Use of the Serum Level of Cholinesterase as a Prognostic Marker of Nonfatal Clinical Outcomes in Patients Hospitalized with Acute Exacerbations of Chronic Obstructive Pulmonary Disease.

Introduction: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) contributes to a poor prognosis. Reliable biomarkers to predict adverse outcomes during hospitalization are important. Aim: To investigate the relationship between the serum cholinesterase (ChE) level and adverse clinical outcomes, including hypoxemia severity, hypercapnia, duration of hospital stay (DoHS), and noninvasive ventilation (NIV) requirement, in patients with AECOPD. Methods: Patients hospitalized with AECOPD in the Wuhu Hospital of Traditional Chinese Medicine between January 2017 and December 2021 were included. Results: A total of 429 patients were enrolled. The serum ChE level was significantly lower in patients with hypercapnia, who required NIV during hospitalization and who had a DoHS of >10 days, with an oxygenation index < 300. The ChE level was correlated negatively with the C-reactive protein level and neutrophil-to-lymphocyte ratio and correlated positively with the serum albumin level. Multivariate logistic regression analysis indicated that a serum ChE level of ≤4116 U/L (OR = 2.857, 95% CI = 1.46-5.58, p = 0.002) was associated significantly with NIV requirement. Conclusions: The serum ChE level was correlated significantly with complicating severe hypoxemia, hypercapnia, prolonged DoHS, and the need for NIV in patients hospitalized with AECOPD. The serum ChE level is a clinically important risk-stratification biomarker in patients hospitalized with AECOPD.

A high concentration of fatty acids induces TNF-α as well as NO release mediated by the P2X4 receptor, and the protective effects of puerarin in RAW264.7 cells.

Circulating levels of free fatty acids (FFAs) are often found to be increased in patients with type 2 diabetes mellitus (T2DM) and metabolic syndrome (MS). High plasma FFA levels may give rise to maladaptive macrophage activation and promote inflammatory responses, which has been proposed as a potential mechanism for the development of DM and MS. P2X4 receptor (P2X4R), a ligand-gated cation channel activated by extracellular adenosine triphosphate (ATP), plays a primary role in the regulation of inflammatory responses. Puerarin has been reported to possess potential anti-inflammatory activity. However, the anti-inflammatory activity of puerarin and the underlying molecular mechanisms in a setting of a high concentration of FFAs remain unknown. In this study, we found that a high concentration of FFAs increased the expression of P2X4R, cytosolic Ca2+ concentration and the phosphorylation of extracellular signal-regulated kinase (ERK) and induced the expression of tumor necrosis factor (TNF)-α and inducible nitric oxide synthase (iNOS) mRNA and the release of TNF-α and nitric oxide (NO) in RAW264.7 macrophages. Such a high concentration FFA-induced inflammation may be reversed by the P2X4R selective antagonist 5-BDBD, which manifests the important role of P2X4R in the TNF-α and NO release caused by the high concentration of FFAs in RAW264.7 cells. Molecular docking data showed that puerarin could interfere with the activation of P2X4R by forming hydrogen bonding towards residue Arg267, an important residue essential for the canonical activation of P2X4R. Treatment with puerarin dose-dependently reduced high concentration FFA-elevated P2X4R expression and inhibited P2X4R-mediated inflammatory signalling, including high concentration FFA-evoked [Ca2+]i, ERK phosphorylation, expression of TNF-α and iNOS mRNA and release of TNF-α and NO. Our findings emphasize the critical role of P2X4R in high concentration FFA-induced TNF-α and NO release of RAW264.7 macrophages. Puerarin notably counteracts these high concentration FFA-induced adverse effects through its inhibition of P2X4R expression and P2X4R-mediated inflammatory signalling.

[Cynomorium songaricum improves sperm count and motility and serum testosterone level and promotes proliferation of undifferentiated spermatogonia in oligoasthenospermia rats].

