Modified Guo-Min decoction ameliorates PM2.5-induced lung injury by inhibition of PI3K-AKT and MAPK signaling pathways.

BACKGROUND/PURPOSE: Exposure to particles with an aerodynamic diameter of ≤2.5 µm (PM2.5) increased various lung diseases, which lack effective treatment. Massive evidence links PM2.5 to the development of allergic lung diseases like asthma. Modified Guo-Min Decoction (MGMD) is a traditional Chinese formula for allergic diseases. However, whether MGMD could improve PM2.5-induced lung injury and the underlying mechanism remain unclear and we aimed to explore. STUDY DESIGN/METHODS: Male Wistar rats (200-220 g) were intratracheally instilled of PM2.5 suspension daily for 4 weeks to establish PM2.5-induced lung injury model. MGMD (2.1 g/kg) treatment by gavage was started 1 week before, at the same time or 1 week after the instillation of PM2.5 suspension, namely the pre-, sync- or post-administration groups. HE and Masson staining were used to observe morphological changes. Immunohistochemistry staining was used to detect macrophage and neutrophil infiltration. The levels of inflammatory cytokines in the bronchoalveolar lavage fluid were detected by ELISA. The main components of MGMD were detected by UHPLC-LTQ-Orbitrap MSn. Network pharmacology was used to identify the key targets mediating the effect of MGMD in treating PM2.5-induced lung injury. Changes in the expression of target proteins were examined by western blot. In-vitro experiments were carried out in Beas2b cells to evaluate the protective effect and mechanism of MGMD against PM2.5 induced injury. RESULTS: Exposure to PM2.5 suspension resulted in disarrangement of tracheal epithelium, neutrophil and M1 macrophage infiltration and collagen deposition, and significantly increased IgE, IL-1ß and IL-17 secretion and NLRP3 expression, which were inhibited by MDMD treatment and pre-MGMD treatment showed the best effect. By UHPLC-LTQ-Orbitrap MSn, 46 main compounds were identified in MGMD. Using network pharmacology approach, we found MGMD attenuate PM2.5-induced lung damage by targeting 216 genes, and PPI network, GO and KEGG analysis all indicated that PI3K-AKT and MAPK pathways were important. Western blot showed that PM2.5 suspension exposure increased PI3K, AKT, ERK and JNK phosphorylation, which were reversed by MGMD intervention significantly. In vitro, the viability of Beas2b cells was significantly decreased after PM2.5 suspension exposure, and was obviously upregulated after MGMD-containing serum or LY294002 treatment. CONCLUSION: The present study demonstrated that MGMD could improve PM2.5-induced lung injury through reducing inflammation and pulmonary fibrosis, which was probably mediated by inhibition of the PI3K-AKT and MAPK signaling pathways, and NLRP3 inflammasome. The results of this study support and provide scientific evidence for the clinical application of MGMD on PM2.5-induced lung injury. Pre-treatment, sync-treatment, and post-treatment is the highlight of this study.

Influence of transcutaneous electrical nerve stimulation on the distance walked by older adults during the 6-min test of walking endurance.

The purpose of our study was to compare the influence of two types of transcutaneous electrical nerve stimulation (TENS) on the performance of older adults on the 6-min test of walking endurance and on the ability to maintain balance during upright standing. Twenty-six healthy older adults (72 ± 5.4 yrs) performed tests of motor function while TENS was applied to the tibialis anterior and rectus femoris muscles of each leg. Linear mixed models were used to compare the influence of TENS on walking distance in a 6-min test of walking endurance and on sway-area rate in tests of standing balance. There was a significant decrease in the distances walked in each minute of the 6-min walk test for both the Continuous and Burst TENS modes compared with Baseline (p < 0.01 and p < 0.001, respectively). The influence of TENS on walking distance was associated with several significant effects on the mean and coefficient of variation for stride length and stride frequency between the first and last minute of the test and between the two TENS modes and the Baseline values. In contrast, there was no significant effect of TENS on sway-area rate in any balance test, which indicates that the supplementary sensory feedback compromised walking performance of older adults but not the ability to maintain balance during upright standing.

Tuo-Min-Ding-Chuan Decoction Alleviates Airway Inflammations in the Allergic Asthmatic Mice Model by Regulating TLR4-NLRP3 Pathway-Mediated Pyroptosis: A Network Pharmacology and Experimental Verification Study.

