Sarcopenia and coronary heart disease synergistically increase the risk of new onset depressive symptoms in older adults.

BACKGROUND: Coronary heart disease (CHD), sarcopenia and depression are common disorders that markedly impair quality of life and impose a huge financial burden on society. They are also frequently comorbid, exacerbating condition and worsening prognosis. This study aimed to investigate the additive effects of CHD and sarcopenia on the risk of new onset depressive symptoms in older adults. METHODS: The prospective cohort study comprised 897 Chinese community-dwelling participants who were aged 60 years and older (386 men; mean age 66.9 ± 5.9 years) without depressive symptoms at baseline, recruited from Chadian of Tianjin, China. Sarcopenia was defined according to the Asian Working Group for Sarcopenia (AWGS) criteria. CHD was identified via medical records or new diagnosed by at least two physicians. Depressive symptoms were assessed using the Geriatric Depression Scale (GDS) ≥11. Longitudinal data on new onset depressive symptoms were collected up to 12 months after baseline. RESULTS: We found that 103 (11.5%) of the 897 participants without depressive symptoms at baseline had developed depressive symptoms. Participants were classified into mutually exclusive groups based on sarcopenia status and CHD: normal, CHD alone, sarcopenia alone, and co-occurring groups. A logistic regression showed that the CHD alone [odd ratios (OR) = 1.78, 95% confidence interval (CI) = 1.05-3.02], sarcopenia alone (OR = 2.79, 95% CI = 1.26-6.22), and co-occurring (OR = 7.19, 95% CI = 2.75-18.81) had higher risk of depressive symptoms than the normal group after adjusting for the covariates. CONCLUSIONS: CHD and sarcopenia synergistically increase the risk of new onset depressive symptoms in older adults. Thus, older adults may require early detection, and appropriate interventions should be implemented.

Coix seed oil prolongs lifespan and enhances stress resistance in Caenorhabditis elegans.

Coix seed oil (CSO) has many beneficial effects, but there is limited research on its influence on the processes and mechanisms related to senescence. Here, we used Caenorhabditis elegans as an in vivo model to investigate CSO's bioeffects on longevity. CSO (1 mg/mL) significantly extended the mean lifespan of C. elegans by over 22.79% and markedly improved stress resistance. Gene-specific mutant studies showed that the CSO-mediated increase in life expectancy was dependent on mev-1, hsf-1 and daf-16, but not daf-2. Furthermore, CSO significantly upregulated stress-inducible genes, including daf-16 and its downstream genes (sod-3, hsp-16.2 and gst-4). In addition, four major fatty acids, linoleic, oleic, palmitic and stearic, played leading roles in C. elegans' extended lifespan. Thus, CSO increased the life expectancy of, and enhanced the stress resistance in, C. elegans mainly through daf-16 and its downstream genes, but not through the insulin/insulin-like growth factor 1 signaling pathway.

Echinacoside, a phenylethanoid glycoside from Cistanche deserticola, extends lifespan of Caenorhabditis elegans and protects from Aß-induced toxicity.

Cistanche deserticola has been found to exert protection against aging and age-related diseases, but mechanisms underlying its longevity effects remain largely unclear. Here, the multicellular model organism Caenorhabditis elegans was employed to identify lifespan extending and protective effects against ß-amyloid (Aß) induced toxicity by echinacoside (ECH), a phenylethanoid glycoside isolated from C. deserticola. Our results showed that ECH extends the mean lifespan of worms and increases their survival under oxidative stress. Levels of intracellular reactive oxygen species and fat accumulation were also significantly suppressed by ECH. Moreover, ECH-mediated lifespan extension was found to be dependent on mev-1, eat-2, daf-2, and daf-16, but not sir-2.1 or hsf-1 genes. Furthermore, ECH triggered DAF-16 nuclear localization and upregulated two of its downstream targets, sod-3 and hsp-16.2. In addition, ECH significantly improved the survival of CL4176 worms in response to proteotoxic stress induced by Aß protein aggregation. Collectively, these findings suggested that reactive oxygen species scavenging, dietary restriction, and insulin/insulin-like growth factor signaling pathways could be partly involved in ECH-mediated lifespan extension. Thus, ECH may target multiple longevity mechanisms to extend lifespan and have a potency to prevent Alzheimer's disease progression.

