-frail patients with low grip strength or those who were hospitalized were more likely to deteriorate towards frailty.

Objective To explore the impact of change in oxygen concentration on the expression of angiopoietin-like protein 8(ANGPTL8)by endothelial cells(HPAECs)of human pulmonary artery,and the role and mecha-nism of ANGPTL8 in pulmonary hypertension(PH).Methods HPAECs were treated under hypoxic and hyperoxic conditions,and the expression level of ANGPTL8 was detected using Western blot and PCR.The changes in endo-thelial-mesenchymal transition(EndMT)and ERK signaling pathway activity were analyzed.Simultaneously,new-born rats were exposed to hyperoxia to develop a bronchopulmonary dysplasia(BPD)model.The expression of ANGPTL8 protein and changes in the ERK signaling pathway in lung tissue were observed.Results Under hypoxic condition,the protein expression of ANGPTL8 in HPAECs was significantly increased accompanied by inhibition of the ERK signaling pathway.ANGPTL8 promoted the EndMT process induced by hypoxia(P<0.05)and silencing the expression of ANGPTL8 resulted in a partial reversal of EndMT.The protein expression of ANGPTL8 was decreased in hyperoxia-exposed HPAECs and rat lung tissues accompanied by the activation of the ERK signaling pathway(P<0.05).Conclusions ANGPTL8 is highly sensitive to the change of oxygen concentration in HPAECs and closely correlated to its expression level and to the activity of ERK signaling pathway.This result suggests that ANGPTL8 may have potential regulatory effects on the development of PH.

Objective:To investigate the trajectory of frailty in elderly patients on maintenance hemodialysis(MHD)following SARS-CoV-2 infection and its associated risk factors.Methods:This prospective cohort study focused on elderly patients who underwent baseline frailty assessment(T0)during hemodialysis treatment at Beijing Friendship Hospital for over 3 months between December 1st, 2022, and December 31th, 2022, and were diagnosed with SARS-CoV-2 infection.The Fried Frailty Phenotype was evaluated at 1 month(T1), 3 months(T2), and 6 months(T3)post-infection.Frailty trajectory after infection was analyzed using repeated measurement ANOVA.Patients were divided into stable/improvement or exacerbation groups based on their frailty status at T0 and T3, with logistic regression analysis employed to identify risk factors for different frailty trajectories.Results:A total of 130 elderly maintenance hemodialysis patients, with a median age of 66 years(range: 63-71 years)and 62 males(47.7%), were included in the study.Six months after the infection, a majority of surviving patients saw their frailty scores return to baseline levels.Specifically, 72 patients(55.4%)either maintained or improved to robust or pre-frail states, while 9 patients(6.9%)progressed to a pre-frail state, 18 patients(13.8%)progressed to a frail state, and 31 patients(23.8%)remained in a frail state.Results from multivariate logistic regression analysis indicated that low grip strength( OR: 6.30, 95% CI: 1.48-26.73)and all-cause hospitalization( OR: 5.01, 95% CI: 1.19-21.03)were identified as risk factors for non-frail patients transitioning to frailty( P<0.05). Conclusions:The majority of elderly maintenance hemodialysis patients who survived SARS-CoV-2 infection returned to their baseline level of frailty or showed improvement within 6 months.Non-frail patients with low grip strength or those who were hospitalized were more likely to deteriorate towards frailty.

Early-onset neonatal sepsis (EONS) is a systemic inflammatory response syndrome caused by bacterial and fungal infections within 3 days after birth, which is one of the important causes of poor prognosis and even death in neonates.Early accurate diagnosis and timely treatment are crucial to improving the prognosis and reducing the mortality and unreasonable use of antibiotics.Because umbilical cord blood shares the same cell composition with fetal peripheral blood at the end of pregnancy, and has the advantages of easy availability and painlessness, many researchers have been devoted to exploring umbilical cord blood markers related to the diagnosis of EONS in recent years.Most studies suggest that umbilical cord blood culture, procalcitonin, C-reactive protein and interleukin-6 should be routinely used as single indicators for clinical diagnosis of EONS.The combination of two or more biomarkers may be more accurate for the diagnosis of EONS, which, however, needs to be confirmed with more trials, and it is also a significant direction of future research.In this article, progress in relevant research was reviewed in order to provide reference for early diagnosis of EONS.

