Protective Effect of Compound Tongluo Decoction on Brain Vascular Endothelial Cells after Ischemia-Reperfusion by Inhibition of Ferroptosis Through Regulating Nrf2/ARE/SLC7A11 Signaling Pathway.

Cerebral infarction is one of the most common diseases for aged people. Compound Tongluo Decoction (CTLD), a classic traditional Chinese Medicine prescription, has been widely used in the treatment of ischemic cerebral infarction. Transient middle cerebral artery occlusion (tMCAO) rat model is established for the animal experiment and oxygen-glucose deprivation and reperfusion (OGD/R) human umbilical vein endothelial cells (HUVECs) model are established for the cell experiment. This also use Nrf2-/- rats to detect the role of nuclear factor erythroid 2-related factor 2 (Nrf2). Longa score, Evans blue staining, brain water content measurement, and histological observation are done. The levels of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), and other ferroptosis-related components are detected respectively. In the vivo experiment, CTLD relieved ischemia-reperfusion (IR) injury symptoms and attenuated IR injury in brain tissues of tMCAO rats by relieving peroxidation injury in brain tissues and inhibiting ferroptosis in tMCAO rats. Moreover, CTLD reversed OGD/R-induced oxidative damage of endothelial cells via suppressing ferroptosis. After knocking out the Nrf2 gene, the protective effect of CTLD is sharply reduced. This study put forward that CTLD can inhibit ferroptosis in I/R-injured vascular endothelium by regulating Nrf2/ARE/SLC7A11 signaling to improve the relative symptoms of rats after cerebral I/R injury, thus providing a viable treatment option for cerebrovascular disease.

Treatment Outcomes in COVID-19 Patients with Brucellosis: Case Series in Heilongjiang and Systematic Review of Literature.

Objective: Clinical characteristics and outcome in COVID-19 with brucellosis patients has not been well demonstrated, we tried to analyze clinical outcome in local and literature COVID-19 cases with brucellosis before and after recovery. Methods: We retrospectively collected hospitalization data of comorbid patients and prospectively followed up after discharge in Heilongjiang Infectious Disease Hospital from January 15, 2020 to April 29, 2022. Demographics, epidemiological, clinical symptoms, radiological and laboratory data, treatment medicines and outcomes, and follow up were analyzed, and findings of a systematic review were demonstrated. Results: A total of four COVID-19 with brucellosis patients were included. One patient had active brucellosis before covid and 3 patients had nonactive brucellosis before brucellosis. The median age was 54.5 years, and all were males (100.0%). Two cases (50.0%) were moderate, and one was mild and asymptomatic, respectively. Three cases (75.0%) had at least one comorbidity (brucellosis excluded). All 4 patients were found in COVID-19 nucleic acid screening. Case C and D had only headache and fever on admission, respectively. Four cases were treated with Traditional Chinese medicine, western medicines for three cases, no adverse reaction occurred during hospitalization. All patients were cured and discharged. Moreover, one case (25.0%) had still active brucellosis without re-positive COVID-19, and other three cases (75.0%) have no symptoms of discomfort except one case fell fatigue and anxious during the follow-up period after recovery. Conducting the literature review, two similar cases have been reported in two case reports, and were both recovered, whereas, no data of follow up after recovery. Conclusion: These cases indicate that COVID-19 patients with brucellosis had favorable outcome before and after recovery. More clinical studies should be conducted to confirm our findings.

[Research and application of model fruit fly in prevention and treatment of neuropsychiatric disorders by traditional Chinese medicine and natural compounds: a review].

As an important model animal, fruit fly is characterized by outstanding genetic characteristics, relatively perfect nervous system, rapid reproduction, and low cost. Thus, it has been applied in the research on neuropsychiatric disorders in recent years, showing great potential in life science. The incidence of neuropsychiatric disorders has been on the rise, and the disorders have high disability rate and low case fatality rate. The global drug demand for such diseases is second only to cardiovascular and cerebrovascular diseases. At the moment, the demand of the drugs for the diseases have been rising, and it is an urgent task to develop related drugs. However, the research and development of the drugs are time-intensive and have a high failure rate. A suitable animal model can help shorten the time for drug screening and development, thereby reducing the cost and failure rate. This study reviews the application of fruit flies in several common neuropsychiatric disorders, which is expected to provide new ideas for the research and application of the model animals in traditional Chinese medicine.

New compounds from the stems of Fissistigma acuminatissimum Merr. and their in vitro anti-inflammatory activity.

