OBJECTIVE To investigate the effect of Jiawei Tianwang Buxin Dan(JWBXD)on insomnia in rats exposed to simulated high-altitude conditions.METHODS ① Thirty SD rats were randomly divided into the normal control,model,model+Jiawei Tianwang Buxin Dan(JWBXD,9.6 mg·kg-1),model+Tianwang Buxin Dan(TWBXD,9.6 mg·kg-1),and model+diazepam(DZP,3 mg·kg-1)groups.Rats,except for the normal control group,were subjected to a low-pressure,low-oxygen animal experimental chamber simulating a 5000 m altitude.Respective drugs were ig administrated once daily at 9:00 for seven days,and signal acquisition and sleep analysis were conducted by a wireless physiological sig-nal telemetry system.②Forty rats were randomly divided into five groups as described in ①.Through-out the experiment,the general condition and body mass of the rats were observed daily.Drug adminis-tration lasted for seven days,and grip strength was tested one hour after the final administration.ELISA was used to measure the levels of corticotropin-releasing hormone(CRH),adrenocorticotropic hor-mone(ACTH),corticosterone(CORT),and melatonin(MLT)in serum.Western blotting was performed to measure the expression levels of core clock proteins period circadian regulator 2(Per2),circadian locomotor output cycles(Clock),cryptochrome 2(Cry2),brain-muscle arnt-like protein 1(Bmal1),nuclear receptor subfamily 1,group D member 1(NR1D1),glycogen synthase kinase-3β(GSK-3β),as well as acetylserotonin O-methyltransferase(ASMT)in the hypothalamus and pineal gland,respectively.RESULTS ① Compared with the normal control group,the model group exhibited a decrease in total sleep time(P<0.01),an increase in wakefulness(P<0.01),a significant reduction in slow wave sleep(SWS)(P<0.05)and the mean bouts duration(P<0.05).Compared with the model group,both DZP and JWBXD(P<0.01)prolonged sleep time and suppressed wakefulness(P<0.01)in the hypoxic envi-ronment.DZP and JWBXD prolonged SWS(P<0.05,P<0.01),while TWBXD had no significant effect.JWBXD improved the mean bouts duration of SWS in the model rats(P<0.01),whereas no such improvement was observed in model+DZP and model+TWBXD groups.② Compared with the normal control group,the model group showed a significant decrease in forelimb grip strength(P<0.01),increased levels of serum ACTH(P<0.05),CRH,and CORT(P<0.01),and decreased MLT levels(P<0.05).The expression levels of Per2,Cry2,GSK-3β,and NR1D1 in the hypothalamus were downregu-lated(P<0.05,P<0.01),while Bmal1 and Clock were upregulated(P<0.05,P<0.01).ASMT expression in the pineal gland was decreased(P<0.05).Compared with the model group,JWBXD and TWBXD enhanced forelimb grip strength(P<0.01),reduced serum CORT and ACTH levels(P<0.05),decreased CRH levels(P<0.01),and restored MLT levels(P<0.01).JWBXD upregulated the expression levels of Per2,Cry2,GSK-3β and NR1D1 in the hypothalamus(P<0.05,P<0.01),but downregulated Bmal1 and Clock expression(P<0.05,P<0.01).TWBXD downregulated Bmal1 expression in the hypothalamus(P<0.01)and increased NR1D1 expression(P<0.05).DZP significantly enhanced the expression levels of Per2,Cry2 and NR1D1 in the hypothalamus(P<0.01).JWBXD,TWBXD and DZP improved ASMT expression in the pineal gland(P<0.05).CONCLUSION JWBXD can improve sleep structure and prolong the duration of SWS in rats exposed to simulated high-altitude conditions.The mechanisms may involve the regulation of core clock protein expressions in the hypothalamus,promotion of mela-tonin secretion,and inhibition of HPA axis hyperactivity.

