OBJECTIVES: To explore the bioactive components in Jiawei Xiaoyao Pills (JWXYP) and their mechanisms for alleviating depression-like behaviors. METHODS: The active compounds, key targets, and pathways of JWXYP were identified using TCMSP and TCMIP databases. Thirty-six SD rats were randomized equally into 6 groups including a control group and 5 chronic unpredictable mild stress (CUMS)-induced depression groups. After modeling, the 5 model groups were treated with daily gavage of normal saline, 1.8 mg/kg fluoxetine hydrochloride (positive control drug), or JWXYP at 1.44, 2.88, and 4.32 g/kg. The depression-like behaviors of the rats were evaluated using behavioral tests, and pathological changes in the liver and hippocampus were examined with HE staining. The biochemical indicators in the serum and brain tissues were detected using ELISA. Serum metabolomics analysis was performed to identify the differential metabolites using OPLS-DA, and gut microbiota changes were analyzed using 16S rDNA sequencing. RESULTS: Network pharmacology revealed that menthone and paeonol in JWXYP were capable of penetrating the blood-brain barrier to regulate inflammatory pathways and protect the nervous system. In the rat models subjected to CUMS, treatment with JWXYP significantly improved body weight loss, sucrose preference and open field activities, reduced liver inflammation, alleviated structural changes in the hippocampal neurons, decreased serum levels of TNF‑α, IL-1β, IL-6 and LBP, and increased 5-HT and VIP concentrations in the serum and brain tissue, and these effects were the most pronounced in the high-dose group. Metabolomics analysis showed changes in such metabolites as indole-3-acetamide and acetyl-L-carnitine in JWXYP-treated rats, involving the pathways for bile acid biosynthesis and amino acid metabolism. 16S rDNA analysis demonstrated increased gut microbiota diversity and increased abundance of Lactobacillus species in JWXYP-treated rats. CONCLUSIONS JWXYP alleviates depression-like symptoms in rats by regulating the neurotransmitters, inhibiting inflammation and oxidation, and modulating gut microbiota.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Gastrointestinal Microbiome/drug effects* ; Rats, Sprague-Dawley ; Depression/drug therapy* ; Neurotransmitter Agents/metabolism* ; Rats ; Inflammation ; Male ; Hippocampus ; Behavior, Animal/drug effects*

Objective To analyze the effects of intensive treatment with insulin pump and insulin aspart+insulin glargine 3+1.Methods Fifty patients with type 2 diabetes mellitus(T2DM)in our hospital were randomly divided into insulin aspart+insulin glargine(Asp+Gla)group and insulin pump(IP)group,with 25 cases in each group.Compare the general data,biochemical indicators,serum malondialdehyde(MDA),catalase(CAT),superoxide dismutase(SOD)and adverse reactions between the two groups,and calculate the insulin resistance index(HOMA-IR)and islet β function index(HOMA-β).Results HOMA-β,HDL-C,SOD and CAT in the two groups were higher than those before treatment(P<0.05),while FPG,2 hPG,GA,HOMA-IR,TG,TC,LDL-C and MDA were lower than those before treatment(P<0.05).Compared with Asp+Gla group after treatment,HDL-C,SOD and CAT in IP group increased(P<0.05),while FPG,2 hPG,GA,HOMA-β,HOMA-IR,TG,TC,LDL-C and MDA decreased(P<0.05).Conclusions Intensive treatment with insulin pump can more effectively regulate the level of glucose and lipid metabolism,improve insulin β function and reduce oxidative stress,which is safe and effective.

Objective:To investigate the clinical and imaging features of spontaneous convexal subarachnoid hemorrhage (cSAH) with acute cerebral infarction.Methods:Nine patients with cSAH complicated with acute cerebral infarction, admitted to our hospital from January 2018 to October 2021, were selected. The clinical data and efficacy of these patients were retrospectively analyzed.Results:The time from cSAH to the onset of acute cerebral infarction was 5-144 h, with median time of 2 d. The most common bleeding site of cSAH was the parietal lobe ( n=6); cSAH in the ipsilateral side of acute cerebral infarction was noted in 4 patients. Six patients had middle cerebral artery stenosis or occlusion, and 2 patients had anterior cerebral artery stenosis or occlusion. Hypertension ( n=7) was the most common primary disease; 7 patients were treated with antiplatelet drugs, anticoagulants and/or stents. The follow-up at 3 months after cSAH showed that 6 patients had good prognosis and one had poor prognosis. Conclusions:The cSAH often occurs 2 d after acute cerebral infarction; intracranial artery stenosis or occlusion may be the main cause of the disease. In patients complicated with cSAH, active antiplatelet, anticoagulation and/or stent therapy do not increase the risk of bleeding, and the prognosis is good.