Three new compounds, 4,5,6,7-tetramethoxy-3-benzoylbenzofuran (1), 4-hydroxy-3,5,6-trimethoxydihydrochalcone-2-O-ß-D-glucopyranoside (2) and 2-hydroxy-3,4,5,6-tetramethoxyphenylethyl benzoate (3) along with five known flavonoids were isolated from the dichloromethane fraction of the stems of Fissistigma acuminatissimum Merr.'s ethanol extracts. The compounds were obtained by chromatographic methods and the structure elucidation was completed primarily on the basis of spectroscopic analyses, all of these compounds were isolated from F. acuminatissimum for the first time. All the fractions and compounds were evaluated for their anti-inflammatory activity against lipopolysaccharide (LPS)-stimulated tumor necrosis factor α (TNF-α) production in RAW264.7 cells in vitro. The dichloromethane fraction showed the most potent inhibition(38.2%) at 60 µg/mL, compound 1 (70.2%) and 3 (65.2%) showed significant inhibition at 10 µM.

Impact of Lycium barbarum polysaccharide on the expression of glucagon-like peptide 1 in vitro and in vivo.

Several studies showed the efficacy of Lycium barbarum polysaccharide (LBP) in diabetic animals and patients with type 2 diabetes mellitus (T2DM). However, the mechanism of LBP in alleviating T2DM based on glucagon-like peptide 1 (GLP1) has not been suitably elucidated. GLP1 is an important peptide that plays a role in blood glucose homeostasis. Inhibition of sodium/glucose cotransporter 1 (SGLT1) can result in a net increase in GLP1 release. We found that LBP could reduce SGLT1 expression. Thus, the effects of LBP on the first- and second-phase secretion of GLP1 were systematically assessed in vitro using STC1 cells and in vivo using diabetic KKAy mice. LBP could induce the first-phase secretion of GLP1 by stimulating calcium ion influx in vitro and by inhibiting alpha-glucosidase activity in vivo. Regulation of Gcg gene expression by modulating the Wnt/ß-catenin and cAMP/Epac pathways, as well as inhibition of alpha-glucosidase activity, was responsible for the second-phase secretion of GLP1. LBP could stimulate GLP1 secretion; however, dipeptidyl peptidase 4 (DPP4) activated by LBP might offset the second-phase secretion of GLP1. Thus, we suggest considering the simultaneous use of LBP and a DPP4 inhibitor to stimulate slow, continuous GLP1 secretion. Further studies are warranted for in-depth mechanistic information.

Research and application of model fruit fly in prevention and treatment of neuropsychiatric disorders by traditional Chinese medicine and natural compounds: a review / 中国中药杂志

As an important model animal, fruit fly is characterized by outstanding genetic characteristics, relatively perfect nervous system, rapid reproduction, and low cost. Thus, it has been applied in the research on neuropsychiatric disorders in recent years, showing great potential in life science. The incidence of neuropsychiatric disorders has been on the rise, and the disorders have high disability rate and low case fatality rate. The global drug demand for such diseases is second only to cardiovascular and cerebrovascular diseases. At the moment, the demand of the drugs for the diseases have been rising, and it is an urgent task to develop related drugs. However, the research and development of the drugs are time-intensive and have a high failure rate. A suitable animal model can help shorten the time for drug screening and development, thereby reducing the cost and failure rate. This study reviews the application of fruit flies in several common neuropsychiatric disorders, which is expected to provide new ideas for the research and application of the model animals in traditional Chinese medicine.

[Effects of different drying methods on ginsenosides based on UHPLC-Q-Exactive Orbitrap MS technique].

The present study quickly identified the ginsenosides in fresh Panax ginseng and specified the effects of different drying methods(50 ℃-drying, 80 ℃-drying, and-70 ℃ freeze-drying) on ginsenosides.Three P.ginseng products by different drying methods were prepared, and the UHPLC-Q-Exactive Orbitrap high-resolution liquid mass spectrometry(MS) technique was applied to perform gradient elution using water-acetonitrile as the mobile phase, and the data collected in the negative ion mode were analyzed using X Calibur 2.2.The results showed that 57 saponins were identified from fresh P.ginseng.As revealed by the comparison with the fresh P.ginseng, in terms of the loss of ginsenosides, the dried products were ranked as the dried product at 50 ℃, freeze-dried products at-70 ℃, and the dried product at 80 ℃ in the ascending order.This study elucidated the effects of different drying methods on the types and relative content of ginsenosides, which can provide references for the processing of P.ginseng in the producing areas.