Stage IVb thymic carcinoma: patients with lymph node metastases have better prognoses than those with hematogenous metastases.

BACKGROUND: This study aimed to analyze the pattern of lymphogenous and hematogenous metastases in patients with stage IVb thymic carcinomas and identify prognostic factors for their survivals. METHODS: Between September 1978 and October 2014, 68 patients with pathologically confirmed stage IVb thymic carcinomas were treated at Fudan University Shanghai Cancer Center. Forty-three patients had lymph node involvement without distant metastases, and the remaining 25 patients had hematogenous metastases. Clinical-pathological characteristics, including age, sex, histologic subtype, tumor size, metastasis, treatment modalities, such as surgical resection, radiotherapy, and chemotherapy, and clinical outcomes, such as overall survival (OS) and progression free survival (PFS), were analyzed. RESULTS: The median follow-up time was 22 months (range, 1-126 months). The median OS of all patients with stage IVb thymic carcinomas was 30 months, and the 5-year overall survival rate was 25.1%. The median PFS was 11 months, and the 5-year PFS was 17.9%. Stage IVb patients with lymph node involvement had a better survival than those with distant metastasis (40 vs. 20 months, p = 0.002). Patients with myasthenia gravis had a worse prognosis (p = 0.033). Multivariate analysis identified metastatic status as an independent prognostic factor for OS in patients with stage IVb thymic carcinomas. CONCLUSIONS: Patients with lymph node involvement had a better survival than those with distant metastases. Much work remains to investigate the prognosis of patients with stage IVb thymic carcinomas and to explore different treatment strategies for patients with lymph node involvement and distant metastases.

The Protective Effects of HJB-1, a Derivative of 17-Hydroxy-Jolkinolide B, on LPS-Induced Acute Distress Respiratory Syndrome Mice.

Acute respiratory distress syndrome (ARDS),which is inflammatory disorder of the lung, which is caused by pneumonia, aspiration of gastric contents, trauma and sepsis, results in widespread lung inflammation and increased pulmonary vascular permeability. Its pathogenesis is complicated and the mortality is high. Thus, there is a tremendous need for new therapies. We have reported that HJB-1, a 17-hydroxy-jolkinolide B derivative, exhibited strong anti-inflammatory effects in vitro. In this study, we investigated its impacts on LPS-induced ARDS mice. We found that HJB-1 significantly alleviated LPS-induced pulmonary histological alterations, inflammatory cells infiltration, lung edema, as well as the generation of inflammatory cytokines TNF-α, IL-1ß and IL-6 in BALF. In addition, HJB-1 markedly suppressed LPS-induced IκB-α degradation, nuclear accumulation of NF-κB p65 subunit and MAPK phosphorylation. These results suggested that HJB-1 improved LPS-induced ARDS by suppressing LPS-induced NF-κB and MAPK activation.

Seroprevalence of Toxoplasma gondii Among Primary School Children in Shandong Province, China.

Although Toxoplasma gondii infection in primary school children has been investigated in many countries, limited surveys have been available in primary school children in China. In the present study, we report the seroprevalence of T. gondii infection in primary school children in Shandong province, China. Sera from 6,000 primary school children were evaluated for T. gondii antibodies with ELISA. The overall seroprevalence of T. gondii infection was 16.0% (961/6,000), of which 14.5% (870/6,000) were positive for anti-T. gondii IgG antibodies, 3.4% (206/6,000) positive for IgM, and 1.9% (115/6,000) were positive for both IgG and IgM. The results of the present investigation indicated a high seroprevalence of T. gondii infection in primary school children in Shandong province, China. Therefore, effective measures should be taken to prevent and control T. gondii infection in primary school children in this province. To the best of our knowledge, this is the first report of T. gondii seroprevalence in primary school children in Shandong province, China.

Topoisomerase II inhibitors from the roots of Stellera chamaejasme L.

