Skin wound healing tends to slow down with aging, which is detrimental to both minor wound recovery in daily life and the recovery after surgery. The aim of current study was to explore the effect of histone deacetylase 6 (HDAC6) on wound healing during aging. Cultured human dermal fibroblasts (HDFs) and mouse full-thickness skin wound model were used to explore the functional changes of replicative senescent dermal fibroblasts and the effect of aging on skin wound healing. Scratch wound healing assay revealed significantly decreased migration speed of senescent HDFs, and BrdU incorporation assay indicated their considerably retardant proliferation. The protein expression levels of collagen and HDAC6 were significantly decreased in both senescent HDFs and skin tissues from aged mice. HDAC6 activity inhibition with highly selective inhibitor tubastatin A (TsA) or HDAC6 knockdown with siRNA decreased the migration speed of HDFs and considerably suppressed fibroblast differentiation induced by transforming growth factor-β1 (TGF-β1), which suggests the involvement of HDAC6 in regulating fundamental physiological activities of dermal fibroblasts. In vivo full-thickness skin wound healing was significantly delayed in young HDAC6 knockout mice when compared with young wild type mice. In addition, the wound healing was significantly slower in aged wild type mice than that in young wild type mice, and became even worse in aged HDAC6 knockout aged mice. Compared to the aged wild type mice, aged HDAC6 knockout mice exhibited delayed angiogenesis, reduced collagen synthesis, and decreased collagen deposition in skin wounds. Together, these results suggest that delayed skin wound healing in aged mice is associated with impaired fibroblast function. Adequate expression and activity of HDAC6 are required for fibroblasts migration and differentiation.
Humans ; Animals ; Mice ; Aged ; Histone Deacetylase 6 ; Skin ; Wound Healing ; Cell Movement ; Collagen/pharmacology* ; Fibroblasts ; Mice, Knockout ; Cells, Cultured

Echinococcosis is a zoonotic parasitic disease caused by Echinococcus infections, and this disorder may cause fibrosis of multiple vital organs, which may further progress into cirrhosis. Early-stage hepatic fibrosis is reversible, and unraveling the mechanisms underlying hepatic fibrosis induced by Echinococcus infections is of great significance for the prevention and treatment of early-stage hepatic fibrosis. Recently, the studies pertaining to hepatic fibrosis associated with Echinococcus infections focus on cytokines and immune cells. This review summarizes the advances in the mechanisms underlying host immune cells- and cytokines-mediated hepatic fibrosis in humans or mice following Echinococcus infections.

Objective:To study the trends and ranges of blood pressure in extremely premature infants (EPIs) during the first 7 days after birth.Methods:From January 2016 to December 2020, EPIs born in our hospital were retrospectively analyzed. Their blood pressure were monitored using umbilical arterial catheters and no patients needed anti-hypotension treatment. The clinical data of the infants and their mothers, blood pressure data during the first 7 days after birth, clinical outcomes and complications were collected. The trends of blood pressure in untreated EPIs were analyzed and the blood pressure ranges of EPIs of different gestational ages (GA) were established.Results:A total of 145 cases of EPIs were included and their systolic pressure, diastolic pressure and mean blood pressure showed upward trends during 2~168 h after birth ( P<0.001). The diastolic pressure increased significantly within 24 h after birth ( P<0.05), systolic pressure and mean blood pressure increased significantly within 72 h after birth ( P<0.05). Blood pressure increased with age and GA. Conclusions:The blood pressure of EPIs will increase spontaneously during 7 days after birth. The ranges of blood pressure are measured for infants with different GA to provide clinical evidence for blood pressure management of EPIs during early postnatal period.

