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While previous reports have established the anti-inflammatory effects of hangeshashinto, the intracellular signal transduction pathways involved have yet to be elucidated. We aim to employ an experimental system using oral cancer cells to assess the impact of hangeshashinto on intracellular signal transduction pathways in response to stimulation by Porphyromonas gingivalis pathogen-associated molecular patterns (PAMP). Hangeshashinto demonstrated the ability to inhibit the production of interleukin (IL)-6 and IL-8 induced by P. gingivalis PAMP. Furthermore, hangeshashinto suppressed the activation of the IL-6 promoter stimulated by PAMP. Hangeshashinto, like Toll-like receptor (TLR) signaling inhibitors (resatorvid and C29) and an immunosuppressant (dexamethasone), exhibited the ability to suppress TLR-mediated activation of the transcription factor nuclear factor-κB (NF-κB) in response to PAMP stimulation. This study suggests that the anti-inflammatory effects of hangeshashinto may be attributed to the inhibition of TLR signal transduction pathways including NF-κB activation, thereby suppressing NF-κB-dependent gene expression. [ABSTRACT FROM AUTHOR]

Background. Yin deficiency (YD) is a pathological condition characterized by emaciation, afternoon fever, dry mouth, and night sweats. The incidence of YD is 23.3%. A 27-item Yin Deficiency Scale (YDS) was developed to estimate the clinical severity of YD. This study aimed to develop three short-form YDS versions to reduce the burden of response time, using three item-reduction approaches: Rasch, equidiscriminatory item-total correlation (EITC), and factor-based analyses. Methods. Two datasets were analyzed from previous studies (169 outpatients from May to June 2009 and 237 healthy college students from January to April 2016). The optimal response category was examined using Rasch analysis. Items with higher item-total correlations were determined using the EITC. Using a factor-based approach, the items were reduced, while maintaining the original YDS construct. Reliability was estimated using the person separation index (PSI) and Cronbach's α values. The predictive accuracy was examined using the area under the curve (AUC). Finally, the relationship between YD and dysfunctional breathing (DB) was examined using factor scores from the YDS and the Korean version of the Nijmegen Questionnaire (KNQ). Results. We developed two 14-item YDS versions using the Rasch and EITC approaches, and a 16-item YDS version using a factor-based approach. Rasch analysis suggested an optimal response category of five points. The PSI of Rasch and Cronbach's α of the EITC and factor-based versions were 2.19, 0.855, and 0.827. The AUCs of the three short-form YDS were 0.812, 0.811, and 0.818. The sensitivity of the EITC-YDS was 0.632, which was lower than its specificity of 0.875. The fatigue-related scores of the factor-based YDS were fairly correlated with the factor scores of the KNQ estimating the DB (r = 0.349–0.499). Conclusion. The 14-item Rasch- and 16-item factor-based YDS may replace the original YDS during YD's primary screening, epidemiological surveys, and health checkups. [ABSTRACT FROM AUTHOR]

Introduction. Anethum graveolens (AG), commonly known as dill, is a plant from the Apiaceae family that has been traditionally used as a skin softener and purifying agent in Persian medicine. In a previous study conducted on male rats, dill was found to have anti-inflammatory effects. The current study aimed to examine the efficacy of topical application of Anethum graveolens oil on pruritus severity, skin dryness, sleep quality, and quality of life in patients undergoing hemodialysis. Methods. In the current clinical trial, the participants were randomly assigned to one of these groups: topical AG preparation, sesame oil, or a control group receiving no treatment. The study was double-blind and placebo-controlled. The topical treatment was applied twice a day for one month to areas of the skin affected by pruritus. The outcome measures included the severity of skin dryness, the Pittsburgh Sleep Quality Index, Duo's Uremic Pruritus Severity Scale, and the Itchy QoL questionnaire. Results. This study involved 106 hemodialysis patients, and after intervention for one month, the medication group had a significantly lower mean score of sleep quality (3.24 ± 2.41) than the placebo (4.54 ± 3.11) and control (5.05 ± 3.21) groups (P = 0.032). The mean change in pruritus severity was significantly greater in the medication group (−17.28 ± 8.938) than the placebo (−5.91 ± 5.398) and control (−3.43 ± 3.228) groups (P < 0.001). Moreover, a significant difference was observed in the mean changes in quality of life between the medication, placebo, and control groups, with values of −14.88 ± 7.89, −5.34 ± 4.50, and −1.92 ± 2.86, respectively (P < 0.001). Furthermore, both the medication and placebo groups showed improvement in skin dryness compared to the control group having the values of −1.65 ± 0.91, −1.11 ± 0.79, and −0.38 ± 0.54, respectively (P < 0.001). Conclusion. Topical Anethum graveolens preparation significantly improved the sleep quality and quality of life and reduced skin pruritus and dryness in hemodialysis patients. It could be considered as a simple therapeutic modality to control pruritus in hemodialysis patients. This trial is registered with IRCT2017022032671N1. [ABSTRACT FROM AUTHOR]