Three new compounds, including one daphnane diterpene (1), one sesquiterpene (6), and one lignan (7) have been isolated from the Stellera chamaejasme L., together with five other known compounds, including four daphnane diterpenenoids (2-5) and one lignan (8). The structures of the new compounds were elucidated by spectroscopic analysis. The cytotoxicities of compounds 1-8 towards human lung adenocarcinoma cells (A549 cells) were evaluated using a sulforhodamine B assay. All of the compounds displayed significant cytotoxicity, with IC50 values in the ranging of 0.2 nM to 2.0 µM. Mechanistic studies revealed that the antitumor activities of compounds 1-3 and 7 were derived from their inhibition of topoisomerase II (Topo II). Furthermore, as a Topo II inhibitor, compound 1 was found to effectively induced G2-M phase cell cycle arrest and apoptosis in cancer cells.

Dendrobium officinale phenolic extract maintains proteostasis by regulating autophagy in a Caenorhabditis elegans model of Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease, and accumulating evidence suggested that proteostatic imbalance is a key feature of the disease. Traditional Chinese medicine exhibits a multi-target therapeutic effect, making it highly suitable for addressing protein homeostasis imbalance in AD. Dendrobium officinale is a traditional Chinese herbs commonly used as tonic agent in China. In this study, we investigated protection effects of D. officinale phenolic extract (SH-F) and examined its underlying mechanisms by using transgenic Caenorhabditis elegans models. We found that treatment with SH-F (50 µg/mL) alleviated Aß and tau protein toxicity in worms, and also reduced aggregation of polyglutamine proteins to help maintain proteostasis. RNA sequencing results showed that SH-F treatment significantly affected the proteolytic process and autophagy-lysosomal pathway. Furthermore, we confirmed that SH-F showing maintainance of proteostasis was dependent on bec-1 by qRT-PCR analysis and RNAi methods. Finally, we identified active components of SH-F by LC-MS method, and found the five major compounds including koaburaside, tyramine dihydroferulate, N-p-trans-coumaroyltyramine, naringenin and isolariciresinol are the main bioactive components responsible for the anti-AD activity of SH-F. Our findings provide new insights to develop a treatment strategy for AD by targeting proteostasis, and SH-F could be an alternative drug for the treatment of AD.

13C-NMR data of daphnane diterpenoids.

Daphnane diterpenoids are mainly distributed in Thymelaeaceae and Euphorbiaceae and have various bioactivities. About 100 daphnane diterpenoids have been isolated from natural plants. In this review, we systematically summarize the (13)C-NMR data of daphnane diterpenoids isolated from natural plants over the past several decades and briefly discussed their biological activities and basic structural-activity relationship.

Characterization of mild or asymptomatic patient admitted with Omicron variant of COVID-19 infection in Tibetan mobile cabin hospital China, August-October 2022.

Background: Prior to August 7, 2022, there had been no positive cases of novel coronavirus in Tibet for 920 consecutive days. However, with the first case of Omicron variant infection, the disease rapidly spread and was prevalent in Tibet for nearly 3 months, from August 7th to November 1st. With the spread of the epidemic, the local government responded quickly and established several mobile cabin hospitals to treat patients with mild and asymptomatic Omicron infection. However, the epidemiological and clinical characteristics of these patients are unknown. Methods: This is a retrospective study including a total of 14,264 mild and asymptomatic cases with Omicron infection in Tibet between August to October, 2022. The clinical data and epidemiological characteristics of COVID-19 cases admitted to Tibet mobile cabin hospitals were collected by using standardized forms from mobile cabin hospital database system, including demographic characteristics, onset symptoms, medication use, past medical history, hospitalization time, and discharge time. In terms of statistical analysis, multivariate Cox regression model was used to analyze the relationship between case characteristics and the length of stay in hospital. Results: Among 14,264 patients infected with Omicron, the average length of hospital stay was six (4-8, Interquartile range) days. Fifty percent of the patients were discharged by the 6th day, and 90% were discharged by the 10th day. Patients of all ages are generally susceptible to COVID-19, and there was no difference in discharge time, but the average length of hospital stay of Tibetan patients with COVID-19 was longer than that of Han patients. According to the statistics of clinical symptoms, sore throat (38.7%) and fever (19.4%) were the most common symptoms, while muscle pain (17.4%), cough (16.6%), and expectoration (13.2%) were also common. In addition, patients with chronic gastritis had significantly longer hospital stays. Conclusion: Based on the experience of Tibet mobile cabin hospitals and data analysis, we believe that patients of all ages are generally susceptible to Omicron. Compared with other novel coronavirus strains, Omicron infected patients had a shorter hospital stay, and treatment of symptoms is expected to shorten the time of nucleic acid negative conversion.

