The medicinal materials of Bawei Chenxiang Pills(BCPs) were extracted via three methods: reflux extraction by water, reflux extraction by 70% ethanol, and extraction by pure water following reflux extraction by 70% ethanol, yielding three extracts of ST, CT, and CST. The efficacy of ST(760 mg·kg~(-1)), CT(620 mg·kg~(-1)), and CST(1 040 mg·kg~(-1)) were evaluated by acute myocardial ischemia(AMI) and p-chlorophenylalanine(PCPA)-induced insomnia in mice, respectively. Western blot was further utilized to investigate their hypnosis mechanisms. The main chemical components of different extracts were identified by the UPLC-Q-Exactive-MS technique. The results showed that CT and CST significantly increased the ejection fraction(EF) and fractional shortening(FS) of myocardial infarction mice, reduced left ventricular internal dimension at end-diastole(LVIDd) and left ventricular internal dimension at end-systole(LVIDs). In contrast, ST did not exhibit significant effects on these parameters. In the insomnia model, CT significantly reduced sleep latency and prolonged sleep duration, whereas ST only prolonged sleep duration without shortening sleep latency. CST showed no significant effects on either sleep latency or sleep duration. Additionally, both CT and ST upregulated glutamic acid decarboxylase 67(GAD67) protein expression in brain tissue. A total of 15 main chemical components were identified from CT, including 2-(2-phenylethyl) chromone and 6-methoxy-2-(2-phenylethyl) chromone. Six chemical components including chebulidic acid were identified from ST. The results suggested that chromones and terpenes were potential anti-myocardial ischemia drugs of BCPs, and tannin and phenolic acids were potential hypnosis drugs. This study enriches the pharmacological and chemical research of BCPs, providing a basis and reference for their secondary development, quality standard improvement, and clinical application.
Animals ; Drugs, Chinese Herbal/isolation & purification* ; Mice ; Male ; Sleep Initiation and Maintenance Disorders/physiopathology* ; Humans ; Myocardial Infarction/drug therapy* ; Myocardial Ischemia/drug therapy*

In addition to providing energy for cells, mitochondria also participate in calcium homeostasis, cell information transfer, cell apoptosis, cell growth and differentiation. Therefore, maintaining mitochondrial homeostasis is very crucial for the body to carry out normal life activities. Ubiquitination, a post-translational modification of proteins, is involved in various physiological and pathological processes of cells by regulating mitochondrial homeostasis. However, the mechanism by which ubiquitination regulates mitochondrial homeostasis has not been summarized, especially the effect of Parkin protein on cardiovascular diseases. In this paper, the specific mechanism of mitochondrial homeostasis regulated by ubiquitination of Parkin protein is discussed, and the influence of mitochondrial homeostasis imbalance on cardiovascular diseases is reviewed, with a view to providing potential therapeutic strategies for the clinical treatment of cardiovascular diseases.

Objective: The docking and superantigen activity sites of staphylococcal enterotoxin-like W (SElW) and T cell receptor (TCR) were predicted, and its SElW was cloned, expressed and purified. Methods: AlphaFold was used to predict the 3D structure of SElW protein monomers, and the protein models were evaluated with the help of the SAVES online server from ERRAT, Ramachandran plot, and Verify_3D. The ZDOCK server simulates the docking conformation of SElW and TCR, and the amino acid sequences of SElW and other serotype enterotoxins were aligned. The primers were designed to amplify selw, and the fragment was recombined into the pMD18-T vector and sequenced. Then recombinant plasmid pMD18-T was digested with BamHⅠand Hind Ⅲ. The target fragment was recombined into the expression plasmid pET-28a(+). After identification of the recombinant plasmid, the protein expression was induced by isopropyl-beta-D- thiogalactopyranoside. The SElW expressed in the supernatant was purified by affinity chromatography and quantified by the BCA method. Results: The predicted three-dimensional structure showed that the SElW protein was composed of two domains, the amino-terminal and the carboxy-terminal. The amino-terminal domain was composed of 3 α-helices and 6 β-sheets, and the carboxy-terminal domain included 2 α-helices and 7 antiparallel β-sheets composition. The overall quality factor score of the SElW protein model was 98.08, with 93.24% of the amino acids having a Verify_3D score ≥0.2 and no amino acids located in disallowed regions. The docking conformation with the highest score (1 521.328) was selected as the analysis object, and the 19 hydrogen bonds between the corresponding amino acid residues of SElW and TCR were analyzed by PyMOL. Combined with sequence alignment and the published data, this study predicted and found five important superantigen active sites, namely Y18, N19, W55, C88, and C98. The highly purified soluble recombinant protein SElW was obtained with cloning, expression, and protein purification. Conclusions: The study found five superantigen active sites in SElW protein that need special attention and successfully constructed and expressed the SElW protein, which laid the foundation for further exploration of the immune recognition mechanism of SElW.
Humans ; Enterotoxins/genetics* ; Superantigens/genetics* ; Catalytic Domain ; Selenoprotein W/metabolism* ; Receptors, Antigen, T-Cell