Existing research combines acupuncture theory with network science and proposes a new paradigm for the study of acupoint selection patterns—a key acupoint mining algorithm based on acupoint networks. However, the basic idea of this study for finding key acupoints is based on binary acupoint synergy relationships, which ignores the higher-order synergy among multiple acupoints and does not truly reflect the implicit patterns of each acupoint among meridian systems. Moreover, the mining results assessment method, which this new paradigm involves, does not have wide applicability and universality. In this paper, with the introduction of higher-order interactions between multiple acupoints, a high-specificity key acupoint mining algorithm based on 3-node motif is proposed in the acupoint-disease network (ADN). In response to the narrow applicability of the new research paradigm involving the evaluation of algorithms' measures, new and widely applicable and universal evaluation criteria are introduced in terms of resolution, network loss, and accuracy, respectively. Based on the principles of acupoint selection involved in acupuncture clinics in Chinese medicine, the acupoints involved in the data were divided into a total of 19 regions according to their distribution characteristics. From these 19 regions, we selected the key acupoints that have a large impact on the global network. Finally, we compared this algorithm with five other acupoint importance assessment algorithms in terms of resolution, network loss, and accuracy, respectively. The comprehensive results show that the algorithm identifies key acupoints with an accuracy of 63%, which is 14% to 21% higher than other existing methods. The key acupoints identified by the algorithm have a significant disruptive effect on the connectivity of the network, indicating that the key acupoints are at the core of the acupoint-disease network topology. They have a significant propagation influence on other acupoints, which means that the key acupoints have high-synergistic cooperation with other acupoints. Meanwhile, the stability and specificity of the algorithm ensure the reliability of the key acupoints. We believe that the key acupoints identified by the algorithm can be used as core acupoints from the perspective of network topology and high synergy of other acupoints, respectively, and help researchers explore targeted and high-impact combinations of acupoints to optimize existing acupuncture prescriptions under condition constraints. [ABSTRACT FROM AUTHOR]