Background: Tuo-Min-Ding-Chuan Decoction (TMDCD) is an effective traditional Chinese medicine (TCM) formula granule for allergic asthma (AA). Previous studies proved its effects on controlling airway inflammations, while the specific mechanism was not clear. Methods: We conducted a network pharmacology study to explore the molecular mechanism of TMDCD against AA with the public databases of TCMSP. Then, HUB genes were screened with the STRING database. DAVID database performed GO annotation and KEGG functional enrichment analysis of HUB genes, and it was verified with molecular docking by Autodock. Then, we built a classic ovalbumin-induced allergic asthma mice model to explore the mechanism of anti-inflammation effects of TMDCD. Results: In the network pharmacology study, we found out that the potential mechanism of TMDCD against AA might be related to NOD-like receptor (NLR) signaling pathway and Toll-like receptor (TLR) signaling pathway. In the experiment, TMDCD showed remarkable effects on alleviating airway inflammations, airway hyperresponsiveness (AHR), and airway remodeling in the asthmatic mice model. Further molecular biology and immunohistochemistry experiments suggested TMDCD could repress TLR4-NLRP3 pathway-mediated pyroptosis-related gene transcriptions to inhibit expressions of target proteins. Conclusion: TMDCD could alleviate asthmatic mice model airway inflammations by regulating TLR4-NLRP3 pathway-mediated pyroptosis.

Influence of transcutaneous electrical nerve stimulation on walking kinematics and standing balance of older adults who differ in walking speed.

The purpose was to determine the impact of transcutaneous electrical nerve stimulation (TENS) on measures of walking kinematics and standing balance of healthy older adults who were stratified into two groups based on differences in the distance walked during the 6-min test of walking endurance. Regression models were developed to explain the variance in the 6-min distance and to assess the predictive power of balance metrics to categorize the 26 older adults (72 ± 5.4 yrs) as either slow or fast walkers. Walking kinematics were measured during 6- and 2-min walk tests that were performed with and without the concurrent application of TENS to the hip flexor and ankle dorsiflexor muscles. Participants walked briskly during the 6-min test and at a preferred pace during the 2-min test. The supplementary sensory stimulation provided by TENS did not alter the power of the models to explain the variance in the Baseline 6-min distance: Baseline, R2 = 0.85; TENS, R2 = 0.83. In contrast, TENS improved the explanatory power of the data obtained during the 2-min walk to account for the variance in the Baseline 6-min distance: no TENS, R2 = 0.40; TENS, R2 = 0.64. Logistic regression models based on force-plate and kinematic data obtained during the balance tasks were able to discriminate between the two groups with excellent certainty. The impact of TENS was greatest when older adults walked at a preferred speed but not when they walked at a brisk pace or performed tests of standing balance.

Potential impacts of siltation by Spartina alterniflora on nutrient dynamics in its decomposing litters in coastal marsh of the Min River estuary, southeast China.

The Spartina alterniflora started to invade the Min River estuary (Southeast China) in 2002 and, thereafter, its invasion area showed an increasing trend. Since the siltation depths caused by S. alterniflora in the Min River estuary were much higher (4.8-7.2 cm yr-1) than the values reported in other coastal regions of China (3.5-6.5 cm yr-1), the impacts of siltation on nutrient cycle processes in this region might be more evident. In order to explore the potential effects of siltation by S. alterniflora on nutrient ((carbon (C), nitrogen (N), phosphorous (P) and sulfur (S)) variations in its decaying litters, three one-off siltation treatments (no siltation scenario (0 cm yr-1, NSS), current siltation scenario (5 cm yr-1, CSS) and strong siltation scenario (10 cm yr-1, SSS)) were designed in coastal marsh of the Min River estuary and the in-situ decomposition experiment was conducted from February 2016 to February 2017 by litterbag technique. Results showed that the siltation caused by S. alterniflora showed significant impact on its decomposition rate, following the sequence of NSS (0.005638 d-1) > SSS (0.003005 d-1) > CSS (0.002478 d-1) (p < 0.05). The total carbon (TC) contents in decomposing litters in the three siltation treatments showed dissimilar fluctuations and significantly higher values were observed in the CSS and SSS treatments compared to the NSS treatment. The contents of total nitrogen (TN) and total sulfur (TS) in decomposing detritus in the three siltation treatments generally showed increasing trend during the whole decomposition, while those of total phosphorus (TP) showed increasing trend after decomposing for 30 days. The differences in nutrient variations among the three siltation treatments, to a great extent, rested with the alterations of substrate quality in detritus during the experiment. Although the stocks of C, N, P and S in detritus in the three siltation treatments evidenced the release from litters to the surroundings during decomposition, the release amounts of these nutrients in some periods were at a lower level. With increasing siltation depths, the release of C, N and P from detritus was generally restrained during the whole decomposition, while that of S from decaying litters was inhibited only at the late stage of decomposition. This paper found that the siltation caused by S. alterniflora reduced the nutrient return (particularly for C, N and P) from its detritus, which, in turn, might greatly alter the nutrient cycle in S. alterniflora marsh.