Objective: To investigate the clinical features and long-term prognosis of primary biliary cholangitis (PBC) in patients with past hepatitis B virus (HBV) infection. Methods: 353 cases with PBC who visited the Liver Disease Center of Beijing Friendship Hospital Affiliated to Capital Medical University between January 2000 and January 2018 were retrospectively analyzed and were divided into the past HBV infection group (156 cases) and the no HBV infection group (197 cases). The two groups' baseline clinical features were compared. Ursodeoxycholic acid response rate after one year, GLOBE score, UK-PBC score, and long-term liver transplantation-free survival rate were compared through outpatient and telephone follow-up. Results: PBC with past HBV infection had a significantly reduced female proportion compared to the no HBV infection group (91.9% vs. 79.5%, P = 0.001). However, there were no statistically significant differences in age, biochemical indices, immunological indicators, platelet count, cirrhosis proportion, and others. Ursodeoxycholic acid biochemical response rate was reduced in patients with past HBV infection at the end of one year of treatment, but the difference was not statistically significant (65.8% vs. 78.2%, P = 0.068). In addition, there were no statistically significant differences between the GLOBE score (0.57 vs. 0.59, P = 0.26) and UK-PBC 5-year (2.87% vs. 2.87%, P = 0.38), 10-year (9.29% vs. 8.2%, P = 0.39) and 15-year liver transplantation rates (16.6% vs. 14.73%, P = 0.39). Lastly, the overall 5-year liver transplantation-free survival rate had no statistically significant difference between the two groups of patients (86.4% vs. 87.5%, P = 0.796). Conclusion: Primary biliary cholangitis had no discernible effect in terms of age at onset, biochemical indices, immunological indicators, cirrhosis proportion, ursodeoxycholic acid response rate after one year, GLOBE score, UK-PBC score, or overall liver transplantation-free survival rate in patients with past hepatitis B virus infections.

In this study, the content of five heavy metals(Pb, Cd, As, Hg, and Cu) in 59 batches of Lonicerae Japonicae Flos(LJF) medicinal materials and pieces were determined by inductively coupled plasma mass spectrometry(ICP-MS). The health risk assessment was processed using the maximum estimated daily intake(EDI), target hazard quotients(THQ), and carcinogenic risks(CR) assessment models. With reference to the limit standard for heavy metal content in LJF specified in 2020 edition of Chinese Pharmacopoeia, five batches produced in Hebei were found to contain excessive Pb, and the remaining 54 batches met the specifications, with the unqualified rate of 8.47%. Comparative analysis of heavy metal content in LJF samples from three different producing areas, namely Shandong, Henan, and Hebei showed that the levels of Pb, As, and Hg in LJF from Hebei were significantly higher than those from Henan and Shandong. The samples produced in Shandong contained the highest content of Cd. The samples from Hebei contained the highest content of Cu while those from Shandong had the lowest content of Cu. As demonstrated by health risk assessment based on the EDI, THQ and CR models, these 59 batches of LJF samples did not cause significant health hazards for the exposed population, and there was no potential non-carcinogenic or carcinogenic risk. In conclusion, a few of LJF samples contained excessive heavy metals, so some measures, including controlling production environment, cultivating management mode, and optimizing processing methods, should be taken for ensuring the medication safety of LJF.
Drugs, Chinese Herbal ; Environmental Pollution/analysis* ; Mercury/toxicity* ; Metals, Heavy/toxicity* ; Risk Assessment