Tongxie-Yaofang formula regulated macrophage polarization to ameliorate DSS-induced colitis via NF-κB/NLRP3 signaling pathway.

BACKGROUND: Macrophages infiltration and activation play multiple roles in maintaining intestinal homeostasis and participate in the occurrence and development of UC. Thus, the restoration of immune balance can be achieved by targeting macrophage polarization. Previous studies have reported that TXYF could effectively ameliorate DSS-induced colitis. However, the underlying mechanisms of TXYF for DSS-induced colitis are still ill-defined. METHODOLOGY: This study was designed to explore the therapeutic effect of TXYF and its regulation in macrophages polarization during DSS-induced mice. In C75BL/6 mice, dextran sulfate sodium (DSS) was used to induce colitis and concomitantly TXYF was taken orally to evaluate its curative effect. In vitro experiment was implemented on BMDMs by lipopolysaccharide, IFN- and ATP. RESULTS: Here, we found that TXYF ameliorated clinical features in DSS-induced mice, decreased macrophages M1 polarization but remarkably increased M2 polarization. Mechanically, TXYF treatment effectively inhibited the activities of nuclear transcription factor NF-κB, which further contributed to the decrease of the inflammasome genes of NLRP3, limiting the activation of NLRP3 inflammasome in vivo and in vitro. CONCLUSION: Our findings demonstrated administration of TXYF can interfere with macrophage infiltration and polarization to improve the symptoms of acute colitis, by repressing NF-κB/NLRP3 signaling pathway activation. This enriches the mechanism and provides new prospect for TXYF in the treatment of colitis.

Effectiveness of six-step complex decongestive therapy for treating upper limb lymphedema after breast cancer surgery.

BACKGROUND: Complex decongestive therapy (CDT) is currently recommended as the standard treatment for lymphedema. CDT is a four-step detumescence therapy that can effectively treat upper limb lymphedema after breast cancer surgery, and is considered non-invasive, painless and without side effects. AIM: To determine the effectiveness of a six-step CDT involving a foam granule bandage for the treatment of upper extremity lymphedema pressure after breast cancer surgical intervention. METHODS: The study included 100 patients with upper extremity lymphedema after breast cancer surgery. The surgical methods were mastectomy plus axillary lymph node dissection and breast preservation plus sentinel lymph node biopsy. The study population was further divided into the experimental group and control group with 50 cases in each group. The control group was given conventional CDT (four-step method), which included skin care, freehand lymphatic drainage, foam granule pressurized bandage, and functional exercise. In the experimental group, a six-step CDT method was applied that involved a foam particle bandage combined with air wave pressure therapy in addition to the four steps of conventional CDT. Patients in both groups were given one course of treatment daily (20 times), and the changes in body moisture and subjective symptoms were measured before and after treatment, preoperatively and 20 times after treatment. RESULTS: No statistically significant differences in 50-Hz bioelectrical impedance and extracellular moisture ratio were observed between the two groups before treatment, suggesting comparability of the baseline data. After treatment, the 50-Hz bioelectrical impedance of the experimental group was significantly higher than that in the control group, and the extracellular moisture ratio was significantly lower than that in the control group. A comparison of the differences between the two groups before and after treatment indicated that the treatment effect in the experimental group was better than that in the control group. After 20 treatments, according to subjective evaluations, the tightness and swelling of the limbs in the experimental group were significantly reduced as compared with those in the control group. CONCLUSION: The six-step CDT method can effectively reduce lymphedema, promote lymphatic circulation, and alleviate the subjective symptoms of patients, and thereby improve the quality of life and treatment compliance among patients.

Efficacy and safety of Chinese herbal medicine Qirui Weishu capsule in treating chronic non-atrophic gastritis: A multicentre, double-blind, randomized controlled clinical trial.