Background. Podocarpus gracilis is an evergreen, dioecious tree found in Ethiopia and other African nations. It can reach a height of 60 meters. Without any scientific validation, ethnobotanical studies conducted in Ethiopia revealed that the Podocarpus gracilis plant's leaf is consumed orally to treat diabetes mellitus. Hence, this study aims to evaluate the in vivo blood glucose level lowering, lipid-lowering, and in vitro-free radical scavenging responses of Podocarpus gracilis leaf extract and fractions on experimental mice induced with diabetes. Methods. The in vitro antioxidant activity of PGC (Podocarpus gracilis) leaf extract was assessed by using a diphenyl-2-picrylhydrazyl (DPPH) assay. The oral glucose-loaded, normoglycemic, and streptozotocin- (STZ-) induced diabetic mouse models were employed. In the STZ-induced mice model, the leaf extract and solvent fractions activity on serum lipid and weight were also measured. The extract and fractions were tested at 100, 200, and 400 mg/kg dosages. One-way ANOVA was used to determine the statistical significance of BGL (blood glucose level) changes within and between groups, and Tukey's post hoc multiple comparisons were then performed. Results. In the acute toxicity study of Podocarpus gracilis leaf extract and fractions, there was no evidence of animal mortality at the maximum dose of 2 g/kg during the observation period. The extract-treated group with normoglycemia revealed a significant lowering in BGL at the 4-hour mark of 27.4% (p < 0.001) and 25.2% (p < 0.01) at doses of 200 mg/kg and 400 mg/kg, respectively, compared to that in negative control. In the oral glucose tolerance test (OGTT) model, only 400 mg/kg treated groups at 120 min after exposure showed a BGL reduction of 31.17% which was statistically significant (p < 0.05) in comparison to the negative control. In the single-dose STZ-induced model, eighth-hour BGL measurements from CE 100, CE 200, CE 400, and GLC5 showed drops in BGL of 43.1%, 44.1%, 45%, and 47.3% from baseline fasting BGL values. In the repeated streptozotocin (STZ)-induced model, at all doses of leaf extract and fractions, the fasting BGL was significantly (p < 0.001) reduced. Moreover, the leaf extract and solvent fractions have shown a significant (p < 0.001) reduction of serum lipids such as LDL, TC, and VLDL, and at the same time, it increases HDL at 14 days with body weight gained. In the test for antioxidant activity, the half-maximal inhibitory concentrations (IC50) for leaf extract and the standard medication (ascorbic acid) were 8.2 μg/ml and 3.3 μg/ml, respectively. The IC50 value denotes the concentration of the sample required to scavenge 50% DPPH radicals. Conclusion. The 80% hydromethanolic leaf extract and fractions of Podocarpus gracilis exhibited blood glucose lowering, lipid-lowering activity in normoglycemic, oral glucose tolerance test (OGTT) mode, and STZ-induced diabetic mice with weight gains. There is scientific support for the alleged traditional use as an antidiabetic, lipid-lowering, and antioxidant activity. The results need to be confirmed by future studies. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) pandemic occurred in Hong Kong for more than two years. This article conducted a cross-sectional study for participants to investigate the behavioral prevention, treatment, and rehabilitation of using Western medicines or herbal products for COVID-19 in Hong Kong. A questionnaire was designed and performed over 2 weeks from 1 May to 15 May 2022. It consisted of five parts with around 20 questions conducted including sociodemographic information, prevention, treatment, rehabilitation of COVID-19, and also the sources of information. The pattern usage of Chinese or Western medicines for COVID-19 was studied after data collection. 318 people participated in this survey, and only 311 were qualified. The sociodemographic information, e.g., personal educational level, and behavior for the prevention of COVID-19, which included wearing masks (98.7%), using alcohol hand sanitizer (83.0%), washing hands frequently (82.4%), avoiding crowds (53.1%), and staying home more often (50.6%). Western medicines, such as antipyretic drugs, antitussive drugs, and pain reliever drugs, whilst Chinese medicines, such as Lianhua Qingwen Jiaonang, Huoxiang Zhengqi San or Wan, and Nin Jiom Pei Pa Koa, were most commonly used in the treatment and rehabilitation periods of COVID-19. Herbal products, including lemon, honey, ginger, and herbal tea, were used as a daily diet to fight against COVID-19. Based on the result findings, Chinese medicines or herbal products were used during the COVID-19 pandemic, but most of the participants used an unknown Chinese medicine practitioner's prescription and self-administered Chinese medicine. The pattern of Chinese medicines and Western medicines' usage in the prevention, treatment, and rehabilitation of COVID-19 was also investigated; this showed a statistically significant association between the variables according to gender, age, and Chinese or Western medicines for further investigation. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the blood concentrations of quercetin in healthy participants after the administration of different formulations in single- and multiple-dose phases. Ten healthy adults (males, 5; females, 5; age 37 ± 11 years) participated in a diet-controlled, crossover pilot study. Participants received three different doses (250 mg, 500 mg, or 1000 mg) of quercetin aglycone orally. In the single-dose study, blood concentrations (AUC0–24 and Cmax) of standard quercetin were compared with those of LipoMicel®—a food-grade delivery form of quercetin. In the multiple-dose study, blood concentrations of formulated quercetin were observed over 72 h, after repeated doses of LipoMicel (LM) treatments. The AUC0–24 ranged from 77.3 to 1128.9 ng·h/ml: LM significantly increased blood concentrations of quercetin by 7-fold (LM 500) compared to standard quercetin, when tested at the same dose, over 24 h (p < 0.001); LM administered at a higher dose (LM 1000) achieved 15-fold higher absorption (p < 0.001); LM tested at half a dose of standard quercetin increased concentration by approx. 3-fold (LM 250). Quercetin blood concentrations were attained over 72 h. The major metabolites measured in the blood were methylated, sulfate, and glutathione (GSH) conjugates of quercetin. Significant differences in concentrations between quercetin conjugates (sulfate vs. methyl vs. GSH) were observed (p < 0.001). Data obtained from this study suggest that supplementation with LipoMicel® is a promising strategy to increase the absorption of quercetin and its health-promoting effects in humans. However, due to the low sample size in this pilot study, further research is still warranted to confirm the observations in larger populations. This trial is registered with NCT05611827. [ABSTRACT FROM AUTHOR]