Tubulointerstitial renal fibrosis is an essential feature of diabetic nephropathy (DN). Pericytes play a critical role in microvascular diseases and renal fibrogenesis. However, the role of pericytes in DN remains unclear. Herein, we aimed to explore the properties and possible mechanisms of pericytes in renal fibrosis in DN. Methods: We used multiplex immunofluorescence staining to evaluate the location and expression of activated pericytes and to assess capillary dilation and interstitial fibrosis in the kidneys of db/db mice. Pericytes were co-stained for alpha-smooth muscle actin (α-SMA) to determine which ones differentiate into myofibroblasts in db/db mice. Expression of CD34 and platelet-derived growth factor receptor beta (PDGFR-β) was assessed in kidney tissue from patients with DN by immunohistochemical staining. Results: We found that cell staining for nerve/glial antigen 2 (NG2)+ and PDGFR-β+ was greater in the kidneys of db/db mice than in those of db/m mice. There was impaired pericyte coverage of blood vessels and capillary dilation in the renal interstitium. These changes were accompanied by increased collagen I staining and an increase in the number of pericytes with profibrotic phenotypes, as identified by increased NG2+/PDGFR-β+/α-SMA+ and decreased NG2+/PDGFR-β+/α-SMA– staining. In DN patients, expression of PDGFR-β was stronger and there was loss of CD34 compared with the findings in control patients with minor glomerular lesions. Conclusion: In this study, we demonstrated that pericyte activation accompanied by peritubular capillary dysfunction and pericytemyofibroblast transition is associated with renal fibrosis in DN.

Purpose To investigating the pathological characteristics of the heart and spleen in a Kawasaki disease(KD)model induced by candida albicans watersoluble fraction(CAWS)and to provide a research basis for the pathological mechanisms of KD.Methods Intraperitoneal injection of CAWS was used to establish a KD model in C57BL/6 mice.Specimens of the heart,aorta,and spleen were collected to measure body weight and the weights of the heart and spleen.HE staining was utilized to examine the morphological alterations in the heart,aorta,and spleen.The expression levels of the ma-ture macrophage marker(F4/80),TNF-α,and IL-1β in the spleen were measured using qRT-PCR and immunofluorescence.its clinical pathological characteristics were analyze and relevant literatures were reviewed.Results Compared to the control group,there were no significant differences in the heart and body mass of the model group mice,but their spleen mass signif-icantly increased(P＜0.05).In the myocardial interstitium of model group mice,there was infiltration of mononuclear cells,disorder of the elastic fibers in the aortic wall along with mucoid degeneration,disruption of the splenic red and white pulp struc-ture,and significant macrophage infiltration.In the model group mice,the mRNA levels and immunofluorescence staining inten-sity of spleen F4/80(2.58-fold,P＜0.000 1),TNF-α(1.43-fold,P＜0.001),and IL-1β(3.62-fold,P＜0.000 1)were significantly higher than those in the control group.Conclusion Mice with KD models induced by CAWS can exhibit patholog-ical alterations akin to KD in the heart and aorta,significant en-largement of the spleen,infiltration by macrophages,with ele-vated expressions of TNF-α and IL-1β.

Objective:To establish the normal values of water-perfused high resolution esophageal manometry (HREM)(GAP-36A) at resting period, water swallowing, semisolid swallowing and solid swallowing in Chinese population.Methods:From September 1, 2019 to June 30, 2020, 91 healthy volunteers receiving water-perfused HREM (GAP-36A) at resting period, water swallowing, semisolid swallowing and solid swallowing were selected from 9 hospitals (Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; the First Affiliated Hospital of Dalian Medical University; the Second Hospital of Hebei Medical University; the Second Affiliated Hospital, Naval Medical University; the First Affiliated Hospital, Sun Yat-sen University; the First Affiliated Hospital, University of Science and Technology of China; Aviation General Hospital of China Medical University; the Affiliated Hospital of Medical School of Nanjing University and the First People′s Hospital of Yichang). Parameters included the position of the upper and lower edges of the upper esophageal sphincter (UES) and lower esophageal sphincter (LES), the length of the LES and UES, the position of the pressure inversion point (PIP), the resting pressure of UES and LES and swallow-related parameters such as the distal contraction integral (DCI), 4 s integrated relaxation pressure (IRP), distal latency (DL) and UES residual pressure. One-way analysis of variance, post-hoc test and sum rank test were used for statistical analysis.Results:A total of 87 healthy volunteers were enrolled, including 40 males and 47 females, aged (38.5±14.2) years old (ranged from 19 to 65 years old). The position of the upper and lower edges of the LES was (42.7±2.8) and (45.6±2.8) cm, respectively, the length of the LES was (2.9±0.4) cm, and the position of PIP was (43.3±2.8) cm. The position of the upper and lower edges of the UES was (18.1±3.0) and (22.6±2.0) cm, respectively, and the length of the UES was (4.8±1.0) cm. The resting pressure of LES and UES was (17.4±10.7) and (84.1±61.1) mmHg (1 mmHg=0.133 kPa), respectively. The DCI value at solid swallowing was higher than those at water swallowing and semisolid swallowing ((2 512.4±1 448.0) mmHg·s·cm vs. (2 183.2±1 441.2) and (2 150.8±1 244.8) mmHg·s·cm), and the differences were statistically significant ( t=-4.30 and -3.74, both P<0.001). The values of 4 s IRP at semisolid swallowing and solid swallowing were lower than that at water swallowing ((4.6±4.1) and (4.9±3.9) mmHg vs. (5.4±3.9) mmHg), and the differences were statistically significant ( t=3.38 and 2.09, P=0.001 and 0.037). The DL at water swallowing was shorter than those at semisolid swallowing and solid swallowing ((8.5±1.8) s vs. (9.8±2.2) and (10.6±2.8) s), and the DL at semisolid swallowing was shorter than that at solid swallowing, and the differences were statistically significant ( t=-10.21, -13.91 and -4.68, all P<0.001). The UES residual pressure at water swallowing was higher than those at semisolid swallowing and solid swallowing (9.5 mmHg, 6.5 to 12.3 mmHg vs. 8.0 mmHg, 4.5 to 11.7 mmHg and 5.5 mmHg, 2.0 to 9.3 mmHg), and the UES residual pressure at semisolid swallowing was higher than that at solid swallowing, and the differences were statistically significant ( t=3.48, 10.30 and 6.35, all P<0.001). Conclusions:The normal values of water-perfused HREM (GAP-36A) in Chinese population at resting period, water swallowing, semisolid swallowing and solid swallowing can provide a reference basis for clinical diagnosis and treatment for patients receiving water-perfused HREM examination.