ETHNOPHARMACOLOGICAL RELEVANCE: QiruiWeishu capsule is an herbal preparation from a herbal formula prescribed by an experienced doctor at Guang'anmen Hospital of China Academy of Chinese Medical Sciences. It has been used clinically for more than 30 years. Abdominal pain, distension, and nausea are common symptoms of chronic non-atrophic gastritis with erosion dampness and heat stasis syndrome, and this herbal medicine has been used to treat them. AIM OF THE STUDY: To verify the clinical efficacy and safety of QiruiWeishu capsule in the treatment of chronic non-atrophic gastritis with damp-heat stasis syndrome. MATERIALS AND METHODS: This study was a multicenter randomized double-blind clinical trial with positive herbal drug SanjiuWeitai capsule as control and superiority test of main efficacy. A total of 477 subjects with chronic non-atrophic gastritis with erosion diagnosed by gastroscopy and pathological biopsy were randomly divided into QiruiWeishu capsule and SanjiuWeitai groups respectively in a ratio of 3:1. During the trial, subjects were required to complete medication for 28 days. The primary outcome was the disappearance rate of epigastric pain from baseline to 4weeks. At baseline, treatment at 1, 2, and 4 weeks, and follow-up at 8 and 16 weeks, the epigastric pain and traditional Chinese medicine (TCM) symptom scores were evaluated; gastroscopy, histopathology, and the helicobacter pylori test were evaluated at baseline and after 4 weeks of treatment. The safety assessment included blood routine, liver and kidney function, coagulation of laboratory tests, and electrocardiogram (ECG). RESULTS: Both groups of subjects had a high level of medication adherence (defined as treatment completion for over 80%) (346/357, 96.9% in Qirui Weishu group vs 118/120, 98.3% in Sanjiu Weitai group; p > 0.05). The QiruiWeishu capsule was significantly better than SanjiuWeitai capsule in disappearance rate of epigastric pain (64.2%, 229/357vs 46.7%, 56/120; p < 0.001)，especially subgroupsubjects with moderate epigastric pain (65.0%, 89/137 vs 30.4%, 14/46; p < 0.001), grade1 erythema (67.7%, 149/220 vs 51.9%, 42/81; p = 0.011) and grade 2 erythema (57.6%, 70/121 vs37.1%, 13/35; p = 0.050) of gastroscopy, grade 2 erosion (66.7%, 118/177 vs43.9%, 25/57; p = 0.002) of gastroscopy and Helicobacter pylori negative (65.4%, 155/237 vs 42.7%, 35/82; p < 0.001) at baseline. For the scores of TCM symptoms in QiruiWeishu group were significantly lower than those in SanjiuWeitai group after 28 days of treatment (p = 0.002). The number and incidence of adverse events related to the trial drug were 14/355 (3.9%) in QiruiWeishu group, 6/118 (5.1%) in SanjiuWeitai group (p > 0.05). No serious adverse reactions occurred in the two groups. According to laboratory tests and ECG, there was no discernible effect on heart, liver, kidney, or blood coagulation function. CONCLUSION: Qirui Weishu capsule appears to be more effective in terms of symptoms than the SanjiuWeitai capsule, and its use is both safe and effective for the treatment of chronic non-atrophic gastritis. A further randomized, double-blind, placebo-control trial is warranted to verify its benefit.

Different dosage regimens of nifedipine, labetalol, and hydralazine for the treatment of severe hypertension during pregnancy: a network meta-analysis of randomized controlled trials.

OBJECTIVES: This network meta-analysis aimed to compare the efficacy and safety of intravenous (IV) hydralazine, oral nifedipine, and IV labetalol with different dosage regimens in the treatment of severe hypertension during pregnancy. METHODS: A comprehensive literature search was performed on PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov for randomized controlled trials (RCTs) exploring the effects of hydralazine, nifedipine, and labetalol in the treatment of severe hypertension during pregnancy. RESULTS: A total of 21 RCTs with 2183 patients comparing 7 regimens (oral nifedipine 50,60,90 mg; hydralazine 15,25 mg; and labetalol 220,300 mg) were identified. Compared with IV labetalol 300 mg, nifedipine 50,60, and 90 mg significantly improved the successful treatment rate of severe hypertension during pregnancy, nifedipine 50 and 90 mg and IV hydralazine 25 mg required significantly fewer doses to achieve target blood pressure (BP), and nifedipine 50 mg took significantly shorter time to achieve target BP. Subgroup analysis showed that only nifedipine 50 mg tablets, not capsules, required a significantly shorter time and fewer doses to achieve target BP than IV labetalol 300 mg. Moreover, nifedipine 60,90 mg showed superior effectiveness than IV hydralazine 15,25 mg in the successful treatment rate of severe hypertension during pregnancy. SUCRA analysis suggested that nifedipine 50,60,90 mg as the better regimens with the lower rates of overall ADR and neonatal complications. CONCLUSION: These findings demonstrated the superiority of oral nifedipine 50,60,90 mg, especially oral nifedipine 50 mg tablets, in the treatment of severe hypertension during pregnancy than IV labetalol 300 mg, while oral nifedipine 60,90 mg also showed superiority in the successful treatment rate of severe hypertension during pregnancy than IV hydralazine 15,25 mg. However, the limitations of the underlying data indicate that future large-scale and rigorous RCTs are needed to confirm such findings.