Objective: To study the protective effect of Ascorbic acid (AA) on the injury of nickel-exposed mouse embryonic fibroblasts (NIH/3T3) . Methods: A model of damage induced by 50 μg/mL nickel refining dust was established to determine the relative survival rate of cells, superoxide dismutase (SOD) , lactate dehydrogenase (LDH) and glutathione peroxidase. (GSH-Px) activity, hydrogen peroxide (H₂O₂) and malondialdehyde (MDA) content, and p53 (wild-type) , Bcl-2 protein expression. To investigate the protective effect of different doses of ascorbic acid (25, 50, 100 mmol/L) on nickel-refined dust-induced NIH/3T3 cell injury. Results: The study showed that ascorbic acid Ⅲ group can make the NIH/3T3 cell survival rate increased significantly; Apoptosis rate was reduced; The vitality of SOD and GSH-Px increased significantly, and the difference was statistically significant (P<0.05) . At the same time, the level of MDA and H₂O₂ and the activity of extracellular LDH enzyme were significantly reduced, and the difference was statistically significant (P<0.05) . The results showed that nickel refining dust induced cell damage through up-regulation of p53 protein and down-regulation of Bcl-2 protein expression; ascorbic acid interventions, the expression level of Bcl-2 protein in ascorbic acid II and III groups was higher than that of nickel refining dust group, and the difference was statistically significant (P<0.05); The expression level of p53 protein in each dose group of ascorbic acid was lower than that of nickel refined dust group, and the difference was statistically significant (P<0.05). Conclusion With the increase of concentration of ascorbic acid, oxidative damage levels, antioxidant enzyme levels, reduce cell apoptosis, reduce expression of p53, increased expression of Bcl-2. It showed that ascorbic acid had protective effect on NIH/3T3 cell injury induced by nickel refining dust.

Objective To explore the effect of proximal femoral nail antirotation (PFNA) on treatment of elderly patients with intertrochanteric fractures.Methods A total of 90 elderly patients with intertrochanteric fractures were selected as observation group,and they were treated with PFNA.A total of 70 elderly patients with intertrochanteric fractures by treatment of dynamic hip screw were selected as control group.Surgical effect was compared between two groups.Results Compared with the control group,operation time,hospitalization time,full weight-bearing time and blood loss in the observation group were significantly better (P ＜ 0.05).There were no significant differences in excellent rate and postoperative complications between two groups (P ＞ 0.05).Conclusion PFNA has advantages such as short operation time and less blood loss in the treatment of elderly patients with intertrochanteric fractures.

Objective To explore the effect of proximal femoral nail antirotation (PFNA) on treatment of elderly patients with intertrochanteric fractures.Methods A total of 90 elderly patients with intertrochanteric fractures were selected as observation group,and they were treated with PFNA.A total of 70 elderly patients with intertrochanteric fractures by treatment of dynamic hip screw were selected as control group.Surgical effect was compared between two groups.Results Compared with the control group,operation time,hospitalization time,full weight-bearing time and blood loss in the observation group were significantly better (P ＜ 0.05).There were no significant differences in excellent rate and postoperative complications between two groups (P ＞ 0.05).Conclusion PFNA has advantages such as short operation time and less blood loss in the treatment of elderly patients with intertrochanteric fractures.

BACKGROUNDBased on the excellent medical care and management system for Chinese veterans, as well as the detailed medical documentation available, we aim to construct a Chinese Veteran Clinical Research (CVCR) platform on non-communicable diseases (NCDs) and carry out studies of the primary disabling NCDs.

METHODSThe Geriatric Neurology Department of Chinese People's Liberation Army General Hospital and veterans' hospitals serve as the leading and participating units in the platform construction. The fundamental constituents of the platform are veteran communities. Stratified typical cluster sampling is adopted to recruit veteran communities. A cross-sectional study of mental, neurological, and substance use (MNS) disorders are performed in two stages using screening scale such as the Mini-Mental State Examination and Montreal cognitive assessment, followed by systematic neuropsychological assessments to make clinical diagnoses, evaluated disease awareness and care situation.

RESULTSA total of 9 676 among 277 veteran communities from 18 cities are recruited into this platform, yielding a response rate of 83.86%. 8 812 subjects complete the MNS subproject screening and total response rate is 91.70%. The average participant age is (82.01±4.61) years, 69.47% of veterans are 80 years or older. Most participants are male (94.01%), 83.36% of subjects have at least a junior high school degree. The overall health status of veterans is good and stable. The most common NCD are cardiovascular disorders (86.44%), urinary and genital diseases (73.14%), eye and ear problems (66.25%), endocrine (56.56%) and neuro-psychiatric disturbances (50.78%).

CONCLUSIONWe first construct a veterans' comprehensive clinical research platform for the study of NCDs that is primarily composed of highly educated Chinese males of advanced age and utilize this platform to complete a cross-sectional national investigation of MNS disorders among veterans. The good and stable health condition of the veterans could facilitate the long-term follow-up studies of NCDs and provide prospective data to the prevention and management of NCDs.