Prognostic values of the prognostic nutritional index, geriatric nutritional risk index, and systemic inflammatory indexes in patients with stage IIB-III cervical cancer receiving radiotherapy.

Background: Growing evidence suggests that nutritional status and inflammation are associated with survival in various cancers. This study aimed to evaluate the prognostic value of the prognostic nutritional index (PNI), geriatric nutritional risk index (GNRI), and systemic inflammatory indexes (neutrophil/lymphocyte ratio [NLR], monocyte/lymphocyte ratio [MLR], and platelet/lymphocyte ratio [PLR]) in patients with stage IIB-III cervical cancer receiving radiotherapy. Results: The ideal cutoff values for the PNI, GNRI, NLR, MLR, and PLR were 48.3, 97.04, 2.8, 0.41, and 186.67, respectively. Low PNI and GNRI scores were associated with poor OS and PFS. High NLR, MLR, and PLR also predicted inferior 5-year OS and PFS rates in patients with stage IIB-III cervical cancer. Multivariate Cox regression analysis identified tumor size, histological type, stage, number of metastatic lymph nodes, PNI, GNRI, NLR, PLR, and MLR as significant prognostic factors for OS and PFS. Conclusions: The current findings suggest that the PNI, GNRI, NLR, PLR, and MLR are essential parameters for predicting prognosis in patients with stage IIB-III cervical cancer receiving radiotherapy.

Liensinine and neferine exert neuroprotective effects via the autophagy pathway in transgenic Caenorhabditis elegans.

BACKGROUND: Liensinine and neferine are the main bisbenzylisoquinoline alkaloids obtained from the seeds of Nelumbo nucifera, which commonly used as edible food and traditional medicine in Asia. It was reported that liensinine and neferine could inhibit the activities of acetylcholinesterase and cross the blood-brain barriers, suggesting their therapeutic potential for the management of Alzheimer's disease. METHODS: Here, we employed SH-SY5Y human neuroblastoma cells stably transfected with the human Swedish amyloid precursor protein (APP) mutation APP695 (APP695swe SH-SY5Y) as an in vitro model and transgenic Caenorhabditis elegans as an in vivo model to investigate the neuroprotective effects and underlying mechanism of liensinine and neferine. RESULTS: We found that liensinine and neferine could significantly improve the viability and reduce ROS levels in APP695swe SH-SY5Y cells, inhibit ß-amyloid and tau-induced toxicity, and enhance stress resistance in nematodes. Moreover, liensinine and neferine had obviously neuroprotective effects by assaying chemotaxis, 5-hydroxytryptamine sensitivity and the integrity of injured neurons in nematodes. Preliminary mechanism studies revealed that liensinine and neferine could upregulate the expression of autophagy related genes (lgg-1, unc-51, pha-4, atg-9 and ced-9) and reduce the accumulation of ß-amyloid induced autophagosomes, which suggested autophagy pathway played a key role in neuroprotective effects of these two alkaloids. CONCLUSIONS: Altogether, our findings provided a certain working foundation for the use of liensinine and neferine to treat Alzheimer's disease based on neuroprotective effects.

Comparison of rectus sheath block and local anesthetic for analgesia in pediatric umbilical hernia repair: A systematic review and meta-analysis.

BACKGROUND: Pediatric umbilical hernia repair could cause considerable postoperative discomfort. This study aimed to compare the analgesia between rectus sheath block and local anesthetic infiltration in child pediatric umbilical hernia repair. METHODS: The relevant randomized controlled trials were searched from PubMed, Embase, Web of Science, EBSCO, and Cochrane library databases from its inception to October 2020. The random-effects model was used for meta-analysis. RESULTS: Four randomized controlled trials were included in the meta-analysis. The 4 studies were published between 2006 and 2017, with sample sizes ranging from 13 to 52 and a total of 143 individuals across the 4 studies. The Jadad scores of the 4 included studies ranged from 4 to 5, and all 4 studies were considered high quality based on quality assessment. There was no difference in analgesic effect at 10 minutes (standardized mean difference [SMD] = -0.19; 95% confidence interval [CI] = -1.52 to 1.16; P = .78), 30 minutes (SMD = -0.37; 95% CI = -1.53 to 0.78; P = .52), 1 hour (SMD = -0.73; 95% CI = -2.00 to 0.53; P = .26) after surgery. Besides, there was no significant difference in postoperative nausea (risk ratio = 0.95; 95% CI = 0.18 to 5.02; P = .95) and postoperative morphine use in morphine equivalents (mean difference = -0.95; 95% CI = -0.06 to 0.01; P = .12). CONCLUSION: Rectus sheath block and local anesthetic are effective methods for analgesia in pediatric umbilical hernia repair.