BACKGROUND: Vascular endothelial dysfunction is considered a key pathophysiologic process for the development of acute lung injury. In this study, we aimed at investigating the effects of unfractionated heparin (UFH) on the lipopolysaccharide (LPS)-induced changes of vascular endothelial-cadherin (VE-cadherin) and the potential underlying mechanisms. METHODS: Male C57BL/6 J mice were randomized into three groups: vehicle, LPS, and LPS + UFH groups. Intraperitoneal injection of 30 mg/kg LPS was used to induce sepsis. Mice in the LPS + UFH group received subcutaneous injection of 8 U UFH 0.5 h before LPS injection. The lung tissue of the mice was collected for assessing lung injury by measuring the lung wet/dry (W/D) weight ratio and observing histological changes. Human pulmonary microvascular endothelial cells (HPMECs) were cultured and used to analyze the effects of UFH on LPS- or tumor necrosis factor-alpha (TNF-α)-induced vascular hyperpermeability, membrane expression of VE-cadherin, p120-catenin, and phosphorylated myosin light chain (p-MLC), and F-actin remodeling, and on the LPS-induced activation of the phosphatidylinositol-3 kinase (PI3K)/serine/threonine kinase (Akt)/nuclear factor kappa-B (NF-κB) signaling pathway. RESULTS: In vivo, UFH pretreatment significantly attenuated LPS-induced pulmonary histopathological changes (neutrophil infiltration and erythrocyte effusion, alveolus pulmonis collapse, and thicker septum), decreased the lung W/D, and increased protein concentration (LPS vs. LPS + UFH: 0.57 ± 0.04 vs. 0.32 ± 0.04 mg/mL, P = 0.0092), total cell count (LPS vs. LPS + UFH: 9.57 ± 1.23 vs. 3.65 ± 0.78 × 10/mL, P = 0.0155), polymorphonuclear neutrophil percentage (LPS vs. LPS + UFH: 88.05% ± 2.88% vs. 22.20% ± 3.92%, P = 0.0002), and TNF-α (460.33 ± 23.48 vs. 189.33 ± 14.19 pg/mL, P = 0.0006) in the bronchoalveolar lavage fluid. In vitro, UFH pre-treatment prevented the LPS-induced decrease in the membrane expression of VE-cadherin (LPS vs. LPS + UFH: 0.368 ± 0.044 vs. 0.716 ± 0.064, P = 0.0114) and p120-catenin (LPS vs. LPS + UFH: 0.208 ± 0.018 vs. 0.924 ± 0.092, P = 0.0016), and the LPS-induced increase in the expression of p-MLC (LPS vs. LPS + UFH: 0.972 ± 0.092 vs. 0.293 ± 0.025, P = 0.0021). Furthermore, UFH attenuated LPS- and TNF-α-induced hyperpermeability of HPMECs (LPS vs. LPS + UFH: 8.90 ± 0.66 vs. 15.84 ± 1.09 Ω·cm, P = 0.0056; TNF-α vs. TNF-α + UFH: 11.28 ± 0.64 vs. 18.15 ± 0.98 Ω·cm, P = 0.0042) and F-actin remodeling (LPS vs. LPS + UFH: 56.25 ± 1.51 vs. 39.70 ± 1.98, P = 0.0027; TNF-α vs. TNF-α + UFH: 55.42 ± 1.42 vs. 36.51 ± 1.20, P = 0.0005) in vitro. Additionally, UFH decreased the phosphorylation of Akt (LPS vs. LPS + UFH: 0.977 ± 0.081 vs. 0.466 ± 0.035, P = 0.0045) and I kappa B Kinase (IKK) (LPS vs. LPS + UFH: 1.023 ± 0.070 vs. 0.578 ± 0.044, P = 0.0060), and the nuclear translocation of NF-κB (LPS vs. LPS + UFH: 1.003 ± 0.077 vs. 0.503 ± 0.065, P = 0.0078) in HPMECs, which was similar to the effect of the PI3K inhibitor, wortmannin. CONCLUSIONS The protective effect of UFH against LPS-induced pulmonary endothelial barrier dysfunction involves VE-cadherin stabilization and PI3K/Akt/NF-κB signaling.

Aortic Valve ; Aortic Valve Insufficiency ; Heart Septal Defects, Ventricular/surgery* ; Humans

OBJECTIVETo observe the effect of Schistosoma japonicum cysteine protease inhibitor (rSjCystatin) for treatment of lipopolysaccharide (LPS)-induced sepsis in mice.

