Chinese medicinal formula Fu Xin decoction against chronic heart failure by inhibiting the NLRP3/caspase-1/GSDMD pyroptotic pathway.

BACKGROUND: Various heart diseases ultimately lead to chronic heart failure (CHF). In CHF, the inflammatory response is associated with pyroptosis, which is mediated by the NOD-like receptor protein 3 (NLRP3) inflammasome. Fu Xin decoction (FXD) is commonly used in clinical practice to treat CHF and improve inflammatory conditions. However, the specific pharmacological mechanisms of action for FXD in these processes have yet to be fully understood. PURPOSE: The objective of this study was to examine the protective mechanism of FXT against CHF, both in H9c2 cells and mice. METHOD: A CHF mouse model was established, and the effect of FXD was observed via gavage. Cardiac function was evaluated using echocardiography, while serum BNP and LDH levels were analyzed to assess the severity of CHF. Hematoxylin and eosin staining (H&E) and Masson staining were performed to evaluate myocardial pathological changes, and TdT-mediated dUTP Nick-End Labeling staining was used to detect DNA damage. Additionally, doxorubicin was utilized to induce myocardial cell injury in H9c2 cells, establishing a relevant model. CCK8 was used to observe cell viability and detect LDH levels in the cell supernatant. Subsequently, the expression of pyroptosis-related proteins was detected using immunohistochemistry, immunofluorescence, and western blotting. Finally, the pharmacological mechanism of FXD against CHF was further validated by treating H9c2 cells with an NLRP3 activator and inducing NLRP3 overexpression. RESULT: According to current research findings, echocardiography demonstrated a significant improvement of cardiac function by FXD, accompanied by reduced levels of BNP and LDH, indicating the amelioration of cardiac injury in CHF mice. FXD exhibited the ability to diminish serum CRP and MCP inflammatory markers in CHF mice. The results of HE and Masson staining analyses revealed a significant reduction in pathological damage of the heart tissue following FXD treatment. The CCK8 assay demonstrated the ability of FXD to enhance H9c2 cell viability, improve cell morphology, decrease LDH levels in the cell supernatant, and alleviate cell damage. Immunohistochemistry, Western blotting, and immunofluorescence staining substantiated the inhibitory effect of FXD on the NLRP3/caspase-1/GSDMD pyroptosis signaling pathway in both CHF and H9c2 cell injury models. Ultimately, the administration of the NLRP3 activator (Nigericin) and the overexpression of NLRP3 counteract the effects of FXD on cardiac protection and pyroptosis inhibition in vitro. CONCLUSION: FXD exhibits a cardioprotective effect, improving CHF and alleviating pyroptosis by inhibiting the NLRP3/caspase-1/GSDMD pathway.

Investigation and analysis of the working status and development situation of psychotherapy in psychiatric hospitals / 上海交通大学学报（医学版）

Objective·To understand the current situation of psychotherapy applied and relevant personnel's working in psychiatric hospitals, and provide advice to facilitate and promote the integrated service team building of domestic mental health institutions and the industry development of psychological treatment. Methods·Ninety-six psychiatric hospitals in China were selected and self-compiled questionnaire was used during the investigation. The actual feedback was collected from 52 hospitals in 25 provinces. Results·① According to the classification criteria of ICD-10 mental disorder, patients mainly suffered from schizophrenia, schizotypal disorder and delusional disorder, followed by affective disorder, in the psychiatric hospitals. ② There were 50 (96.2％) hospitals with psychological outpatient clinics, and 37 (71.2％) hospitals were equipped with mental wards. ③ The main types of patients who came to the psychology department in the psychiatric hospitals were emotional disorders, neurosis, stress-related and physical form disorders. ④ The composition of psychotherapists was 6 physicians, 2 clinical psychologists, and 1 nurse. ⑤ The top five psychotherapy techniques used by the psychiatric hospitals were cognitive therapy, supportive psychotherapy, behavioral therapy, group therapy, and family therapy. ⑥ 44.2％ of the practitioners working in this filed thought that the income had been too low if they only engaged in psychological treatment. Conclusion·In the staffing of mental health agency, compared to previous studies, the number of the psychology specialists increases, but it still makes up a small percentage, which does not match the needs of outpatient and ward patients. Psychological practitioners who rely on psychological treatment alone are in a lower income, and the gap between the expected income and actual income is too large. Government, health administration departments and hospitals should provide more support to psychological services and promote the development of institutions and personnel.

[Plasma concentration and pharmacokinetics of ursolic acid carried in self-microemulsifying drug delivery system in rats studied by UPLC-MS/MS].