Compound Tongluo Decoction inhibits endoplasmic reticulum stress-induced ferroptosis and promoted angiogenesis by activating the Sonic Hedgehog pathway in cerebral infarction.

ETHNOPHARMACOLOGICAL RELEVANCE: Cerebral infarction is one of the most common types of cerebrovascular diseases that threaten people's health. Compound Tongluo Decoction (CTLD), a traditional Chinese medicine formula, has various pharmacological activities, including the alleviation of cerebral infarction symptoms. AIM OF THE STUDY: This study aims to explore the potential mechanism by which CTLD alleviates cerebral infarction. MATERIAL AND METHODS: Middle cerebral artery occlusion (MCAO) rat model and oxygen-glucose deprivation and reperfusion (OGD/R) cell model were established for research. The expression of proteins related to endoplasmic reticulum (ER) stress, ferroptosis, Sonic Hedgehog (SHH) pathway and angiogenesis was analyzed by Western blot analysis. The expression of CD31 was detected by immunofluorescence to investigate angiogenesis. In addition, the expression of GRP78 and XBP-1 in brain tissues was investigated by immunohistochemistry. With the application of Prussian blue staining, iron deposition in brain tissue was detected. The levels of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD) were detected using ELISA kits. The angiogenesis was analyzed by tube formation assay. RESULTS: The results presented in this research showed that CTLD and 4-phenyl butyric acid (4-PBA; the inhibitor of ER stress) could alleviate cerebral infarction. Mechanistically, CTLD and 4-PBA rescued ER stress and ferroptosis, but promoted SHH signaling in rats with cerebral infarction. In addition, cerebral infarction exhibited a high level of angiogenesis, which was aggravated by CTLD but suppressed by 4-PBA. Furthermore, CTLD inhibited ER stress and ferroptosis, but promoted SHH signaling and angiogenesis in OGD/R-induced PC12 cells, which was partly abolished by SANT-1, an antagonist of SHH signaling. CONCLUSION: In conclusion, this study revealed that CTLD might inhibit ferroptosis induced by endoplasmic reticulum stress and promote angiogenesis by activating the Sonic Hedgehog pathway in rats with cerebral infarction.

[Preliminary study on cerebrospinal fluid proteomics of Erxian Decoction against neurogenesis impairment in late-onset depression].

This study aims to elucidate the underlying mechanism of Erxian Decoction(EXD) against neurogenesis impairment in late-onset depression(LOD) rats based on cerebrospinal fluid(CSF) proteomics. A total of 66 20-21-month-old male Wistar rats were randomized into naturally aged(AGED) group, LOD group, and EXD group. All rats received chronic unpredictable mild stress(CUMS) for 6 weeks for LOD modeling except for the AGED group. During the modeling, EXD group was given EXD(ig, twice a day at 4 g·kg~(-1)) and other groups received equivalent amount of normal saline(ig). After modeling, a series of behavioral tests, such as sucrose preference test(SPT), open-field test(OFT), forced swimming test(FST), and Morris water maze test(MWMT) were performed. Immunofluorescence method was used to detect the number of Ki-67/Nesti-positive cells and BrdU/DCX-positive cells in the hippocampal DG area of each group. High-concentration corticosterone(CORT) was combined with D-galactose(D-gal) to simulate the changes of LOD-related stress and aging and the proliferation and differentiation of primary neural stem cells of hippocampus in each group were observed. Data independent acquisition(DIA)-mass spectrometry(MS) was used to analyze the differential proteins in CSF among groups and bioinformatics analysis was performed to explore the biological functions of the proteins. Behavioral tests showed that sucrose consumption in SPT, total traveling distance in OFT, and times of crossing the platform in MWMT were all reduced(P<0.01) and the immobility time in FST was prolonged(P<0.01) in the LOD group compared with those in the AGED group, suggesting that LOD rats had developed depression symptoms such as anhedonia, decreased locomotor activity ability, and cognitive dysfunction. Behavioral abnormalities were alleviated(P<0.01, P<0.05) in the EXD group as compared with those in the LOD group. Immunofluorescence results demonstrated that Ki-67/Nesti-positive cells and BrdU/DCX-positive cells in the hippocampal DG area were fewer(P<0.05) in LOD group than in the AGED group, and the positive cells in the EXD group were more(P<0.05) than those in the LOD group. In vitro experiment showed that the proliferation and differentiation of primary hippocampal neural stem cells under the CORT+D-gal treatment were reduced(P<0.01). The proliferation rate of neural stem cells decreased(P<0.05) in CORT+D-gal+LOD-CSF group but increased(P<0.01) in CORT+D-gal+EXD-CSF group compared with that in the CORT+D-gal group. A total of 2 620 proteins were identified from rat CSF, with 135 differential proteins between the LOD group and AGED group and 176 between EXD group and LOD group. GDF11, NrCAM, NTRK2, and GhR were related to neurogenesis and 39 differential proteins were regulated by both LOD and EXD. EXD demonstrated obvious anti-LOD effect, as it improved the locomotor activity ability and cognitive function of LOD rats and protected the proliferation and differentiation of hippocampal neural stem cells. EXD exerts anti-LOD effect by regulating the proteins related to neurogenesis in CSF, such as GDF11, NrCAM, NTRK2, and GhR and maintaining hippocampal neurogenesis.