Objective. Crataeva nurvala is a medicinal plant, which contains a wide range of polyphenolic and bioactive compounds. The aim of the study was to evaluate the renal-protective activity of Crataeva nurvala in two-kidney, one-clip (2K1C) rats. Methods. In this study, the ethanol extract of Crataeva nurvala bark at a dose of 100 mg/kg was orally used to treat 2K1C rats for four weeks. At the end of the experiment, all rats were sacrificed and tissue samples were collected for further biochemical and histological assessments. Results. This investigation showed that Crataeva nurvala treatment prevented the kidney dysfunction in 2K1C rats. Uric acid and creatinine concentration and CK-MB activities increased in 2K1C rats which were normalized by Crataeva nurvala. 2K1C rats also showed increased oxidative stress, depicted by the elevated level of MDA, NO, and APOP in plasma and tissues. Oxidative stress parameters declined in 2K1C rats by the treatment of Crataeva nurvala. These results could be attributed to the restoration of antioxidant enzyme activities such as catalase and SOD. Crataeva nurvala extracts also upregulated antioxidant gene expression in the kidneys of 2K1C rats. Moreover, several anti-inflammatory genes were suppressed by Crataeva nurvala treatment in 2K1C rats. Furthermore, fibrosis and collagen deposition in the kidneys were also lowered by the treatment of the Crataeva nurvala extract. Conclusion. The experimental data suggest that the Crataeva nurvala extract protected renal damage and oxidative stress, probably by restoring antioxidant enzymes activities in 2K1C rats. [ABSTRACT FROM AUTHOR]

Introduction. Abnormal uterine bleeding (AUB) is a major healthcare problem in females of reproductive age and impacts women's health and quality of life (QoL). This study aimed to test the equivalence of Persian Golnar (PG) and tranexamic acid (TA) for the treatment of excessive menstrual bleeding. Method. A triple-blind randomized equivalence trial with parallel design and block randomization technique was performed. A total of 80 patients with AUB were randomly allocated to receive either PG or TA for three consecutive menstrual cycles. Blood loss was measured by the Pictorial Blood Loss Assessment Chart (PBAC). Hematological evaluations were done before the intervention and after treatment. QoL and premenstrual dysphoric disorder (PMDD) as secondary outcomes were assessed using the menorrhagia questionnaire (MQ) and Premenstrual Symptoms Screening Tool (PSST). Statistical analysis was performed using an independent t-test, paired t-test, χ2 test, Mann–Whitney test, and Wilcoxon signed-rank test. Results. Seventy-six women completed the 12-week follow-up. Both PG and TA groups experienced a significant reduction in blood loss. Furthermore, the serum level of hemoglobin in the PG group enhanced significantly (P < 0.001). QoL and PMDD scores were significantly improved in both groups (P < 0.001). Conclusion. The findings of the current trial supposed that the Golnar product is as effective as tranexamic acid in controlling bleeding and enhancing the quality of life and premenstrual symptoms. [ABSTRACT FROM AUTHOR]

Among the many complications of type 2 diabetes (T2D), locomotor disorders have been poorly studied and understood. Therefore, no disease-modifying treatment is usually considered. The study aimed to investigate the effect of the aqueous extract of Sclerocarya birrea, Nauclea latifolia, and Piper longum (SNP) mixture on locomotor activity in fructose/streptozotocin-induced diabetic rats. T2D was induced by 10% fructose orally (6 weeks) and streptozotocin (STZ, 35 mg/kg, i.v.) in 25 male rats. Diabetic animals received distilled water, metformin (200 mg/kg), or the aqueous extract of the SNP mixture (75, 150, or 300 mg/kg). A 10-minute open field test was performed in diabetic rats (glycemia: 126 and 350 mg/dL) to assess locomotor activity before and after treatment. A group of 5 normal rats (NC) served as controls throughout the study. Rats were sacrificed, and the striatum was removed for biochemical and histological studies. In untreated diabetic rats, fructose/STZ administration resulted in hyperglycemia that altered locomotor function as characterized by increased freezing time, decreased mobility time, number of lines crossed, and total travel time compared to NC. MDA, TNF-α, INF-γ, and nitrite levels were elevated in the striatum of diabetic rats, while catalase activity and GSH levels were decreased, indicating oxidative stress and neuroinflammatory changes. In untreated diabetic rats, the microstructure of the HE-stained striatum revealed lipid vacuolation (hydropic degeneration) of the parenchyma, indicating a loss of neuronal integrity. The locomotor dysfunction was significantly improved by the aqueous extract of the SNP mixture, both biochemically and histologically. As a result, our findings support the mixture's ability to correct diabetes-related locomotion disorders as a glucose-lowering product and antioxidant, anti-inflammatory, and neuroprotective agent. These results justify the use of the aqueous extract of a combination of these three plants to manage diabetes and neuroinflammatory complications in Northern Cameroon. [ABSTRACT FROM AUTHOR]