Commiphora myrrha stimulates insulin secretion from ß-cells through activation of atypical protein kinase C and mitogen-activated protein kinase.

ETHNOPHARMACOLOGICAL RELEVANCE: Ayurvedic medicine has been used in the treatment of diabetes mellitus for centuries. In Arabia and some areas of Africa, Commiphora myrrha (CM) has been extensively used as a plant-based remedy. We have previously shown that an aqueous CM resin solution directly stimulates insulin secretion from MIN6 cells, a mouse ß-cell line, and isolated mouse and human islets. However, the signaling pathways involved in CM-induced insulin secretion are completely unknown. Insulin secretion is normally triggered by elevations in intracellular Ca2+ ([Ca2+]i) through voltage gated Ca2+ channels (VGCC) and activation of protein kinases. Protein and lipid kinases such as protein kinase A (PKA), Ca2+-calmodulin dependent protein kinase II (CaMKII), phosphoinositide 3-kinases (PI3Ks), protein kinase C (PKC) and mitogen-activated protein kinase (MAPK), specifically extracellular signal-regulated kinases (ERK1/2), may be involved in receptor-operated insulin secretion. Therefore, we hypothesized that CM may induce insulin secretion by modulating the activity of VGCC and/or one or more of the above kinases. AIM OF THE STUDY: To investigate the possible molecular mechanism of action of CM-induced insulin secretion. The effects of aqueous CM resin extract on [Ca2+]i and protein kinase activation from ß-cells were examined. METHODS: The effect of aqueous CM resin solution on [Ca2+]i was assessed using Ca2+ microfluorimetry. The involvement of VGCC in CM-induced insulin secretion was investigated using static and perifusion insulin secretion experiments in the presence of either EGTA, a Ca2+ chelator, or nifedipine, a blocker of VGCC. The involvement of kinase activation in the stimulatory effect of CM on insulin secretion was examined by using static and perifusion insulin secretion experiments in the presence of known pharmacological inhibitors and/or downregulation of specific kinases. The effects of CM on phosphorylation of PKCζ and ERK1/2 were also assessed using the Wes™ capillary-based protein electrophoresis. RESULTS: Ca2+ microfluorimetry measurements showed that exposing MIN6 cells to CM (0.5-2 mg/mL) was not associated with changes in [Ca2+]i. Similarly, incubating MIN6 cells and mouse islets with EGTA and nifedipine, respectively, did not attenuate the insulin secretion induced by CM. However, incubating mouse and human islets with CM in the presence of staurosporine, a non-selective protein kinase inhibitor, completely blocked the effect of CM on insulin secretion. Exposing mouse islets to CM in the presence of H89, KN62 and LY294002, inhibitors of PKA, CaMKII and PI3K, respectively, did not reduce CM-induced insulin secretion. However, incubating mouse and human islets with CM in the presence of Ro 31-8220, a pan-PKC inhibitor, diminished insulin secretion stimulated by CM, whereas inhibiting the action of typical PKC (with Go6976) and PLCß (with U73122) did not affect CM-stimulated insulin secretion. Similarly, downregulating typical and novel PKC by chronic exposure of mouse islets to phorbol 12-myristate 13-acetate (PMA) was also not associated with a decrease in the stimulatory effect of CM on insulin secretion. Interestingly, CM-induced insulin secretion from mouse islets was inhibited in the presence of the PKCζ inhibitor ZIP and a MAPK inhibitor PD 98059. In addition, Wes™ capillary-based protein electrophoresis indicated that expression of the phosphorylated forms of PKCζ and ERK1/2, a MAPK, was significantly increased following exposure of INS-1832/13 cells, a rat insulinoma cell line, to CM. CONCLUSIONS: Our data indicate that CM directly stimulates insulin secretion through activating known downstream effectors of insulin-stimulus secretion coupling. Indeed, the increase in insulin secretion seen with CM is independent of changes in [Ca2+]i and does not involve activation of VGCC. Instead, the CM stimulatory effect on insulin secretion is completely dependent on protein kinase activation. Our findings indicate that CM could induce insulin exocytosis by stimulating the phosphorylation and activation of PKCζ, which in turn phosphorylates and activates ERK1/2.