Objective:Hepatic fibrosis is a common pathological basis for many chronic liver diseases and can progress to cirrhosis,a leading cause of mortality in liver diseases.Early identification and reversal of hepatic fibrosis are key in the treatment of chronic liver disease.This study aims to compare the expression levels of serum core fucosylated low molecular weight kininogen(LMWK-Fc)and alpha-galactosylated(α-Gal)antibodies in patients with hepatic fibrosis at different stages,and to evaluate their diagnostic efficacy for hepatic fibrosis. Methods:A retrospective analysis was conducted on 275 patients with chronic liver disease who visited the Department of Infectious Diseases at the Second Xiangya Hospital of Central South University between June 2022 and March 2023.Among these,115 patients underwent liver biopsy.Based on the extent of collagen deposition and its impact on liver structure and microcirculation,patients were staged from 0 to 4:S0(no significant collagen deposition in liver tissues;liver structure and microcirculation are normal),S1(mild collagen deposition in liver tissues,with partial disruption of lobule structure,but microcirculation remains largely normal),S2(moderate collagen deposition in liver tissues,with partial disruption of lobule structure and microcirculation),S3(extensive collagen deposition in liver tissues,with substantial disruption of lobule structure and microcirculation),and S4(development of cirrhosis,with heavy collagen deposition,complete disruption of lobule structure,and severe impairment of microcirculation).Patients were grouped as no fibrosis(S0),fibrosis(S1-S2),and significant fibrosis(S3-S4).For the 160 patients without liver biopsy,they were categorized based on liver stiffness measurement(LSM)value:no fibrosis(F0:LSM＜7.3 kPa),fibrosis(F1-F2:LSM 7.3-12.4 kPa),and significant fibrosis(F3-F4:LSM＞12.4 kPa).Demographic data(age,gender)and laboratory indicators(alanine transaminase,aspartate transaminase,gamma-glutamyl transferase,alkaline phosphatase,alpha-fetoprotein,platelet count)were collected to calculate the fibrosis-4 index(FIB-4)and aspartate aminotransferase-to-platelet ratio index(APRI).Serum LMWK-Fc and α-Gal antibodies were measured and compared across the groups,and their correlation with fibrosis severity was analyzed.The receiver operating characteristic(ROC)curve was used to assess the predictive value of serum LMWK-Fc and α-Gal antibody levels for hepatic fibrosis. Results:Among the 160 patients without complete liver biopsy,serum α-Gal antibody and LMWK-Fc levels increased progressively from the no fibrosis group to the significant fibrosis group,with statistically significant differences(P＜0.05).Among the 115 patients with liver biopsy,serum LMWK-Fc levels were significantly higher in the fibrosis group and the significant fibrosis groups compared with the no fibrosis group,and α-Gal antibody levels were significantly higher in the significant fibrosis group compared with the no fibrosis group and the fibrosis group(P＜0.001,P=0.032,respectively).Univariate and multivariate linear regression analyses showed that hepatic fibrosis was correlated with gender and LMWK-Fc levels(both P＜0.05),but not with age,α-Gal antibody levels,FIB-4,or APRI(all P＞0.05). Conclusion:The expression levels of serum LMWK-Fc and α-Gal antibodies vary across different stages of hepatic fibrosis,suggesting a potential association with fibrosis progression.LMWK-Fc levels have a certain predictive value for the diagnosis of hepatic fibrosis.

Catheter associated urinary tract infection (CAUTI) refer to urinary system infections that occur after the insertion of a urinary catheter or within 48 hours after its removal. CAUTI exacerbate patient conditions, prolong hospital stays, increase medical costs and economic burdens on patients, and can be life-threatening in severe cases. The Asia Pacific Society of Infection Control (APSIC) convened a working group of infection prevention and control experts from the Asia-Pacific region to publish the APSIC guideline for prevention of catheter associated urinary tract infections (CAUTIs) (referred to as the "APSIC Guideline"). This guideline encompasses the prevention and management of CAUTI in patients with indwelling catheters, covering the entire process from catheter insertion, maintenance, to removal, and are characterized by their practicability and directive nature. This article interprets the APSIC Guideline from aspects such as risk factors of CAUTI, diagnosis, development of prevention strategies, monitoring, and implementation of prevention plans, aiming to provide scientific guidance for clinical healthcare professionals in preventing CAUTI.