Objective: To compare and correlate the findings of intravoxel incoherent motion (IVIM) magnetic resonance (MR) imaging and arterial spin labeling (ASL) imaging in characterizing parotid gland tumors. Materials and Methods: We retrospectively reviewed 56 patients with parotid gland tumors evaluated by MR imaging. The true diffusion coefficient (D), pseudo-diffusion coefficient (D*), and fraction of perfusion (f) values of IVIM imaging and tumor-to-parotid gland signal intensity ratio (SIR) on ASL imaging were calculated. Spearman rank correlation coefficient, chi-squared, Mann-Whitney U, and Kruskal-Wallis tests with the post-hoc Dunn-Bonferroni method and receiver operating characteristic curve assessments were used for statistical analysis. Results: Malignant parotid gland tumors showed significantly lower D than benign tumors (p = 0.019). Within subgroup analyses, pleomorphic adenomas (PAs) showed significantly higher D than malignant tumors (MTs) and Warthin’s tumors (WTs) (p < 0.001). The D* of WTs was significantly higher than that of PAs (p = 0.031). The f and SIR on ASL imaging of WTs were significantly higher than those of MTs and PAs (p < 0.05). Significantly positive correlation was found between SIR on ASL imaging and f (r = 0.446, p = 0.001). In comparison with f, SIR on ASL imaging showed a higher area under curve (0.853 vs. 0.891) in discriminating MTs from WTs, although the difference was not significant (p = 0.720). Conclusion IVIM and ASL imaging could help differentiate parotid gland tumors. SIR on ASL imaging showed a significantly positive correlation with f. ASL imaging might hold potential to improve the ability to discriminate MTs from WTs.

Objective:To observe the effects of acupuncture on the characteristics of neuro-electrophysiological activity in hippocampal CA1 and CA3 areas of rats with post-traumatic stress disorder (PTSD).Methods:Fifty Sprague-Dawley (SD) rats were randomly divided into a blank group,a model group,a grasping group,a Western medicine group and an acupuncture group,with 10 rats in each group.Except for the blank group,rats in the other 4 groups all received the combined stress modeling method.Rats in the Western medicine group were intragastrically administrated with paroxetine hydrochloride,those in the acupuncture group received acupuncture intervention,those in the grasping group received grasping fixation,and those in the model group and the blank group did not receive any interventions.After 14 d of intervention,the interspike interval (ISI) and power spectral densities (PSD) were analyzed and mapped by in vivo multiple channels to record the neuron clusters discharge in the hippocampal CA1 and CA3 areas.Results:Compared with the blank group,ISI was prolonged in the CA1 and CA3 areas of the model group and the grasping group,and the concentrated PSD distribution area moved down (P＜0.05 or P＜0.01).Compared with the grasping group,the ISI of the CA1 and CA3 areas in the Western medicine group and the acupuncture group was shortened,and the concentrated PSD distribution area moved up (P＜0.05 or P＜0.01).The ISI and PSD distributions in the CA1 and CA3 areas of the acupuncture group were not statistically different from those in the Western medicine group (both P＞0.05).Conclusion:Both acupuncture and paroxetine hydrochloride can significantly regulate the neuro-electrophysiology activity of hippocampal CA1 and CA3 areas in PTSD rats,which may be one of the mechanisms of acupuncture intervention to promote PTSD recovery.

OBJECTIVE: Epstein-Barr virus associated gastric cancer (EBVaGC) is different from the traditional gastric cancer (Epstein-Barr virus non-associated gastric cancer, EBVnGC), and has unique clinicopathological features. This study investigated the largest single center cancer series so as to establish the clinicopathological and molecular characteristics of EBVaGC in China. METHODS: A retrospective analysis was conducted on EBVaGC and EBVnGC patients diagnosed at Peking University Cancer Hospital from 2003 to 2018 by comparing their clinicopathological features and prognosis. The gastric cancer (GC) dataset of public database was analyzed to obtain differentially expressed genes. The expression of important genes and their association with prognosis of GC were verified in GC tissues from our hospital. RESULTS: In this study, 3 241 GC patients were included, and a total of 163 EBVaGC (5.0%) patients were identified. Compared with EBVnGC, EBVaGC was higher in male and younger patients, and positively associated with remnant GC, poorly differentiated adenocarcinoma, and mixed type GC. EBVaGC was inversely related to lymph node metastasis. The 5-year survival rate of EBVnGC and EBVaGC was 59.6% and 63.2% respectively (P<0.05). In order to explore molecular features of EBVaGC, the Cancer Genome Atlas (TCGA) dataset was analyzed (n=240), and 7 404 significant differentially expressed genes were obtained, involving cell proliferation, apoptosis, invasion and metastasis. The down-regulated invasion/metastasis gene SALL4 and the up-regulated immune checkpoint gene PD-L1 were important molecular features of EBVaGC. Validation of these two genes in large GC series showed that the majority of the EBVaGC was SALL4 negative (1/92, 1.1%, lower than EBVnGC, 303/1 727, 17.5%), and that PD-L1 was mostly positive in EBVaGC (81/110, 73.6%, higher than EBVnGC, 649/2 350, 27.6%). GC patients with SALL4 negative and PD-L1 positive were often associated with better prognosis. CONCLUSION EBVaGC is a unique subtype of GC with less metastasis and a good prognosis. It also has a distinct molecular background. The down-regulation of invasion/metastasis gene SALL4 and up-regulation of immune checkpoint gene PD-L1 are important molecular features.
China ; Epstein-Barr Virus Infections/complications* ; Female ; Herpesvirus 4, Human ; Humans ; Male ; Retrospective Studies ; Stomach Neoplasms/etiology*