The proteomics analysis of the effects of Zhishi Rhubarb soup on ischaemic stroke.

BACKGROUND: Stroke has always been a major threat worldwide but is most severe in China, with 2.5 million new stroke cases each year and 7.5 million stroke survivors, placing a heavy burden on the social and national health care systems. Zhishi Rhubarb Soup (ZRS) is a traditional Chinese medicine (TCM) that has been used clinically for many years in China. To explore the potential mechanism of ZRS in the treatment of stroke, liquid chromatography with mass spectrometry (LC-MS) was performed. METHODS: In this study, a quantitative proteomic method with LC-MS was used to analyse the proteomic differences between MACO samples treated with ZRS and those without ZRS treatment. RESULTS: Liquid chromatography with mass spectrometry (LC-MS) analysis led to the identification of 35,006 peptides, with 5160.0 proteins identified and 4094.0 quantified. Significantly differentially expressed proteins were identified through data analysis, and the difference was found to be more than 1.2 times (P < 0.05). The Gene Ontology (GO) analysis provided a summary of the dysregulated protein expression in the biological process (BP), cell component (CC), and molecular function (MF) categories. Proteins related to brain repair, including BDNF, IL-10, IL-6, and TGF-ß, were found to change significantly, partially demonstrating the effectiveness of ZRS to attenuate tissue injury. CONCLUSION: In this study, LC-MS/MS was performed to assess the effects of ZRS on differentially expressed proteins in rats with cerebral infarction. These promising results could help to improve the understanding of the effects of drugs on stroke.

Cerebrospinal fluid proteomics reveal potential protein targets of JiaWeiSiNiSan in preventing chronic psychological stress damage.

CONTEXT: Chinese herbal formula JiaWeiSiNiSan (JWSNS) has been widely used to prevent stress-induced neuropsychiatric ailments in clinics and proven to have therapeutic anti-stress effects on rats. However, the mechanism remains unclear. OBJECTIVE: Based on the proteomics of cerebrospinal fluid (CSF), this study explores the possible mechanism and target proteins of JiaWeiSiNiSan raising stress resilience and preventing stress damage. MATERIALS AND METHODS: A 6-week Chronic Unpredictable Mild Stress (CUMS) model was applied on adult Wistar male rats to observe the effects of JWSNS on improving mental stress resilience. Tandem Mass Tag (TMT) proteomics and bioinformatics analysis were used to screen and analyze differentially expressed proteins (DEPs) in CSF. Parallel Reaction Monitoring (PRM) was used to validate target DEPs. RESULTS: Significantly decreased sucrose preference, locomotion activity level and accuracy of T-maze, as well as increased immobility time, were observed in CUMS rats compared to CON rats while JWSNS improved above depression-like behaviours. The quantitative proteomics and bioinformatics analysis showed that JWSNS decreased the expression of Rps4x, HSP90AA1, Rps12, Uba1, Rsp14, Tuba1b in CUMS rats CSF (p < 0.05, FDR < 0.5). Immunofluorescence results showed that the number of BrdU/DCX positive cells (p < 0.01) and the relative number of neurons (p < 0.01) in the hippocampus dentate gyrus (DG) of the JSWNS group significantly increased, compared with the CUMS group. CONCLUSIONS: JWSNS could increase mental stress resilience and prevent stress damage by regulating proteins in CSF. This study provides a scientific basis for further study on Chinese formulas preventing mental illness.

Ameliorative Effects of Peptides Derived from Oyster (Crassostrea gigas) on Immunomodulatory Function and Gut Microbiota Structure in Cyclophosphamide-Treated Mice.