OBJECTIVE: To investigate time-related association between fluid balance and prognosis in sepsis patients. METHODS: A retrospective cohort study was conducted based on the data of sepsis patients in the Medical Information Database for Intensive Care-IV 2.0 (MIMIC-IV 2.0) from 2008 to 2019. Sepsis patients aged ≥ 18 years who were admitted to intensive care unit (ICU) for at least 2 days were included. The daily fluid balance and cumulative fluid balance (CFB) were calculated from days 1 to 7 after ICU admission. According to CFB,the patients were divided into negative fluid balance group (CFB% < 0%), fluid balance group (0% ≤ CFB% ≤ 10%), and fluid overload group (CFB% > 10%). In-hospital mortality was the primary outcome. Multifactorial Logistic regression was used to analyze time-related association between different CFB and the risk of in-hospital mortality in patients with sepsis during 7 days after ICU admission. In addition, subgroup analysis was performed on patients with septic shock and patients with sepsis who stayed in the ICU for 7 days or longer. RESULTS: A total of 11 437 patients with sepsis were included, of which 6 595 were male and 4 842 were female. The mean age was (64.4±16.4) years. A total of 10 253 patients (89.6%) survived and 1 184 patients (10.4%) died during hospitalization. Compared with the survival group, patients in the death group were older, lighter, had higher sequential organ failure assessment (SOFA), simplified acute physiology score II (SAPS II), longer ICU stay, higher incidence of septic shock, and higher proportion of invasive mechanical ventilation, renal replacement therapy (RRT) and vasoactive drugs. In terms of comorbidities, congestive heart failure, renal disease, liver disease, and malignancy were more common in the death group. The death group had a higher daily fluid balance than the survival group during 7 days after ICU admission, the CFB in the two groups gradually increased with length of ICU stay. After adjusting variables such as age, gender, race, SOFA score, SAPS II score, comorbidities, and the use of invasive mechanical ventilation, RRT and vasoactive drugs, multivariate Logistic regression analysis showed that fluid overload on day 1 after ICU admission was a protective factor for the reduced risk of in-hospital mortality in sepsis patients [odds ratio (OR) = 0.74, 95% confidence interval (95%CI) was 0.64-0.86, P = 0.001]. However, fluid overload on day 3 was a risk factor for in-hospital mortality in sepsis patients (OR = 1.70, 95%CI was 1.47-1.97, P < 0.001) and the risk of in-hospital mortality was significantly increased from day 4 to day 7. Furthermore, the same results were obtained in patients with septic shock and sepsis patients who stayed in the ICU for 7 days or longer. CONCLUSIONS Fluid overload on day 1 was associated with reduced in-hospital mortality. However, from the third day, fluid overload increases the risk of in-hospital mortality. Thus, managing fluid balance at different times may improve prognosis.
Humans ; Male ; Female ; Middle Aged ; Aged ; Aged, 80 and over ; Shock, Septic ; Cohort Studies ; Retrospective Studies ; Sepsis ; Intensive Care Units ; Water-Electrolyte Balance ; Heart Failure ; Prognosis

Objective To investigate the prevalence of hepatitis D virus (HDV) infection among patients with chronic hepatitis B virus (HBV) infection in some regions of China. Methods Serum samples were collected from 3 131 patients with chronic HBV infection in 10 provinces, cities, and autonomous regions of China from March 2021 to June 2022, and anti-HDV IgG ELISA was used for the detection of all serum samples. Nested reverse transcription-polymerase chain reaction (nRT-PCR) was used to detect HDV RNA in anti-HDV IgG-positive samples, and the nRT-PCR amplification products of HDV RNA-positive samples were sequenced and analyzed to determine HDV genotype. The clinical features of anti-HDV IgG-positive patients were analyzed. The Mann-Whitney U rank sum test was used for comparison of continuous data between two groups, and the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups. Results The positive rate of anti-HDV IgG in the 3 131 patients with chronic HBV infection was 0.70% (22/3 131), and that in the patients with chronic HBV infection in Inner Mongolia Autonomous Region, Xinjiang Uygur Autonomous Region, Beijing, and Hunan Province was 1.81% (16/886), 0.88% (2/226), 0.28% (2/708), and 1.00% (2/200), respectively; the patients with chronic HBV infection in Inner Mongolia Autonomous Region had a significantly higher positive rate of anti-HDV IgG than those in Beijing ( P =0.004), and there was no significant difference between the other regions ( P > 0.05). Clinical features of the patients with chronic HBV infection in Inner Mongolia Autonomous Region showed that compared with the anti-HDV IgG-negative group, the anti-HDV IgG-positive group had a significantly higher proportion of patients with Mongol nationality ( P =0.001), abnormal alanine aminotransferase ( P =0.007), or antiviral treatment ( P =0.029), as well as a significantly lower median HBV DNA level ( P =0.030). A total of 19 HDV RNA-positive samples were identified, all of which had HDV genotype 1. Conclusion The prevalence rate of HDV varies greatly across different regions of China, with a higher prevalence rate of HDV in patients with chronic HBV infection from Inner Mongolia Autonomous Region. HDV genotype 1 is the predominant genotype in some provinces and cities of northern China.