METHODSAfter a week of adaptive feeding, 54 BALB/c mice were randomly divided into normal control group (group A), sepsis group (group B), and rSjCystatin intervention group (group C). The mice in group A received an intraperitoneal injection of PBS (100 µL), and those in groups B and C were injected with PBS (100 µL) containing LPS (10 mg/kg); the mice in group C were also intraperitoneally injected with 25 µg sjCystatin in 100 µL PBS 30 min after LPS injection. From each group, 10 mice were randomly selected 24 h after PBS or LPS injection for detecting serum levels of TNF-α, IL-6, and IL-10 using ELISA and the levels of ALT, AST, BUN, and Cr using automatic biochemical analyzer; the pathological changes in the liver, lung and kidney were observed with HE staining. The remaining 8 mice in each group were used for observing the changes in the general condition and the 72-h survival.

RESULTSThe 72-h survival rates of the mice was 100% in group A, 0 in group B, and 36% in group C, showing a significant difference among the 3 groups (P<0.05). Compared with those in group A, the mice in group B exhibited obvious liver, lung, and renal pathologies with increased levels of ALT, AST, BUN, Cr, IL-6, and TNF-α (P<0.05). Treatment with sjCystatin significantly lessened LPS-induced organ pathologies, lowered the levels of liver and renal functional indexes and the pro-inflammatory cytokines, and increased the serum level of IL-10 in the mice (P<0.05).

CONCLUSIONSjCystatin can produce a significant therapeutic effect on sepsis induced by LPS in mice.

The present study was designed to determine the chemical constituents of the stem tuber of Pinellia pedatisecta. The chemical constituents were isolated and purified by various chromatographic techniques, and their structures were elucidated on the basis of physicochemical properties and spectral data. Three new alkaloids (compounds 1, 2, and 3) were obtained and identified as 9-((5-methoxypyridin-2-yl)methyl)-9H-purin-6-amine (1), 4-(2-(2, 5-dioxopyrrolidin-1-yl)ethyl)phenyl acetate (2), and N-(9-((5-methoxypyridin-2-yl)methyl)-9H-purin-6-yl)acetamide (3). These compounds were evaluated for their cytotoxicity against human cervical cancer HeLa cells. Compounds 1 and 3 significantly inhibited the proliferation of HeLa cells with IC values being 3.02 ± 0.54 and 7.16 ± 0.62 μmol·L, respectively.
Alkaloids ; chemistry ; isolation & purification ; pharmacology ; Cell Proliferation ; drug effects ; HeLa Cells ; Humans ; Pinellia ; chemistry ; Plant Extracts ; chemistry ; isolation & purification ; pharmacology ; Plant Stems ; chemistry ; Plant Tubers ; chemistry

Objective To investigate the relationship between preoperative abnormal transthoracic echocardiogram (TTE) and postoperative major adverse cardiac events (MACE) in patients undergoing non-cardiac surgery.Methods This study was a nested case control study.Patients who underwent elective non-cardiac surgery in Peking University First Hospital from November 15,2012 to January 15,2013 were enrolled.We screened patients who received preoperative TTE examination from electrical medical record.The primary outcome of this study was the incidence of postoperative MACEs.The patients were divided into MACE group and control group depending on if they suffered MACE.For each patient in MACE group,4 patients without MACE events were selected for control group in term of two criteria:same revised cardiac risk index and same type of surgery.Related perioperative data were collected.Multivariate logistic analysis was used for screening potential risk factors related to MACE.Results During the study period,a total of 2975 patients undergoing elective surgery,2081 met the inclusion criteria.Amongst these patients,530 patients received preoperative TTE examinations and 25 suffered postoperative MACEs.Overall incidence of TTE abnormalities was 91.9％(487/530).25 patients with MACE and 100 patients without MACE (as control group) were selected for case control analysis.The incidence of TTE abnormality was about 92.0％ (23/25) in MACE group and 93.0％(93/100) in control group (OR=0.866,95％CI 0.169-4.446,P=1.000).Multivariate logistic analysis showed that left ventricular hypertrophy was an independent risk of MACE (OR=4.324,95％CI 1.320-14.160,P=0.016),female(OR=4.782,95％CI 1.636-13.980,P=0.005) and history of chronic renal failure (OR=21.952,95％CI 1.547-311.475,P=0.016) were also related with MACE.The predictive value of preoperative TTE abnormality against MACE was very low in ROC analysis (AUC=0.501,P=0.992).Conclusions Left ventricular hypertrophy is related to increased risk of postoperative MACE.However,further studies are needed to confirm the value of TTE examination as a routine examination for cardiac evaluation before surgery.