Shudage-4, an ancient and well-known formula in traditional Mongolian medicine comprising four different types of traditional Chinese medicine, is widely used in the treatment of gastric ulcers. However, the potential material basis and molecular mechanism of Shudage-4 in attenuating stress-induced gastric ulcers remain unclear. This study aimed to first explore the potential material basis and molecular mechanism of Shudage-4 in attenuating gastric ulcers in rats. The chemical constituents and transitional components in the blood of Shudage-4 were identified by ultra-performance liquid chromatography time-of-flight mass spectrometry (UPLC-TOF-MS). The rat gastric ulcer model was induced by water immersion restraint stress (WIRS). The ulcer damage to gastric tissue was measured at the gross anatomical level and pathological level by hematoxylin-eosin (HE) staining of gastric tissue. RNA sequencing of gastric tissue and plasma metabolomics were performed to analyze the mechanism of Shudage-4 against gastric ulcers. A Pearson correlation analysis was performed to explore the association between serum metabolites and gene expression of gastric tissue. A total of 30 chemical constituents were identified in Shudage-4 by UPLC-TOF-MS. Among 30 constituents, 13 transitional components in the blood were considered as the potential material basis. Shudage-4 treatment had a significant effect on WIRS-induced gastric ulcers in rats. HE staining of gastric tissue illustrated that WIRS-induced ulcer damage was suppressed by Shudage-4 treatment. RNA sequencing of gastric tissue showed that 282 reversed expression genes in gastric tissue were related to Shudage-4 treatment, and gene set enrichment analysis revealed that Shudage-4 treatment significantly inhibited gene set expression related to reactive oxygen species (ROS), which was also validated by detecting rat gastric tissue MDA, GSH, SOD, GSH-Px, and CAT activities. The plasma metabolomic data demonstrated that 23 significantly differential metabolites were closely associated with the Shudage-4 treatment. The further multiomics joint analysis found that significantly upregulated 5 plasma metabolites in Shudage-4-treated rats compared to model rats were negatively correlated with gene set expression related to ROS in gastric tissue. Shudage-4 alleviated WIRS-induced gastric ulcers by inhibiting ROS generation, which was achieved by regulating plasma metabolites level. [ABSTRACT FROM AUTHOR]

Paclitaxel, one of the most effective chemotherapeutic drugs, is used to treat various cancers but it is exceedingly toxic when used long-term and can harm the liver. This study aimed to see if rutin, hesperidin, and their combination could protect male Wistar rats against paclitaxel (Taxol)-induced hepatotoxicity. Adult male Wistar rats were subdivided into 5 groups (each of six rats). The normal group was orally given the equivalent volume of vehicles for 6 weeks. The paclitaxel-administered control group received intraperitoneal injection of paclitaxel at a dose of 2 mg/Kg body weight twice a week for 6 weeks. Treated paclitaxel-administered groups were given paclitaxel similar to the paclitaxel-administered control group together with oral supplementation of rutin, hesperidin, and their combination at a dose of 10 mg/Kg body weight every other day for 6 weeks. The treatment of paclitaxel-administered rats with rutin and hesperidin significantly reduced paclitaxel-induced increases in serum alanine transaminase, aspartate transaminase, lactate dehydrogenase, alkaline phosphatase, and gamma-glutamyl transferase activities as well as total bilirubin level and liver lipid peroxidation. However, the levels of serum albumin, liver glutathione content, and the activities of liver superoxide dismutase and glutathione peroxidase increased. Furthermore, paclitaxel-induced harmful hepatic histological changes (central vein and portal area blood vessel congestion, fatty changes, and moderate necrotic changes with focal nuclear pyknosis, focal mononuclear infiltration, and Kupffer cell proliferation) were remarkably enhanced by rutin and hesperidin treatments. Moreover, the elevated hepatic proapoptotic mediator (caspase-3) and pro-inflammatory cytokine (tumor necrosis factor-α) expressions were decreased by the three treatments in paclitaxel-administered rats. The cotreatment with rutin and hesperidin was the most effective in restoring the majority of liver function and histological integrity. Therefore, rutin, hesperidin, and their combination may exert hepatic protective effects in paclitaxel-administered rats by improving antioxidant defenses and inhibiting inflammation and apoptosis. [ABSTRACT FROM AUTHOR]