Objective:To investigate the influencing factors of post-dialysis hypertension in maintenance hemodialysis (MHD) patients.Methods:This study was a cross-sectional and retrospective study. The patients receiving hemodialysis from January 9, 2017 to January 14, 2017 in 5 hemodialysis centers of Beijing area were selected. Post-dialysis hypertension was defined as an event characterized by an average increase of more than 15 mmHg in post-dialysis mean artery pressure (MAP) compared to intradialytic 3 h MAP during 3 consecutive hemodialysis sessions. Post-dialysis stable blood pressure was defined as an event characterized by an increase of less than 15 mmHg or a decrease of less than 10 mmHg in post-dialysis MAP compared to intradialytic 3 h MAP, with the exception of patients with post-dialysis hypertension and post-dialysis hypotension. The patients were divided into hypertension group and stable blood pressure group based on whether they had post-dialysis hypertension, and the differences of clinical data between the two groups were compared. The influencing factors of post-dialysis hypertension were analyzed by multivariate unconditional logistic regression.Results:A total of 491 MHD patients were enrolled in this study, including 65 patients (13.2%) in the hypertension group, 406 patients (82.7%) in the stable blood pressure group and 20 patients (4.1%) in the hypotension group. The age, blood calcium before dialysis and the proportion of patients using 1.75 mmol/L Ca 2+ dialysate in the hypertension group were higher than those of the stable blood pressure group, and pre-dialysis serum intact parathyroid hormone and pre-dialysis serum uric acid in the post hypertension group were lower than those of the stable blood pressure group (all P<0.05). The age, pre-dialysis serum intact parathyroid hormone, pre-dialysis serum calcium, pre-dialysis serum uric acid, dialysate Ca 2+ concentration of statistical differences between hypertension group and stable blood pressure group ( P<0.05), and post-dialysis serum calcium, pre-dialysis total serum cholesterol, application of β receptor blocker, gender of univariate analysis ( P<0.1) were included into the logistic regression equation as covariates. Multivariate logistic regression analysis showed that using 1.75 mmol/L Ca 2+ dialysate was the independent influencing factor of post-dialysis hypertension (with using 1.50 mmol/L Ca 2+ dialysate as reference, OR=2.930, 95% CI 1.282-6.694, P=0.011). The age and pre-dialysis serum calcium of statistical differences between hypertension group and stable blood pressure group ( P<0.05), and pre-dialysis serum sodium and pre-dialysis serum uric acid of univariate analysis ( P<0.1) were included into the logistic regression equation as covariates. The older age ( OR=1.046, 95% CI 1.000-1.093, P=0.049) and higher pre-dialysis serum calcium ( OR=21.847, 95% CI 2.111-226.075, P=0.010) were the independent influencing factors of post-dialysis hypertension when the 1.50 mmol/L Ca 2+ dialysate was used. Conclusions:The independent influencing factor of post-dialysis hypertension is using 1.75 mmol/L Ca 2+ dialysate, while the independent influencing factors of post-dialysis hypertension are the older age and the higher pre-dialysis serum calcium level when the dialysate Ca 2+ concentration was 1.50 mmol/L.