This study is to report the establishment of an UPLC-MS/MS method for the determination of plasma concentration of UA carried in self-microemulsifying drug delivery system (SMEDDS) and its pharmacokinetics in rats. It was used for determination and analysis when serum with internal standard was extracted from C18 solid-phase column. Acquity UPLC BEH C18 column (100 mm x 2.1 mm, 1.7 microm) was used for separation. The mobile phase was acetonitrile -0.1% ammonia with gradient elution at the flow rate of 0.2 mL x min(-1). The column temperature was 40 degrees C and the detection wave length was 210 nm. It was detected by negative ion using electrospray ionization source (ESI) and scanned by multiple reaction ion monitoring (MRM) mode. The liner relationship of UA was very good in the range of 1.19-3 815.00 ng x mL(-1) (r = 0.999 0). Recovery rate of different concentrations were 87.42%-89.95%. The precision of inter-day and intra-day were less than 11%. The method developed in our study was proved to be sensitive, rapid and simple. It is suitable for the pharmacokinetic study of UA-SMEDDS in rats.

Herbal Extracts Combination (WNK) Prevents Decline in Spatial Learning and Memory in APP/PS1 Mice through Improvement of Hippocampal Aß Plaque Formation, Histopathology, and Ultrastructure.

To investigate the cognitive enhancement effect of WNK, an extracts combination of P. ginseng, G. biloba, and C. sativus L. and possible mechanisms, 5-month-old APP/PS1 transgenic mice were used in this study. After 3 months of administration, all mice received Morris water maze (MWM) training and a probe test. Mouse brain sections were detected by immunohistochemistry, HE staining, and transmission electron microscopy. MWM results showed significant difference between transgenic mice and nontransgenic littermates (P < 0.05, P < 0.01). WNK-treated mice exhibited enhanced maze performance over the training progression, especially better spatial memory retention in probe test compared to transgenic mice (P < 0.05, P < 0.01) and better spatial learning and memory at the fourth day of MWM test compared to EGB761- (G. biloba extract-) treated ones (P < 0.05). Hippocampal Aß plaque burden significantly differed between APP/PS1 and littermate mice (P < 0.001), while decreased Aß plaque appeared in WNK- or EGB761-treated transgenic brains (P < 0.05). Neurodegenerative changes were evident from light microscopic and ultrastructural observations in transgenic brains, which were improved by WNK or EGB761 treatment. These data indicate WNK can reduce the decline in spatial cognition, which might be due to its effects on reducing Aß plaque formation and ameliorating histopathology and ultrastructure in hippocampus of APP/PS1 mouse brain.

Effect of polydatin on action potential in ventricular papillary muscle of rat and the underlying ionic mechanism / 生理学报

It is proved that polydatin has cardioprotection against ischemia-induced arrhythmia, but the electrophysiological mechanism is not clear. The aim of the present study was to investigate the effect of polydatin on action potential (AP) in ventricular papillary muscle and the underlying ionic mechanism in rat using intracellular recording and whole-cell patch clamp techniques. The results showed: (1) In normal papillary muscles, polydatin (50 and 100 µmol/L) shortened duration of 50% repolarization (APD(50)) and duration of 90% repolarization (APD(90)) in a concentration-dependent manner (P<0.01). But polydatin had no effects on resting potential (RP), overshoot (OS), amplitude of action potential (APA) and maximal rate of depolarization in phase 0 (V(max)) in normal papillary muscles (P>0.05). (2) In partially depolarized papillary muscles, polydatin (50 µmol/L) not only shortened APD(50) and APD(90) (P<0.05), but also decreased OS, APA and V(max) (P<0.05). (3) After pretreatment with glibenclamide (10 µmol/L), an ATP-sensitive K(+) channel blocker, the electrophysiological effect of polydatin (50 µmol/L) was partially inhibited. (4) Pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME, 1 mmol/L), a nitric oxide (NO) synthase inhibitor, failed to abolish the effect of polydatin (50 µmol/L) on AP. (5) Polydatin (25, 50, 75 and 100 µmol/L) decreased L-type Ca(2+) current in ventricular myocytes in a concentration-dependent manner (P<0.05). (6) Polydatin (50 µmol/L) increased ATP-sensitive K(+) current in ventricular myocytes (P<0.05). The results suggest that polydatin can shorten the repolarization of AP in normal papillary muscle and inhibit AP in partially depolarized papillary muscle, which might be related to the blocking of L-type Ca(2+) channel and the opening of ATP-sensitive K(+) channel.