The intestinal flora is recognized as a significant contributor to the immune system. In this research, the protective effects of oyster peptides on immune regulation and intestinal microbiota were investigated in mice treated with cyclophosphamide. The results showed that oyster peptides restored the indexes of thymus, spleen and liver, stimulated cytokines secretion and promoted the relative mRNA levels of Th1/Th2 cytokines (IL-2, IFN-γ, IL-4 and IL-10). The mRNA levels of Occludin, Claudin-1, ZO-1, and Mucin-2 were up-regulated, and the NF-κB signaling pathway was also activated after oyster peptides administration. Furthermore, oyster peptides treatment reduced the proportion of Firmicutes/Bacteroidetes, increased the relative abundance of Alistipes, Lactobacillus, Rikenell and the content of short-chain fatty acids, and reversed the composition of intestinal microflora similar to that of normal mice. In conclusion, oyster peptides effectively ameliorated cyclophosphamide-induced intestinal damage and modified gut microbiota structure in mice, and might be utilized as a beneficial ingredient in functional foods for immune regulation.

Application of the hospital-family holistic care model in caregivers of patients with permanent enterostomy: A randomized controlled trial.

AIMS: To evaluate the effectiveness of the hospital-family holistic care model based on the theory of 'Timing It Right' in caregivers of patients with permanent enterostomy. DESIGN: A prospective randomized controlled trial. METHODS: One hundred and twenty-five caregivers of patients with permanent enterostomy were recruited from 1 May 2017-31 August 2019. They were randomized into either intervention group (N = 62) or control group (N = 63). The control group received routine care and follow-up, while the intervention group received routine care, follow-up, and hospital-family holistic care intervention based on 'Timing It Right'. The care ability, psychological distress, and life quality of the caregivers were evaluated between the groups before the intervention, at discharge, and 3 and 6 months after discharge. RESULTS: One hundred and eleven caregivers completed the study (88.8%). At 3 and 6 months after discharge, the care ability and life quality in the intervention group were significantly better than those in the control group (t = 8.506/9.783, t = 22.652/26.179, p < 0.05) based on the t tests, and the psychological distress was lower than that in the control group. The ostomy adaptability of the control group was significantly lower than that in the intervention group (p < 0.001) based on the t tests, and the χ2 test showed that ostomy complication was more than that in the intervention group (23.81% vs. 12.90% and 34.92% vs. 19.35%; p < 0.05) at 3 and 6 months after discharge. The interaction between time and group showed that the effect of time factor varied with the group and the four evaluation indexes in the intervention group gradually improved with the extension of the observation time and were better than those in the control group based on generalized estimating equation model. CONCLUSION: The hospital-family holistic care model based on 'Timing It Right' can effectively improve the care ability of caregivers of patients with permanent enterostomy, reduce psychological distress, and improve the quality of life. IMPACT: The caregivers of patients with permanent enterostomy showed dynamic changes in their care experience and needs at different stages of the disease. The hospital-family holistic care intervention strategy based on 'Timing It Right' can effectively improve the caregiver's care ability, alleviate psychological distress, and improve the quality of life. Additionally, improving the patients' stoma adaptability and reducing the incidence of complications related to ostomy.

The association of plasma high-density lipoprotein cholesterol levels and cirrhosis development in obese patients with chronic hepatitis B: a cohort study.

OBJECTIVE: Metabolic disorder is a common risk factor for cirrhosis in Asia, and it will increase the risk of cirrhosis in patients with Chronic hepatitis B (CHB). However, studies on the efficacy of plasma lipid markers which predict the happening and development of cirrhosis in obese CHB patients are limited. METHODS: In total, 3327 patients who were followed for more than 4 years' follow-up in the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine joined the program. Finally, 287 obese CHB patients were included in this study according to the results of metabolic tests. The data of baseline and follow-up were collected, and the association between them was analyzed. RESULTS: Based on the follow-up results, enrolled patients were divided into a group of cirrhosis (n = 146) and a group of noncirrhosis (n = 141). Plasma glucose and high-density lipoprotein cholesterol (HDL-C) levels in the noncirrhosis group (5.2 and 1.2 mmol/L, respectively) were significantly higher than that in the cirrhosis group (5.0 and 1.0 mmol/L, respectively), while the amount of total bile acid (TBA) in the cirrhosis group was lower than that in the cirrhosis group. Levels of HDL-C and total cholesterol were associated with liver function. Plasma HDL-C was an independent indicator of cirrhosis in patients with CHB. Patients with HDL-C levels less than 1.03 mmol/L had a 2.21-fold higher incidence rate of cirrhosis, and patients over 40 years old or the levels of HDL-C less than 1.03 mmol/L were more likely to generate cirrhosis. CONCLUSIONS: Plasma HDL-C was an appropriate marker in predicting cirrhosis for patients with CHB.