Dihydro-ß-agarofuran-type sesquiterpenoids from the seeds of Celastrus virens with lifespan-extending effect on the nematode Caenorhabditis elegans.

Twelve dihydro-ß-agarofuran-type sesquiterpenoids, including five new ones (1-5), were purified from the seeds of Celastrus virens (Wang et Tang) C. Y. Chent et T. C. Kao. Their chemical structures were characterized via comprehensive spectroscopic analysis, single-crystal X-ray diffraction analysis, and computational prediction of ECD, as well as comparison of observed and reported NMR spectral data. Among the isolates, nine abundant dihydro-ß-agarofuran-type sesquiterpenoids were evaluated for their lifespan-extending activity using the nematode Caenorhabditis elegans model. As a result, compounds 1, 2, 5, 6, 8, and 9 (50 µM) significantly extended the mean survival time of C. elegans, respectively, compared with the blank control group (p < 0.05). Further Quantitative RT-PCR showed that the prolonging of lifespan mediated by compounds 1, 6, 8, and 9 were dependent on the transcription factors skn-1 and hsf-1.

Acacetin causes a frequency- and use-dependent blockade of hKv1.5 channels by binding to the S6 domain.

We have demonstrated that the natural flavone acacetin selectively inhibits ultra-rapid delayed rectifier potassium current (I(Kur)) in human atria. However, molecular determinants of this ion channel blocker are unknown. The present study was designed to investigate the molecular determinants underlying the ability of acacetin to block hKv1.5 channels (coding I(Kur)) in human atrial myocytes using the whole-cell patch voltage-clamp technique to record membrane current in HEK 293 cells stably expressing the hKv1.5 gene or transiently expressing mutant hKv1.5 genes generated by site-directed mutagenesis. It was found that acacetin blocked hKv1.5 channels by binding to both closed and open channels. The blockade of hKv1.5 channels by acacetin was use- and frequency-dependent, and the IC(50) of acacetin for inhibiting hKv1.5 was 3.5, 3.1, 2.9, 2.1, and 1.7µM, respectively, at 0.2, 0.5, 1, 3, and 4Hz. The mutagenesis study showed that the hKv1.5 mutants V505A, I508A, and V512A in the S6-segment remarkably reduced the channel blocking properties by acacetin (IC(50), 29.5µM for V505A, 19.1µM for I508A, and 6.9µM for V512A). These results demonstrate the novel information that acacetin mainly blocks open hKv1.5 channels by binding to their S6 domain. The use- and rate-dependent blocking of hKv1.5 by acacetin is beneficial for anti-atrial fibrillation.

Polygonum multiflorum Thunb extract extended the lifespan and healthspan of Caenorhabditis elegans via DAF-16/SIR-2.1/SKN-1.

Polygonum multiflorum Thunb (PMT), as a traditional Chinese herbal medicine, has been widely used in the prevention and treatment of aging-related diseases, including Alzheimer's disease, Parkinson's disease, hyperlipidemia, atherosclerosis and inflammation. However, the effect of PMT on the lifespan and its molecular mechanisms are still unclear. Here we found that 60% ethanol refined fraction (PMT-E) of Polygonum multiflorum Thunb at 50 µg mL-1, which contained two main bioactive compounds, 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside (TSG) and emodin-8-O-ß-D-glucoside (EG), could significantly increase the mean lifespan by 19.82%, delay the age-related decline of phenotypes, enhance stress resistance and reduce ROS accumulation in Caenorhabditis elegans. Moreover, we also found that the mitochondrial membrane potential (ΔΨ) and ATP content of worms treated with 50 µg mL-1 PMT-E were obviously improved. Further mechanistic studies revealed that DAF-16, SIR-2.1 and SKN-1 transcription factors were required for PMT-E-mediated lifespan extension. Finally, we found that PMT-E could significantly inhibit the toxicity induced by ß-amyloid (Aß) in Aß transgenic worms. Altogether, these findings laid the foundation for the use of Polygonum multiflorum Thunb to treat aging and age-related diseases.