Medication and prescription rules for treating spleen and stomach diseases in Prescriptions of Peaceful Benevolent Dispensary / 数字中医药（英文）

@#【Objective】   To explore the prescriptions related to the treatment of spleen and stomach diseases in Prescriptions of Peaceful Benevolent Dispensary (Tai Ping Hui Min He Ji Ju Fang,《太平惠民和剂局方》, TPHMHJJF), and investigate the medication and prescription rules. 【Methods】   The prescriptions of TPHMHJJF for treating spleen and stomach diseases were screened, and the data set was established by entering the prescriptions and standardized drug names using WPS Excel 2019. Herb frequency statistics, efficacy categorization, property, flavor, meridian tropism, association rules, cluster analysis, factor analysis, and complex network analysis were performed using Python 3.6.8 programming language and Gephi 0.9.2 visualization software. 【Results】   A total of 239 prescriptions were included after the screening, and the dosage forms were mainly pills and powders. The study involved 200 herbal medicines, among which 40 herbs had a frequency of ≥ 12. The herb with the highest frequency was Ganjiang (Zingiber Rhizoma). The herb properties were mainly warm in nature, with the most pungent herbs. Most herbs were attributed to the spleen and stomach meridians, and tonifying medicine were the main species. The association rule analysis identified 26 second-order association rules and 16 third-order association rules, with "Renshen (Ginseng Radix et Rhizoma) → Fuling (Poria)" as the leading rule in the former and "Fuling (Poria) + Baizhu (Atractylodis Macrocephalae Rhizome) → Renshen (Ginseng Radix et Rhizoma)" as the leading rule in the latter. Also, cluster analysis divided the top 30 herbs into six herb combinations that can warm the middle, move Qi, and dry dampness effectively. Factor analysis extracted 13 common factors, with Renshen (Ginseng Radix et Rhizoma), Fuling (Poria), and Baizhu (Atractylodis Macrocephalae Rhizome) as the highest contributing factors. Lastly, complex network analysis yielded the core prescription of 14 herbs, with Ganjiang (Zingiber Rhizoma), Renshen (Ginseng Radix et Rhizoma), Gancao (Glycyrrhizae Radix et Rhizome), and Chenpi (Citri Reticulatae Pericarpium) among the herbs with a higher weighting degree. 【Conclusion】  TPHMHJJF is mainly based on the use of warming herbs to treat spleen and stomach diseases, and its medication rule can be summarized into three aspects: (i) primarily using warming and tonifying to warm the middle and dissipate cold, (ii) using the method of moving Qi with aromatic nature to delight the spleen and appetize the stomach, and (iii) emphasizing the regulation of Qi and blood to calm the five zang-organs.

Effects of l-Arginine Plus Vitamin C Supplementation on Physical Performance, Endothelial Function, and Persistent Fatigue in Adults with Long COVID: A Single-Blind Randomized Controlled Trial.

Long COVID, a condition characterized by symptom and/or sign persistence following an acute COVID-19 episode, is associated with reduced physical performance and endothelial dysfunction. Supplementation of l-arginine may improve endothelial and muscle function by stimulating nitric oxide synthesis. A single-blind randomized, placebo-controlled trial was conducted in adults aged between 20 and 60 years with persistent fatigue attending a post-acute COVID-19 outpatient clinic. Participants were randomized 1:1 to receive twice-daily orally either a combination of 1.66 g l-arginine plus 500 mg liposomal vitamin C or a placebo for 28 days. The primary outcome was the distance walked on the 6 min walk test. Secondary outcomes were handgrip strength, flow-mediated dilation, and fatigue persistence. Fifty participants were randomized to receive either l-arginine plus vitamin C or a placebo. Forty-six participants (median (interquartile range) age 51 (14), 30 [65%] women), 23 per group, received the intervention to which they were allocated and completed the study. At 28 days, l-arginine plus vitamin C increased the 6 min walk distance (+30 (40.5) m; placebo: +0 (75) m, p = 0.001) and induced a greater improvement in handgrip strength (+3.4 (7.5) kg) compared with the placebo (+1 (6.6) kg, p = 0.03). The flow-mediated dilation was greater in the active group than in the placebo (14.3% (7.3) vs. 9.4% (5.8), p = 0.03). At 28 days, fatigue was reported by two participants in the active group (8.7%) and 21 in the placebo group (80.1%; p < 0.0001). l-arginine plus vitamin C supplementation improved walking performance, muscle strength, endothelial function, and fatigue in adults with long COVID. This supplement may, therefore, be considered to restore physical performance and relieve persistent symptoms in this patient population.

Effect of Ferric Carboxymaltose Supplementation in Patients with Heart Failure with Preserved Ejection Fraction: Role of Attenuated Oxidative Stress and Improved Endothelial Function.