Analysis of Functioning and Design of Individualized Rehabilitation Protocol for Children with Learning Disability Using ICF / 中国康复理论与实践

Objective To analyze the overall functioning of children with learning disabilities, and develop individualized exercise rehabilitation protocol using International Classification of Functioning, Disability and Health (ICF). Methods Based on the theoretical framework of ICF and the disease diagnosis of International Classification of Diseases (ICD-11), and with the perspective of child development, the functional profiles of cognition, understanding, attention, thinking, motor, and activity and participation of children with learning disabilities were analyzed. A function-oriented and individulized exercise rehabilitation protocol for children with learning disabilities was constructed in light of ICF bio-psycho-social health paradignm and the theory of somatic and mental interaction. Results The functional performance of children with learning disabilities mainly demonstrated in mental dysfunction in physical functioning in the activities and participation limitations, such as learning and applying knowledge, general tasks and demands, and communication. For the environment factors, products and technology for education, products and technology for culture, recreation and sports, and services, systems and policies could also affect children with learning disabilities. Physical activity was beneficial for children with learning disabilities to improve mental and motor functioning and to effectively enhance intellectual, cognitive, attentional, communication, and mobility skills for the overall development of the children. Physical activity for children with learning disabilities was selected according to WHO guidelines for physical activity and sedentary behavior for children, and moderate to vigorous physical activity for at least 60 minutes, as well as high-intensity training no less than three times a week, together with appropriate physical games and leisure physical activities could effectively improve learning outcomes and reduce learning disabilities. Conclusion The health condition, functioning and motor development of children with learning disability had been analyzed using ICD-11 and ICF, and with the theories of somatic and metal interaction and ICF bio-psycho-social model, the holistic and function-oriented exercise rehabilitation program was developed that recommended at least 60 minutes of moderate intensity physical activity, including aerobic exercise and physical games, per day, and at least three times a week of high intensity physical activity of no less than 30 minutes, including plyometrics and physical competition. The development of individualized function-based exercise rehabilitation programs incorporating the learning disability and motor function characteristics of children could effectively improve the cognitive, attentional, and thinking functions of children with learning disabilities, reduce learning disabilities, and promote the overall development of children.

Analysis of Functioning and Design of Individualized Rehabilitation Protocol for Children with Learning Disability Using ICF / 中国康复理论与实践

Objective To analyze the overall functioning of children with learning disabilities, and develop individualized exercise rehabilitation protocol using International Classification of Functioning, Disability and Health (ICF). Methods Based on the theoretical framework of ICF and the disease diagnosis of International Classification of Diseases (ICD-11), and with the perspective of child development, the functional profiles of cognition, understanding, attention, thinking, motor, and activity and participation of children with learning disabilities were analyzed. A function-oriented and individulized exercise rehabilitation protocol for children with learning disabilities was constructed in light of ICF bio-psycho-social health paradignm and the theory of somatic and mental interaction. Results The functional performance of children with learning disabilities mainly demonstrated in mental dysfunction in physical functioning in the activities and participation limitations, such as learning and applying knowledge, general tasks and demands, and communication. For the environment factors, products and technology for education, products and technology for culture, recreation and sports, and services, systems and policies could also affect children with learning disabilities. Physical activity was beneficial for children with learning disabilities to improve mental and motor functioning and to effectively enhance intellectual, cognitive, attentional, communication, and mobility skills for the overall development of the children. Physical activity for children with learning disabilities was selected according to WHO guidelines for physical activity and sedentary behavior for children, and moderate to vigorous physical activity for at least 60 minutes, as well as high-intensity training no less than three times a week, together with appropriate physical games and leisure physical activities could effectively improve learning outcomes and reduce learning disabilities. Conclusion The health condition, functioning and motor development of children with learning disability had been analyzed using ICD-11 and ICF, and with the theories of somatic and metal interaction and ICF bio-psycho-social model, the holistic and function-oriented exercise rehabilitation program was developed that recommended at least 60 minutes of moderate intensity physical activity, including aerobic exercise and physical games, per day, and at least three times a week of high intensity physical activity of no less than 30 minutes, including plyometrics and physical competition. The development of individualized function-based exercise rehabilitation programs incorporating the learning disability and motor function characteristics of children could effectively improve the cognitive, attentional, and thinking functions of children with learning disabilities, reduce learning disabilities, and promote the overall development of children.