Currently, antibiotic resistance is widespread among bacteria. This problem requires greater awareness because bacterial resistance increases, reducing antibiotic use effectiveness. Consequently, new alternative treatments are needed because the treatment options for these bacteria are limited. This work aims to determine the synergistic interaction and mechanism of action of Boesenbergia rotunda essential oil (BREO) against methicillin-resistant Staphylococcus aureus (MRSA). Gas chromatography-mass spectrometry identified 24 BREO chemicals (GC-MS). The main components of BREO were β-ocimene (36.73%), trans-geraniol (25.29%), camphor (14.98%), and eucalyptol (8.99%). BREO and CLX inhibited MRSA DMST 20649, 20651, and 20652 with a minimum inhibitory concentration (MIC) of 4 mg/mL and 512 µg/mL, respectively. The checkerboard method and the time-kill assay revealed synergy between BREO and CLX with fractional inhibitory concentration (FIC) <0.5 and log reduction >2log10 CFU/mL at 24 hours compared to the most effective chemical. BREO inhibited biofilm formation and increased membrane permeability. Exposure alone to BREO or in combination with CLX inhibited biofilm formation and increased cytoplasmic membrane (CM) permeability. The scanning electron microscopy (SEM) and transmission electron microscopy (TEM) results revealed that alterations in the cell walls, cytoplasmic membrane, and leakage of intracellular components of MRSA DMST 20651 after treatment with BREO alone and in combination with CLX were observed. These results indicate that BREO synergizes and could reverse the antibacterial activity of CLX against MRSA strains. The synergy of BREO may lead to novel drug combinations that increase the effectiveness of antibiotics against MRSA. [ABSTRACT FROM AUTHOR]

Menthofuran is a monoterpene present in various essential oils derived from species from Mentha genus, and in Brazil, those species are widely used in treating gastrointestinal and respiratory disorders. Considering the wide pharmacological potential of monoterpenes, including their antioxidant activity, this study aimed to evaluate menthofuran-gastroprotective activity, as well as the involvement of antioxidant mechanisms in this effect. The acute toxicity was evaluated according to the fixed dose method. The antiulcerogenic activity was investigated by using experimental models of gastric ulcers induced by ethanol, indomethacin, and ischemia/reperfusion in rats. The antisecretory gastric activity, the catalase activity, and the gastric wall mucus were determined in pylorus ligated rats. Gastric wall nonprotein sulfhydryl (NPSH) group content, myeloperoxidase (MPO) activity, and malondialdehyde (MDA) content were evaluated in ethanol-induced the gastric ulcer model. Menthofuran (2 g/kg) presented low acute toxicity and showed gastroprotective activity against ethanol-, indomethacin-, and ischemia/reperfusion-induced ulcers. Moreover, menthofuran presented antisecretory activity, reduced the total acidity, and increased pH of gastric secretion. On the other hand, a decrease in mucus content of gastric wall without alteration of gastric juice volume and catalase activity was observed. Interestingly, menthofuran increased NPSH levels and reduced MDA levels and MPO activity. Gastroprotective effects of menthofuran appear to be mediated, at least in part, by the NOS pathway, endogenous prostaglandins, reduced gastric juice acidity, increased concentration of the NPSH groups, and reduced lipidic peroxidation. These findings support the menthofuran as an effective gastroprotective agent, as well as the marked participation of antioxidant mechanisms in this response. [ABSTRACT FROM AUTHOR]