Both clinical and experimental evidence shows that iron deficiency (ID) correlates with an increased incidence of heart failure (HF). Moreover, data on iron supplementation demonstrating a beneficial effect in subjects with HF have mostly been collected in patients undergoing HF with reduced ejection fraction (HFrEF). Relatively poor data, however, exist on the potential of iron supplementation in patients with HF with preserved ejection fraction (HFpEF). Here, we report on data emerging from a multicentric, double-blind, randomized, placebo-controlled study investigating the effect of IV supplementation with a placebo or ferric carboxymaltose (FCM) on 64 subjects with HFpEF. ID was detected by the measurement of ferritin levels. These data were correlated with cardiac performance measurements derived from a 6 min walking test (6MWT) and with echocardiographic determinations of diastolic function. Moreover, an EndoPAT analysis was performed to correlate cardiac functionality with endothelial dysfunction. Finally, the determination of serum malondialdehyde (MDA) was performed to study oxidative stress biomarkers. These measurements were carried out before and 8 weeks after starting treatment with a placebo (100 mL of saline given i.v. in 10 min; n = 32) or FCM at a dose of 500 mg IV infusion (n = 32), which was given at time 0 and repeated after 4 weeks. Our data showed that a condition of ID was more frequently associated with impaired diastolic function, worse 6MWT and endothelial dysfunction, an effect that was accompanied by elevated MDA serum levels. Treatment with FCM, compared to the placebo, improved ferritin levels being associated with an improved 6MWT, enhanced cardiac diastolic function and endothelial reactivity associated with a significant reduction in MDA levels. In conclusion, this study confirmed that ID is a frequent comorbidity in patients with HFpEF and is associated with reduced exercise capacity and oxidative stress-related endothelial dysfunction. Supplementation with FCM determines a significant improvement in diastolic function and the exercise capacity of patients with HFpEF and is associated with an enhanced endothelial function and a reduced production of oxygen radical species.

Bicycle ergometer exercise during hemodialysis and its impact on quality of life, aerobic fitness and dialysis adequacy: A pilot study.

BACKGROUND: Chronic kidney disease patients on hemodialysis commonly have a worse quality of life (QoL) due to complications of the disease and dialysis procedure. Physical exercise has emerged as a strategy to improve this scenario. The objective of this study was to evaluate the effect of an intradialytic aerobic exercise program on QoL and aerobic fitness in hemodialysis patients. MATERIAL AND METHODS: These are a secondary analysis of clinical trial data previously published in which hemodialysis patients were randomized into "bike group" (using an adapted exercise bicycle) or "control group" (usual care). The exercise sessions lasted 45 min (5 min of warm-up, 35 min of moderate-intensity and 5 min of cool-down) three times/week for three months. The QoL domains were assessed using the SF-36 QoL questionnaire. Aerobic fitness was evaluated using the 6-min walk test (6MWT). Circulating cytokines, biochemical parameters and Kt/V were also assessed. RESULTS: Nine patients completed three months of exercise (5 men, 44 ± 11 years), and nine were in the control group (6 men, 44 ± 14 years). In the bike group, there was a trend to improve the physical role domain (p = 0.06) regarding QoL, an improvement in the 6MWT (p = 0.02), and in the Kt/V (p = 0.03) after three months. There was a positive correlation between the general health domain and Kt/V (r = 0.691; p = 0.003) and an inverse correlation between the physical functioning domain and plasma TNF-α levels (r = -0.514; p = 0.04). CONCLUSIONS: 12 weeks of intradialytic aerobic exercise was enough to benefit hemodialysis patients' quality of life, aerobic fitness, and quality of dialysis. CLINICALTRIALS: gov id: NCT04375553.

Laser acupuncture for claudication symptoms in peripheral artery disease - Does it work? A randomized trial.