OBJECTIVE: To investigate the effects of cynomorium songaricum (CS) decoction on the testis weight, serum testosterone level, and sperm parameters of rats with oligoasthenospermia (OAS), explore its action mechanism of improving the proliferation of undifferentiated spermatogonial cells, and provide some experimental and theoretical evidence for the development of new Chinese drugs for OAS. METHODS: Thirty 8-week-old male SD rats were randomly divided into five groups of equal number: blank control, model control, high-dose CS, medium-dose CS, and low-dose CS. OAS models were established by intraperitoneal injection of cyclophosphamide and, a month later, treated intragastrically with normal saline or CS at 2, 1, and 0.5 g per kg of the body weight per day, all for 4 weeks. Then, the testes of the animals were harvested to obtain the testicular weight, sperm concentration and motility, and the level of serum testosterone (T), detect the expressions of the transcription factor 1 (Oct4), Thy-1 cell surface antigen (Thy1), promyelocytic leukemia zinc finger (PLZF), KIT proto-oncogene receptor tyrosine kinase (C-kit) and glial cell-derived neurotrophic factor (GDNF) in the testis tissue of the rats in the low-dose CS group by real-time PCR. RESULTS: The testis weights in the blank control, model control, high-dose CS, medium-dose CS, and low-dose CS groups were (1.52±0.06), (1.55±0.06), (1.43±0.30), (1.35±0.40) and (1.34±0.04) g, respectively, not significantly different in the blank and model controls from those in the CS groups (P>0.05). The visual field sperm count per 10 HP was significantly increased in the high-, medium-, and low-dose CS groups (202±20, 196±5 and 216±25) as compared with the blank and model controls (200±15 and 134±30) (P<0.05). The mRNA expressions of the Oct4, Thy1, PLZF and GDNF genes were remarkably higher in the low-dose CS group than in the controls (P<0.05), but that of the C-kit gene showed no significant difference from the latter (P>0.05). The visual field sperm motility per 10 HP was markedly increased in the blank control (ï¼»52.1±5.5ï¼½%), model control (ï¼»38.1±2.5ï¼½%), high-dose CS (ï¼»59.1±9.5ï¼½%), medium-dose CS (ï¼»58.7±9.5ï¼½%), and low-dose CS (ï¼»49.6±1.0ï¼½%) groups, and so was the level of serum testosterone (ï¼»190±87.5ï¼½, ï¼»82.5±25.8ï¼½, ï¼»229±75.6ï¼½, ï¼»331±86.7ï¼½ and ï¼»185±82.4ï¼½ mmol/L), both remarkably higher in the CS groups than in the model controls (P<0.05) but with no statistically significant difference between the CS groups and the blank controls (P>0.05). CONCLUSIONS: CS can significantly improve sperm concentration, sperm motility and serum T level in OAS rats, probably by inducing the expression of GDNF in the rat Sertoli cells, promoting the proliferation of undifferentiated spermatogonial cells, and enhancing spermatogenesis.

The Study of the Effect of Hedyotis diffusa on the Proliferation and the Apoptosis of the Cervical Tumor in Nude Mouse Model.

To study the inhibitory effect of Hedyotis diffusa on cervical cancer and its underlining biomolecular mechanism. Human cervical carcinoma nude mice xenograft was established and the mice were treated by intra-gastric administration of boiled and concentrated Hedyotis diffusa. When the tumor grew to 10 mm in diameter, the mice were randomly divided into Hedyotis diffusa Willd. (HDW) group and control group. The tumor inhibitory rate, survival time, and the expression rate of Ki-67 protein in Hela cells as well as tumor cell apoptosis were compared between these two groups. Hedyotis diffusa had inhibitory effect on cervical cancer cells and induced apoptosis of Hela cells. The expression of Ki-67 protein significantly decreased (P < 0.05) in HDW group, and the mean survival time of the mice was significantly extended (P < 0.05). Hedyotis diffusa directly inhibited the proliferation of cervical cancer cells and induced apoptosis of the tumor cells. It has a positive effect for the treatment of cervical cancer to achieve the goal of clearing the heat, removing the toxins, eliminating the stasis, and dissolving the masses.