Objective. The sirtuin regulator 1-related enzyme (SIRT1) has been shown to play an important role in various pathophysiological processes. Our aim was to investigate the effect and correlation of serum SIRT1 combined with uterine hemodynamic parameters on disease severity and fetal uterine growth restriction in the progression of preeclampsia and to evaluate its clinical value as a potential marker. Methods. A total of 100 patients with preeclampsia who were hospitalized in Qufu Normal University Hospital from June 2017 to June 2021 were selected as the research objects. According to the severity, they were divided into the mild (62 cases) and severe groups (38 cases), and according to whether the fetal growth restriction was combined or not, they were divided into the combined fetal growth restriction group (56 cases) and the uncomplicated fetal growth restriction group (44 cases). Serum SIRT1 expression and uterine artery hemodynamic parameters were detected, and Spearman analysis was used to evaluate the association of serum SIRT1 expression and uterine artery hemodynamic parameters (the peak-to-trough ratio of arterial blood velocity, the pulsatility index, and the resistance index) with disease severity (systolic blood pressure, diastolic blood pressure, and random urinary protein levels) and fetal growth restriction (femoral length, biparietal diameter, head circumference, and neonatal weight); unsupervised principal component analysis (PCA), supervised partial least-squares discrimination analysis (PLS-DA), cluster heat map analysis, the receiver operating characteristic (ROC) curve, and the area under curve (AUC) were used to evaluate the diagnostic value of serum SIRT1 expression combined with uterine artery hemodynamic parameters in the severity of disease and fetal growth restriction in patients with preeclampsia. Results. Compared with patients with mild preeclampsia, serum SIRT1 expression was lower in patients with severe preeclampsia (p < 0.0001), the arterial blood flow velocity peak-to-trough ratio, pulsatility index, and resistance index were higher (p < 0.001 ; p < 0.0001); and serum SIRT1 expression and uterine artery hemodynamic parameters were closely related to disease severity (p < 0.001 ; p < 0.0001). In addition, the expression of serum SIRT1 in patients with preeclampsia combined with fetal growth restriction was lower than patients without preeclampsia (p < 0.0001); the peak-to-trough ratio of arterial blood flow velocity, the pulsatility index, and the resistance index were higher (p < 0.0001); and serum SIRT1 expression and uterine artery hemodynamics were closely related to fetal growth restriction (p < 0.0001). Unsupervised PCA analysis and supervised PLS-DA analysis showed that patients with different severity of disease and patients with or without fetal growth restriction were similar within the groups, and there were significant differences between the groups; cluster heat map analysis showed that the mild and severe groups were stratified clustering, and the combined fetal growth restriction group and the uncombined group were hierarchically clustered; ROC curve showed that the AUC of serum SIRT1 expression combined with uterine artery hemodynamic parameters was 0.776 in identifying the severity of preeclampsia and 0.956 in identifying the preeclampsia complicated by fetal growth restriction. Conclusion. Serum SIRT1 combined with uterine hemodynamic parameters in preeclampsia is closely related to disease severity and fetal growth restriction and is expected to become a potential biomarker for early clinical intervention in patients. [ABSTRACT FROM AUTHOR]

Microcystin-leucine-arginine (MCLR) is the most abundant cyanotoxin produced by cyanobacteria. It induces potent cytotoxicity through oxidative stress and DNA damage. Thymoquinone (TQ) is a natural nutraceutical antioxidant derived from black cumin (Nigella sativa). Physical exercise (EX) improves whole-body metabolic homeostasis. Therefore, this study examined the protective role of swimming exercise and TQ against MC-induced toxicity in mice. Fifty-six healthy adult male albino mice (25–30 g) were randomized into seven groups; group (I) was the negative control and received oral physiological saline for 21 days; group (II) received water EX for 30 min daily; group (III) was intraperitoneally injected with TQ (5 mg/kg daily, for 21 days); group (IV) was intraperitoneally administered MC (10 μg/kg daily, for 14 days) and acted as the positive toxic control; group (V) was treated with MC and water EX; group (VI) was injected with MC and TQ; finally, group (VII) was treated with MC with TQ and water EX. In comparison with the control group, the results showed hepatic, renal, and cardiac toxicity in the MCLR-treated group, indicated by a significant increase (p < 0.05) in serum levels of alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine transferase (ALT), cholesterol, lactate dehydrogenase (LDH), creatine kinase (CK), creatine kinase-myocardial band (CK-MB), urea, creatinine, interleukin-6, interleukin -1β, and tumor necrosis factor-α levels. In addition, there were significant elevations (p < 0.05) in malondialdehyde (MDA) and nitric oxide (NO) levels and a significant decrease in reduced glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) in hepatic, cardiac, and renal tissues. Treatment with either TQ or water EX significantly improved (p < 0.05) the MC-induced toxicity with superiority of the TQ group in the restoration of normal ranges; however, cotreatment with both TQ and swimming EX showed the most improvement and restoration to normal ranges as a result of increasing EX clinical efficacy by TQ. [ABSTRACT FROM AUTHOR]