Background: Peripheral artery disease (PAD) receives little attention despite its clinical consequences. Intermittent claudication is the most disturbing symptom of the disease resulting in marked limitations to functional walking performance. Treadmill walking exercise is the first-line non-pharmacological treatment in PAD; however, older patients may be unable to exercise because of the functional disability of the disease itself or deconditioning. Objective: In an attempt to seek an alternative intervention, this study aimed to assess the effect of laser acupuncture on patient-reported claudication symptoms and walk performance in PAD. Methods: Thirty male patients with PAD were assigned randomly to a control group ( n 1 = 15 , 64 . 5 ± 3 . 5 years old, 25 . 9 ± 2 . 6 kg/m2) or a study group ( n 2 = 15 , 65 . 6 ± 3 . 3 years old, 25 . 44 ± 3 . 1 kg/m2). Inclusion criteria were mild-to-moderate PAD, Fontaine stage II, unilateral or bilateral claudications, and older men. Exclusion criteria were asymptomatic PAD, resting pain, severe or critical limb ischemia, ischemic ulcers, and patients contraindicated for laser therapy. Both groups received pharmacological treatment, but only the study group received gallium aluminum arsenide (GaAlAs) laser therapy at nine acupuncture points, namely, Liver 2 (LV2), Stomach 41 (ST41), Urinary bladder 40 (UB40), UB60, UB61, Gall bladder 30 (GB30), GB34, GB38, and GB40 for 2 days/week and five consecutive weeks. A pen-type laser device was used at a wavelength of 654 . 7 ± 2 nm, with a power output of 41 ± 3 . 65 mW, a spot size of 0.08 cm2, and an energy density of 2 J/cm2, for 60 s/point. The Edinburgh Claudication Questionnaire (ECQ) and the 6-min walk distance (6-MWD) were the endpoints of the study. The McNemar-Bowker Test and Generalized Estimating Equations Ordinal Logistic Regression Model were used for the within- and between-group statistical analyses of the categorical data of ECQ, respectively; and a mixed model MANOVA was used for the within- and between-group analyses of the 6-MWD data. Results: There was a significant improvement in patients' response to ECQ only in the study group compared to the baseline ( p = 0 . 002 ) and the controls ( p < 0 . 001 ) after the intervention. The 6-MWD increased significantly in the study group compared to the baseline ( 318 ± 77 m versus 214 ± 60 m, p < 0 . 001 ). Conclusion: The GaAlAs laser acupuncture applied at selected acupoints may be a promising intervention complementary to drug therapy that could help relieve claudication symptoms and improve physical functional performance in older men with PAD (Fontaine stage II). Trials were conducted under the Trial Registration No. PACTR201912698539774.

Development and Validation of a Clinical Prediction Model for Complicated Appendicitis in the Elderly.

Background: For elderly patients with mild clinical symptoms of uncomplicated appendicitis(UA), non-surgical treatment has been shown to be feasible, whereas emergency surgical treatment is recommended in elderly patients with complicated appendicitis(CA), but it is still challenging to accurately distinguish CA and UA before treatment. This study aimed to develop a predictive model to assist clinicians to quickly determine the type of acute appendicitis. Methods: We retrospectively studied the clinical data of elderly patients with acute appendicitis who visited the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine from January 2012 to January 2022. The patients were divided into UA group and CA group, and the general conditions, medical history, physical examination, laboratory examination and imaging examination were compared between the two groups, and SPSS 26.0 and R 4.0.2 software were used to establish CA clinic. Predict the model, and validate it internally. Results: The clinical data of 441 elderly patients with acute appendicitis were collected, 119 patients were excluded due to incomplete clinical data or other diseases. Finally, 332 patients were included in the study and divided into UA group (n = 229) and CA group (n = 103). By analyzing the clinical data of the two groups of patients, the duration of abdominal pain [OR = 1.094, 95% CI (1.056-1.134)], peritonitis [OR = 8.486, 95% CI (2.017-35.703))] and total bilirubin [OR = 1.987, 95% CI (1.627-2.426)] were independent predictors of CA (all p < 0.01). The model's Area Under Curve(AUC) = 0.985 (95% CI, 0.975-0.994). After internal verification by Bootstrap method, the model still has high discriminative ability (AUC = 0.983), and its predicted CA curve is still in good agreement with the actual clinical CA curve. Conclusion: We found that a clinical prediction model based on abdominal pain duration, peritonitis, and total bilirubin can help clinicians quickly and effectively identify UA or CA before treatment of acute appendicitis in the elderly, so as to make more scientific clinical decisions.

Anti-Inflammatory and Anti-asthmatic Effects of TMDCT Decoction in Eosinophilic Asthma Through Treg/Th17 Balance.

Tuo-Min-Ding-Chuan decoction (TMDCT) is a Traditional Chinese Medicine (TCM) formula consisting of twelve herbs that can relieve the symptoms and treat allergic asthma. Yet, the underlying mechanism of action is still unclear. In this study, we investigated the effect of TMDCT in regulating Treg/Th17 cells immune balance and explored potential metabolic and gut biomarkers associated with Treg and Th17 cells in eosinophilic asthma mice treated by TMDCT. We found that TMDCT increases Treg cells percentage and decreases Th17 cells percentage in the ovalbumin (OVA) -induced eosinophilic asthma mice model. Furthermore, Imidazoleacetic acid, dL-glutamine, L-pyroglutamic acid, 2-deoxy-d-glucose were preliminary identified as biomarkers in plasma metabolites treated by TMDCT, meanwhile genus Desulfovibrio, genus Butyricimonas and genus Prevotella 9 were preliminary identified as gut microbiota biomarkers after TMDCT treatment. These results provide an experimental foundation for the treatment of allergic asthma with Chinese herbal compounds.