OBJECTIVETo explore the effect of Biejiajian Oral Liquid (, BOL) on CCl-induced hepatic fibrosis in rats by detecting the changes in the levels of angiotensin II (Ang II), angiotensin-(1-7) [Ang-(1-7)], angiotensin-converting enzyme (ACE), ACE2, angiotensin II type 1 receptor (AT1R), Mas, etc. METHODS: A total of 180 Wistar rats were randomly divided into two groups by random digital table method: prevention experiment and treatment experiment. Each group was further subdivided into the following 6 subgroups: normal control group, model group, vitamin E [100 mg/(kg·d), VE] group, enalapril [10 mg/(kg·g), Ena] group, high-dosage [20 g/(kg·d)] BOL group, and low-dosage [10 g/(kg·d)] BOL group. The hepatic fibrosis rat model was established by subcutaneous injection of CCl for 6 weeks. Prevention experiment and treatment experiment were administered with specific drugs at different times. At the end of treatment experiment, the pathological changes of liver were observed after hematoxylin-eosin staining. The expressions of ingredients in renin-angiotensin-aldosterone system (RAAS) such as AngII, Ang-(1-7), ACE, ACE2, AT1R, Mas, renin, CYP11B2 and angen in liver were detected by enzyme linked immunosorbent assay, immunohistochemistry method or reverse transcription-polymerase chain reaction, respectively.

RESULTSThe levels of AngII and Ang-(1-7) at the 6th week increased by 496.10% and 73.64%, respectively, compared with those at the 2nd week in the model group (P<0.01). With prevention or treatment with high-dosage BOL, there was an evident reduction of AngII level but an improvement of Ang-(1-7) level. Specifically, AngII level of high-dosage group decreased by 77.50% in prevention experiment (P=0.000) and by 76.93% in treatment experiment (P=0.002) compared with that in the model group. Ang-(1-7) level increased by 91.69% in prevention experiment (P=0.006) and by 70.77% in the treatment experiment (P=0.010) compared with that in the model group. The expression levels of mRNA of renin, ACE, CYP11B2, angen and AT1R decreased by 58.15%, 99.90%, 99.84%, 99.99% and 99.99% (all P<0.01), respectively.

CONCLUSIONSBOL could help resist liver fibrosis in rats by enhancing the level of each ingredient in ACE2-Ang-(1-7)-Mas axis, while decreasing the level of each ingredient in ACE-AngII-AT1R axis. To some extent, BOL could enhance the regulation of RAAS in rats with CCl-induced hepatic fibrosis.

OBJECTIVETo analyze serum levels of non-esterified fatty acids (NEFA) and albumin (ALB) in children with nephrotic syndrome (NS) and investigate the clinical significance of altered serum NEFA to ALB ratio in children with NS in acute and remission phases.

METHODSSerum levels of NEFA and ALB were measured in 55 NS children in acute phase, in 33 NS children in remission and in 122 healthy control children, and the ratio of NEFA to ALB was calculated. The other lipid/lipoprotein and renal function parameters were also analyzed in these children.

RESULTSCompared with the healthy control children, children with NS had a significantly decreased serum ALB level (t=11.152, P<0.001) and a significantly increased NEFA to ALB ratio (t=4.991, P<0.001). Compared with NS children in remission, those in acute phase showed a significantly decreased ALB (Z=7.822, P<0.001) and an increased NEFA to ALB ratio (t=4.991, P<0.001). In all the NS children, NEFA to ALB ratio was positively correlated with the levels of TC (r=0.564, P<0.001), TG (r=0.444, P<0.001), LDL-C (r=0.625, P<0.001), urea (r=0.437, P<0.001), creatinine (r=0.278, P=0.013), and uric acid (r=0.397, P<0.001), while negatively correlated with the level of total protein (r=-0.461, P<0.001). Multiple linear regression analyses showed that NEFA to ALB ratio was independently associated with serum urea levels (β=0.703, P=0.001; adjusted R=0.494) after adjustment of other related factors.

CONCLUSIONSerum NEFA to ALB ratio is significantly increased in NS children in close association with impaired kidney function, and may function as a novel parameter for assessing the development of NS.

Case-Control Studies ; Child ; Fatty Acids, Nonesterified ; blood ; Humans ; Nephrotic Syndrome ; blood ; Regression Analysis ; Serum Albumin, Human ; analysis