Central nervous system (CNS) injuries, including stroke, traumatic brain injury, and spinal cord injury, are essential causes of death and long-term disability and are difficult to cure, mainly due to the limited neuron regeneration and the glial scar formation. Herein, we apply extracellular vesicles (EVs) secreted by M2 microglia to improve the differentiation of neural stem cells (NSCs) at the injured site, and simultaneously modify them with the injured vascular targeting peptide (DA7R) and the stem cell recruiting factor (SDF-1) on their surface via copper-free click chemistry to recruit NSCs, inducing their neuronal differentiation, and serving as the nanocarriers at the injured site (Dual-EV). Results prove that the Dual-EV could target human umbilical vascular endothelial cells (HUVECs), recruit NSCs, and promote the neuronal differentiation of NSCs in vitro. Furthermore, 10 miRNAs are found to be upregulated in Dual-M2-EVs compared to Dual-M0-EVs via bioinformatic analysis, and further NSC differentiation experiment by flow cytometry reveals that among these miRNAs, miR30b-3p, miR-222-3p, miR-129-5p, and miR-155-5p may exert effect of inducing NSC to differentiate into neurons. In vivo experiments show that Dual-EV nanocarriers achieve improved accumulation in the ischemic area of stroke model mice, potentiate NSCs recruitment, and increase neurogenesis. This work provides new insights for the treatment of neuronal regeneration after CNS injuries as well as endogenous stem cells, and the click chemistry EV/peptide/chemokine and related nanocarriers for improving human health.

Objective:To explore the value of video-electroencephalography (VEEG) combined with amplitude-integrated electroencephalography (aEEG) in evaluating the condition and prognosis of neonatal hyperbilirubinemia brain injuries.Methods:A total of 120 children with hyperbilirubinemia treatedin the Central Hospital of Enshi Tujia and Miao Autonomous Prefecture from July 2019 to July 2020 were enrolled. According to MRI with or without T 1 weighted imging (T 1WI) hyperintensity changes in the globus pallidus, they were divided into the brain injury group (52 cases) and the normal group(68 cases). According to the severity of brain injury, the brain injury group was divided into bilirubin encephalopathy group (23 cases) and subclinical bilirubin brain injury group (29 cases). According to the scores of Gesell Development Scale, the brain injury group was divided into good prognosis group (37 cases)and poor prognosis group (15 cases). The diagnostic value in brain injury with hyperbilirubinemia, the evaluation of the severity of brain injury and the predictive value of VEEG and aEEG were analyzed. Results:The abnormal rates of VEEG and aEEG in the brain injury group were higher than those in the normal group: 76.92% (40/52) vs. 8.82% (6/68), 80.77% (42/52) vs. 11.76% (8/68), the differences were statistically significant ( χ2 = 57.81 and 57.73, P<0.01). The abnormal rates of VEEG and aEEG in bilirubin encephalopathy group were higher than those in subclinical bilirubin brain injury group: 91.30% (21/23) vs. 65.52% (19/29), 95.65% (22/23) vs. 68.97% (20/29), the differences were statistically significant ( χ2 = 4.80 and 5.88, P<0.05). There was no significant difference in abnormal rates of VEEG and aEEG between the good prognosis group and poor prognosis group ( P>0.05). The results of operating characteristic curve analysis showed that the areas under the curve of VEEG combined with aEEG in the diagnosis of brain injury with hyperbilirubinemia, evaluation of the severity of brain injury, predicting the prognosis of children were higher than those of each examination method used alone ( P<0.05). Conclusions:VEEG combined with aEEG has diagnostic value for neonatal brain injury with hyperbilirubinemia, and has evaluation value for severity and prognosis of the disease.