Traditional Patchouli essential oil modulates the host's immune responses and gut microbiota and exhibits potent anti-cancer effects in ApcMin /+ mice.

Patchouli Essential Oil (PEO) has been used as a scent for various healing purposes since the ancient Egyptian period. The primary source of the oil is Pogostemon cablin (PC), a medicinal plant for treating gastrointestinal symptoms. However, the pharmacological function has not been addressed. Here, we report the cancer prevention and gut microbiota (GM) modulating property of PEO and its derivatives patchouli alcohol (PA) and pogostone (PO) in the ApcMin /+ colorectal cancer mice model. We found that PEO, PA, and PO significantly reduced the tumor burden. At the same time, it strengthened the epithelial barrier, evidenced by substantially increasing the number of the goblet and Paneth cells and upregulation of tight junction and adhesion molecules. In addition, PEO, PA, and PO shifted M1 to M2 macrophage phenotypes and remodeled the inflammatory milieu of ApcMin /+ mice. We also found suppression of CD4+CD25+ and stimulation CD4+ CD8+ cells in the spleen, blood, mesenteric lymph nodes (MLNs), and Peyer's patches (PPs) of the treated mice. The composition of the gut microbiome of the drug-treated mice was distinct from the control mice. The drugs stimulated the short-chain fatty acids (SCFAs)-producers and the key SCFA-sensing receptors (GPR41, GPR43, and GPR109a). The activation of SCFAs/GPSs also triggered the alterations of PPAR-γ, PYY, and HSDCs signaling mediators in the treated mice. Our work showed that PEO and its derivatives exert potent anti-cancer effects by modulating gut microbiota and improving the intestinal microenvironment of the ApcMmin /+ mice.

Selenomethionine modulates insulin secretion in the MIN6-K8 mouse insulinoma cell line.

Selenium is an essential trace element of interest for its potential role in glucose homeostasis. The present study investigated the impact of selenium supplementation as selenomethionine (SeMet) on insulin secretion in MIN6-K8 cells, a pancreatic ß-cell model. We found that SeMet enhanced percent glucose-induced insulin secretion, while also increasing tolbutamide- and KCl-induced percent insulin secretion. RNA-sequencing showed that SeMet supplementation altered expression of several selenoproteins, including glutathione peroxidase 3 (Gpx3) and selenoprotein P (SelP). Targeted knockdown of Gpx3 increased both percent and total insulin release, while SelP knockdown increased insulin content and insulin release. Collectively, these studies support a putative role for selenium and selenoproteins in the regulation of insulin secretion, glucose homeostasis, and diabetes risk.

[Theoretic analysis on twirling acupuncture manipulation for reinforcing and reducing in treatment of hypertension by academician SHI Xue-min].

The paper explains academician SHI Xue-min's understanding on hypertension and the concrete application of twirling acupuncture technique for reinforcing and reducing in treatment of hypertension, and explores the theoretic basis of the first and second definitions of twirling acupuncture technique for reinforcing and reducing proposed by the academician SHI Xue-min. It is believed that the dysfunction of the sea of qi and the disharmony of the liver and spleen are the etiologies of hypertension, thus, the treatment principles are suggested as "activating blood circulation, dispersing wind, smoothing liver qi and strengthening spleen functions". Renying (ST 9) is selected as the main acupoint, while Hegu (LI 4), Taichong (LR 3), Quchi (LI 11) and Zusanli (ST 36) are used as the adjuvant acupoints. The twirling acupuncture technique is applied to achieve reinforcing or reducing. Four elements are determined to the successful application of this needling technique, i.e. direction of exertion, strength of exertion, manipulation duration of twirling needle, and the interval duration between two treatments of acupuncture. Eventually, the specification on acupuncture treatment for hypertension can be effectively promoted.

Neuromuscular Electric Stimulation in Addition to Exercise Therapy in Patients with Lower Extremity Paresis Due to Acute Ischemic Stroke. A proof-of-concept randomised controlled trial.