OBJECTIVE: To investigate the incidence of peri-anesthesia allergy in a tertiary teaching hospital. METHODS: This was a retrospective cohort study. Patients who received anesthesia in operation rooms at Peking University First Hospital from January 2012 to April 2017 were enrolled. Researchers reviewed all the patients' electronic records and screened suspect allergy cases. Allergy was diagnosed according to the definition in Consensus on Management of Perioperative Allergy (China) and Scandinavian Clinical Practice Guidelines on the Diagnosis, Management and Follow-up of Anaphylaxis during Anesthesia. After obtaining the electronic records, two researchers began to screen and supplement missing data according medical records independently, then they checked out each other's data. The final data were reviewed by another two researchers. We collected the patients' basic characteristics, surgery type, anesthesia type, peri-anesthesia use of drugs, prognosis and other data. Univariate logistic regression was employed to screen potential factors of allergy. Factors with statistical significance (P<0.05) in univariate Logistic regression were entered into multivariate Logistic regression to identify independent risk factors of allergy. RESULTS: In the study, 106 074 patients entered final statistic analysis. The incidence of peri-anesthesia allergy was about 1.5/1 000 (156/106 074). The incidence of Grades I, II and III allergy was 64.1% (100/156), 30.1% (47/156), and 5.8% (9/156) respectively. Multivariate logistic regression showed 5 independent risk factors of allergy including history of allergy (OR=6.836, 95%CI: 4.461-10.474, P<0.001), intraoperative use of sufentanil (OR=1.993, 95%CI: 1.228-3.232, P=0.005), intraoperative use of cis-atracuronium (OR=2.495, 95%CI: 1.599-3.893, P<0.001), intraoperative infusion of antibiotics (OR=2.005, 95%CI: 1.375-2.924, P<0.001) and frozen fresh plasma (OR=3.055, 95%CI: 1.842-5.068, P<0.001). CONCLUSION The incidence of peri-anesthesia allergy is high and further attempt is needed to establish standard operation process of diagnosis and treatment of allergy.
Anaphylaxis/chemically induced* ; Anesthesia ; Anesthetics/adverse effects* ; China ; Drug Hypersensitivity ; Humans ; Retrospective Studies ; Risk Factors ; Surveys and Questionnaires

Objective:This study aimed to assess serum fibulin-3 levels in patients with colon cancer compared with healthy controls and its relationship to demographics and tumor pathology.Methods:A total of 97 patients (mean age,59.6 years;57.7％ males) with colon cancer and 86 controls (mean age,58.8 years;54.7％ males) were included.Serum levels of fibulin-3 were determined using a commercially available sandwich ELISA (Enzyme-Linked ImmunoSorbent Assay).Results:Preoperative serum fibulin-3 levels were significantly lower in the group of patients with colon cancer(39.86 ± 24.37) ng/mL compared with the control group (94.25 ± 31.28) ng/mL.Preoperative fibulin-3 levels and negatively correlated with the degree of tumor TNM stage (P＜0.05),fibulin-3 levels gradually decreased by tumor stage from Ⅰ to Ⅳ and the difference is statistically significant.The serum fibulin-3 levels were correlated significantly with tumor size,lymph node metastasis,distant metastasis and CEA levels(P＜0.05).Conclusion:It was concluded that fibulin-3 is expressed at a lower level in colon cancer,and it is significant correlated with tumor burden,decreased level of fibulin-3 can serve as a marker for advanced colon cancer.