Objective:To investigate the expression of high mobility group protein 1 (HMGB1) and interleukin-17 (IL-17) in peripheral blood and membrane tissues of pregnant women with premature rupture of membranes (PROM) and its relationship with intrauterine infection.Methods:Seventy-four pregnant women with PROM from January 2019 to June 2021 were selected as the study group, and 58 healthy pregnant women at the corresponding period were selected as the healthy control group. The levels of HMGB1 and IL-17 in peripheral blood and membrane tissues and serum CD 8+ were compared between the two groups. The pregnant women with PROM were divided into the chorioamnionitis group, subclinical chorioamnionitis group and normal group according to their intrauterine infection, the expression levels of HMGB1 and IL-17 in peripheral blood and membrane tissues of patients with different infection degrees were compared, and the correlation with the severity of intrauterine infection were analyzed. Results:The levels of peripheral blood HMGB1, membrane tissues HMGB1, peripheral blood IL-17, membrane tissues IL-17 and serum CD 8+ in the study group were higher than those in the control group: (28.34 ± 5.16) μg/L vs. (22.51 ± 4.09) μg/L, 0.79 ± 0.12 vs. 0.34 ± 0.05, (13.05 ± 2.57) ng/L vs. (8.16 ± 1.38) ng/L, 0.37 ± 0.06 vs. 0.12 ± 0.02, 0.386 ± 0.052 vs. 0.252 ± 0.044, there were statistical differences ( P<0.05). The levels of HMGB1 and IL-17 in peripheral blood and membrane tissues and serum CD 8+ were increased with the severity of severity of intrauterine infection ( P<0.05). The results of Spearman correlation analysis showed that the level of peripheral blood HMGB1, membrane tissues HMGB1 and IL-17 had positively correlated with the severity of intrauterine infection ( r = 0.336, 0.316, 0.311, P<0.05). The results of receiver operating characteristic curve analysis showed that combined detection of HMGB1 and IL-17 levels in peripheral blood and membrane tissues and serum CD 8+ levels in evaluating the severity of intrauterine infection had higher area under the curve than that of each index alone ( P<0.05). Conclusions:Pregnant women with PROM have abnormal HMGB1 and IL-17 levels in peripheral blood and membrane tissues, and HMGB1 levels in peripheral blood and mRNA expressions of HMGB1 and IL-17 in membrane tissues are positively correlated with the severity of intrauterine infection, which has evaluation value for the severity of the disease.

Sarcopenia, characterized as the progressive decrease in skeletal muscle mass, strength, and function, has been becoming one of chronic musculoskeletal diseases in aging people. In basic research studies, a reliable experimental model would be vital significance for deeply understanding pathophysiological mechanism of sarcopenia and developing novel drugs. This review provided a preliminary summary on the potential mechanisms involved in senescence-induced sarcopenia, followed by a discussion on research progress on pharmacology models based on molecular mechanism of senescence, especially from in vitro cell models and in vivo animal models.

Objective: To investigate the effects of embryonic inflammation on the hippocampal synaptosomal-associated protein 25(SNAP-25) level and cognitive function in middle-aged. Methods: During gestational days 15-17, the CD-1 maternal mice received a daily intraperitoneal injection of lipopolysaccharides(LPS, 50 μg/kg) or the equal volume of normal saline, and the corresponding offspring were regarded as LPS group and CON group respectively. At the age of young(3-month-old) and middle-aged(15-month-old), the spatial learning and memory ability was assessed using Morris water maze(MWM), and the expression of hippocampal SNAP-25 protein was detected by immunohistochemical method and Western blot. Results: Compared with the 3-month CON group, the 15-month CON group had longer swimming distance(P<0.01), lower swimming distance percentage(P<0.01) in the target quadrant, and higher hippocampal subregions(CA1, CA3, DG) SNAP-25 levels(P<0.01). The same results were obtained in 15-month LPS group compared with 15-month CON group in learning and memory phase(P<0.05), and higher hippocampal subregions(CA1, DG) SNAP-25 levels(P<0.01). Pearson correlation analysis indicated that the hippocampal CA1 and CA3 subregions SNAP-25 level was positively correlated with the swimming distance, but negatively correlated with the percentage of swimming distance in the target quadrant. Conclusion Embryonic inflammation can accelerate the impairment of spatial learning and memory and the increase of hippocampal CA1 and CA3 subregions SNAP-25 protein in middle-aged CD-1 mice, and there may be a correlation between them.