INTRODUCTION: Exercise therapy and neuromuscular electrical stimulation (NMES) during the initial 14 days after stroke may benefit recovery of gait. We aimed to determine whether poststroke NMES of vastus medial and tibial muscles during exercise therapy is more effective than exercise therapy alone. MATERIALS AND METHODS: In this proof-of-concept randomised trial patients with first-ever acute ischemic stroke and a leg paresis (40-85 years of age) were randomised (1:1) to 10 min of daily NMES + exercise therapy or exercise therapy alone. Primary outcome was the between-group difference in change in 6 min Walk Test (6MWT) at 90 days post stroke estimated with a mixed regression model. Secondary outcomes included 10 m Walk Test, Fugl-Meyer Motor Assessment, Guralnik Timed Standing Balance, Sit to Stand, Timed Up and Go, EQ-5D-5L, Montreal Cognitive Assessment and Becks Depression Inventory. RESULTS: 50 stroke survivors (25 in each group) with a mean age of 67 years (range 43-83) were included. An insignificant between-group difference in change of 28.3 m (95%CI -16.0 to 72.6, p = 0.23, adjusted for baseline) in 6MWT at 90-days follow-up was found, in favour of the NMES group. All secondary outcomes showed no statistically significant between-group difference. The conclusion was that adding NMES to exercise therapy had no effect on poststroke walking distance measured by the 6 MWT or any of the secondary outcomes. CONCLUSIONS: In this proof-of-concept RCT, we demonstrated that NMES in addition to exercise therapy during the first 14 days after onset of ischemic stroke did not improve walking distance or any of the secondary outcomes. Future studies with a longer trial period, stratifying patients into subgroups with comparable patterns of expected spontaneous recovery - if possible within 48 h post stroke, and greater sample size, than in this study are suggestions of how rehabilitation research could go on exploring the potential for NMES as an amplifier in stroke recovery.

Polyphenol Containing Sorghum Brans Exhibit an Anti-Cancer Effect in Apc Min/+ Mice Treated with Dextran Sodium Sulfate.

Colon cancer (CC) is considered a high-risk cancer in developed countries. Its etiology is correlated with a high consumption of red meat and low consumption of plant-based foods, including whole grains. Sorghum bran is rich in polyphenols. This study aimed to determine whether different high-phenolic sorghum brans suppress tumor formation in a genetic CC rodent model and elucidate mechanisms. Tissue culture experiments used colorectal cancer cell lines SW480, HCT-116 and Caco-2 and measured protein expression, and protein activity. The animal model used in this study was APC Min+/mouse model combined with dextram sodium sulfate. High phenolic sorghum bran extract treatment resulted in the inhibition of proliferation and induced apoptosis in CC cell lines. Treatment with high phenolic sorghum bran extracts repressed TNF-α-stimulated NF-κB transactivation and IGF-1-stimulated PI3K/AKT pathway via the downregulation of ß-catenin transactivation. Furthermore, high-phenolic sorghum bran extracts activated AMPK and autophagy. Feeding with high-phenolic sorghum bran for 6 weeks significantly suppressed tumor formation in an APC Min/+ dextran sodium sulfate promoted CC mouse model. Our data demonstrates the potential application of high-phenolic sorghum bran as a functional food for the prevention of CC.

Kinematic evaluation of patients with chronic obstructive pulmonary disease during the 6-min walk test.

BACKGROUND: A better understanding of gait kinematics during the 6-min walk test (6MWT) may facilitate the development of rehabilitation strategies for patients with chronic obstructive pulmonary disease (COPD). AIM: To evaluate gait kinematics during the 6MWT in patients with COPD. METHOD: Thirty-six patients with COPD and 19 healthy controls underwent a full-body kinematic analysis during the 6MWT. Data were collected using a system with four infrared cameras to capture the movement of a spherical marker covered with retroreflective tape attached to a helmet worn during the test. RESULTS: The walking distances measured by the assessor and by kinematics analysis were lower in the group of patients (P = 0.036 and P = 0.013, respectively). Moreover, the walking distances measured by kinematics analysis were greater than those measured by the assessor for both groups (P < 0.001). In the kinematics analysis of the complete test, the mean and maximum speeds were higher for the controls than for the patients (P = 0.007 and P = 0.044, respectively). In the half-turn analysis, acceleration, speed, and deceleration peaks (maximal absolute values) were lower for the patients than for the controls (P = 0.002, P = 0.012 and P = 0.006, respectively). CONCLUSIONS: Patients with COPD show worse functional capacity due to lower gait speed and acceleration-deceleration peaks after turnings as compared to healthy individuals during the 6MWT. Assessors can accurately predict the 6MWD measured by kinematics, though they underestimate this distance.