Agrimophol suppresses RANKL-mediated osteoclastogenesis through Blimp1-Bcl6 axis and prevents inflammatory bone loss in mice.

Excessive activity of osteoclasts causes many bone-related diseases, such as rheumatoid arthritis and osteoporosis. Agrimophol (AGR), a phenolic compound, originated from Agrimonia pilosa Ledeb. In prior studies, AGR is reported to possess schistosomicidal and mycobactericidal activities. However, no reports covered its anti-osteoclastogenesis characteristic. In this study, we found that AGR inhibited RANKL-induced osteoclastogenesis, bone-resorption, F-actin ring formation, and the mRNA expression of osteoclast-associated genes such as CTSK, TRAP, MMP-9, and ATP6v0d2 in vitro. In addition, AGR suppressed RANKL-induced expression of c-Fos and NFATc1. However, AGR treatment did not affect NF-κB activation and MAPKs phosphorylation in RANKL-stimulated BMMs, which implicated that AGR might not influence the initial expression of NFATc1 mediated by NF-κB and MAPKs signaling. Our results further indicated that AGR did not alter phosphorylation levels of GSK3ß and the expression of calcineurin, which implicated that AGR treatment might not interfere with phosphorylation and de-phosphorylation of NFATc1 mediated by GSK3ß and calcineurin, respectively. B-lymphocyte-induced maturation protein-1 (Blimp1), which was regarded as a transcriptional repressor of negative regulators of osteoclastogenesis, was markedly attenuated in the presence of AGR, leading to the enhanced expression of B-cell lymphoma 6 (Bcl-6). Meanwhile, Blimp1 knockdown in BMMs by siRNA strongly enhanced the expression of Bcl6 and reduced NFATc1 induction by RANKL. These findings suggested that AGR inhibited RANKL-induced osteoclast differentiation through Blimp1-Bcl-6 signaling mediated modulation of NFATc1 and its target genes. Consistent with these in vitro results, AGR exhibited a protective influence in an in vivo mouse model of LPS-induced bone loss by suppressing excessive osteoclast activity and attenuating LPS-induced bone destruction. Hence, these results identified that AGR could be considered as a potential therapeutic agent against bone lysis disease.

Diterpenoids from the roots of Euphorbia fischeriana.

Six tigliane-type diterpenoids (1-6) were isolated from the roots of Euphorbia fischeriana. Their structures were elucidated by various spectral analyses. Among them, compounds 1 and 3 were new, and compounds 2, 4, and 5 were naturally obtained for the first time. All compounds were tested against two human cancer cell lines, MDA-MB-231 and HepG2, and one human immortalized cell line, and only compound 6 showed cytotoxicity for MDA-MB-231 cells with an IC(50) value of 6.694 µM.

[A multi-center randomized controlled trial on treatment of diarrhea-predominant irritable bowel syndrome by Chinese medicine syndrome-differentiation therapy].

OBJECTIVE: To verify the clinical efficacy of Chinese Medicine syndrome-differentiation therapy in treating diarrhea-predominant irritable bowel syndrome IBS-D. METHODS: With a blinded randomized controlled design adopted, 360 patients with IBS-D were randomly assigned to two groups, the treated group and the control group, they were treated with Chinese medicine and Pinaverium bromide for four weeks respectively. RESULTS: Comprehensive evaluation showed that the total effective rate in the treated group was higher than that in the control group significantly (93.8% vs 81.3%, P<0.01). Efficacy assessment on symptoms (by scoring) showed that the efficacy in the treated group was better than that in the control group in aspects of improving abdominal pain (86.1% vs 70.3%), defecation coziness (involving the frequency of defecation, incidence of tenesmus in the latest 10 days and Bristol typing of stool characters), living interfering, and total BSS score (P<0.05 or P<0.01). CONCLUSION: Chinese medicine syndrome-differentiation dependent therapy shows good efficacy in treating IBS-D.