Aged ; Aged, 80 and over ; Asian Continental Ancestry Group ; Cross-Sectional Studies ; Disease ; Female ; Health Status ; Humans ; Male ; Veterans ; statistics & numerical data

Objective To assess the expression pattern of protease-activated receptor 2 (PAR2) in human keratinocytes and to characterize its biological functions in the regulation of skin barrier.Methods Primary human keratinocytes and human N/TERT keratinocytes were used as the subject of this study.The expression and distribution of PAR2 in the keratinocytes were analyzed by using immunoflorescence staining and Western blot.Two different PAR2 agonists,trypsin and a PAR2-activating peptide (AP),as well as a PAR2-antagonistic peptide (H2N-FSLLRY-COOH) and a control peptide were used to induce the activation of PAR2 in the keratinocytes.Then,a fluorescence-based calcium mobilization assay was performed to evaluate the biological function of PAR2.Data were statistically analyzed by one-factor analysis of variance.Results Under normal culture conditions,PAR2 was weakly expressed in keratinocytes,and the expression was unaffected by culture medium composition or culture duration.Calcium mobilization was induced by trypsin of 50-250 nmol/L and the PAR2-activating peptide in a dose-and time-dependent pattern.The maximal activation of PAR2 was observed in keratinocytes treated with the PAR2 agonist HAN-SLIGKV-COOH of 75-250 μmol/L.The PAR2-antagonistic peptide (H2N-FSLLRY-COOH) obviously suppressed the increase in calcium mobilization induced by trypsin,while the control peptide PAR-RAP showed no inductive effect on the PAR2 activation based on the absence of calcium mobilization.The substrate-induced calcium release was complete within 250 seconds,and peaked at 50 seconds after the initial trypsin or PAR-AP stimulation.Moreover,the activation of PAR2 was accompanied by an increase in ERK phosphorylation and elicitation of MAPK signaling pathway in keratinocytes.Conclusions Human keratinocytes positively express PAR2,which can be activated by trypsin and PAR2-activating peptides,and the activation of PAR2 may influence the physiological function of keratinocytes by inducing intracellular calcium release.

Objective To investigate the cognition and behaviors of sun-protection and the facial photoaging in a Nanjing population, and to analyze the relationships between them. Methods The objects being investigated in Nanjing (n=974) were divided into 10 groups according to age. The ordinary information, knowledge and behavior of sun-protection and Glogau photoageing type of face were studied by questionnaires. The results were analyzed by a logistic regression model to select the related factors to photoageing. Results The risk of skin photoageing increased with age. Most of the 46-65 years old crowds were type Ⅲ photoageing. Most of the objects being investigated had some knowledge and active awareness of sun-protection and could use some ways to protect themselves from sun. However, most people did not use the sunscreen correctly. Those who had higher level awareness and knowledge of sunprotection suffered less risk from skin photoageing. Sunbath without sunscreen for a long time outside activity was a high risk factor of development to skin photoageing. Shade, broad-brimmed hat and sun-protection in autumn were the protective factors. Conclusion Active awareness and correct methods could help prevent skin photoageing. In order to avoid the damages to skin from ultraviolet efficiently, the accurate ways of using sunscreens should be well understood.

Objective To explore the influences of extracellular matrices (ECM) secreted by ultraviolet B (UVB)-induced senescent fibroblasts on the proliferation of and extracellular signal-regulated kinase (ERK) signaling in HaCaT cells. Methods Fibroblasts were irradiated with UVB of 15 mJ/cm2 once daily for 5 days to induce premature senescence, which was identified by SA-β-gal staining 72 hours after the last irradiation.HaCaT cells were divided into 3 groups and inoculated into plates coated with extracellular matrices secreted by non-senescent (PRE-ECM) or senescent fibroblasts (SIPS-ECM) or into uncoated plates (NON-ECM), fol-lowed by additional culture. U0126, an inhibitor of ERK1/2, was used to treat the HaCaT cells 1 hour before inoculation. Then, MTT assay was carried out to detect the proliferation of HaCaT cells after a 3-day culture,Western blot to assess the phosphorylation of ERK at 0.5, 1, 2 and 4 hours after the inoculation, flow cytometry to analyse cell cycle and apoptosis after 24 hours of culture. Results The most rapid and intense phosphory-lation of ERK was observed in SIPS-ECM group. Inhibiting the activation of ERK pathway with U0126 could completely suppress the promoting effect of ECM from senescent fibroblasts on the proliferation of HaCaT cells.After the blocking of ERK activation, the proportion of HaCaT cells in S and G2/M phase decreased from 37.40%, 41.34% and 43.31% to 29.41%, 36.48% and 39.96%, respectively, in NON-ECM, PRE-ECM and SCIP-ECM group. Conclusion The ECM produced by UVB-induced senescent fibroblasts promote the prolifera-tion of HaCaT cells via inducing the phosphorylation of ERK.