Background. Drug resistance is currently possible anywhere in the world. Due to the discovery of antimicrobials, medicine, and health have made tremendous advances over the past several decades. Aim. This research evaluated the antimicrobial and cytotoxicity effects of green synthesis of copper oxide nanoparticles (CuO NPs) on Lactobacillus acidophilus and human embryonic kidney 293 cells (HEK). Method and Materials. Propolis was sampled and extracted. Green synthesis of CuO NPs was synthesized and characterized using SEM, TEM, DLS, BET, and zeta potential methods. L. acidophilus (ATCC 4356) was used, and the antimicrobial tests were carried out at different concentrations (10≥ mg/ml). Moreover, the cytotoxicity was evaluated using an MTT assay on human embryonic kidney 293 cells (HEK). Results. Synthesized CuO NPs using propolis extracts from Khalkhal (sample 1) and Gillan (sample 2) showed −13.2 and −14.4 mV, respectively. The hydrodynamic sizes of well-dispersed samples 1 and 2 were 3124.9 nm and 1726.7 nm, respectively. According to BET analysis, samples 1 and 2 had 5.37 and 8.45 m2/g surface area, respectively. The surface area was decreased due to the addition of propolis extract, and the pore size was increased. CuO NPs of samples 1 and 2 were visible on SEM images with diameters ranging from 75 to 145 nm and 120 to 155 nm, respectively. Based on TEM analysis, the size of CuO particles was increased in samples 1 and 2. CuO NPs particles had narrow size distributions with evenly dispersed NPs on all sides. The cell viability of the CuO NPs of samples 1 and 2 after 24, 48, and 72 hours was greater than 50%. As a result of the MIC and MBC tests, it was determined that samples 1 and 2 had the same effect against L. acidophilus (0.0024 mg/ml). Biofilm formation and degradation of sample 1 were more efficient against L. acidophilus. Conclusion. There was no evidence of cytotoxicity in the samples. In addition, results showed that the green synthesized CuO NPs from Khalkhal propolis were effective against L. acidophilus. Thus, the green synthesized CuO NPs from Khalkhal propolis were the best candidates for clinical application. [ABSTRACT FROM AUTHOR]

Background. Myocardial infarction (MI) is the most severe manifestation of cardiovascular disease. Xuefu Zhuyu Capsule (XFC), a proprietary Chinese medicine, is widely used in various cardiovascular diseases. At present, the molecular mechanism of XFC remains unclear. Objective. To explore the mechanism of anti-MI effects of XFC by combining network pharmacology and experiments. Methods. TCMSP, GeneCards, and DisGeNET databases were used to find the target of XFC. PPI analysis was performed by the STRING database. KEGG and GO analyses were performed by Metascape Database. Molecular docking was performed by Autodock Vina. HE staining, echocardiography, immunofluorescence, and TUNEL were performed to verify the prediction results. Results. Network pharmacology showed that quercetin, kaempferol, β-sitosterol, luteolin, and baicalein were the main active ingredients of XFC. TNF, IL6, TP53, VEGFA, JUN, CASP3, and SIRT1 were the main targets of XFC. KEGG results showed that key genes were mainly enriched in lipid and atherosclerosis, PI3K-Akt signaling pathway, MAPK signaling pathway, and NF-κB signaling pathway. HE staining showed that XFC could improve the morphology of myocardial tissue. Echocardiography showed that XFC could improve cardiac function. TUNEL showed that XFC could reduce cardiomyocyte apoptosis. Immunofluorescence showed that XFC could reduce the expression of α-smooth muscle actin (α-SMA) and increase the expression of CD31. In addition, we found that XFC may exert its therapeutic effects through SIRT1. Conclusion. This study demonstrated that SIRT1 may be the target of XFC in the treatment of MI. The active ingredients of XFC and SIRT1 can be stably bound. XFC could inhibit apoptosis, promote angiogenesis, and improve myocardial fibrosis through SIRT1. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy (DN) is one of the most severe microvascular complications of diabetes and has become the leading cause of end-stage renal disease formation. The pathogenesis of diabetic nephropathy is very complex and is still not fully understood. Fisetin is a flavonoid polyphenolic compound that is widely found in different fruits, vegetables, and medicinal plants. Many studies have indicated that it has a variety of pharmacological activities. In this study, we investigated the mechanism of action of fisetin in the protection of DN-induced podocyte injury both in vivo and in vitro. Results showed that fisetin could reduce high glucose (HG)-induced podocyte injury and streptozotocin (STZ)-induced diabetic nephropathy in mice. According to the histopathological staining results, fisetin ameliorated DN-induced glomerular injury in a dose-dependent manner. Western blot and immunofluorescence results showed that fisetin effectively promoted the expression of podocyte functional integrity marker proteins and inhibited the expression of podocyte injury marker proteins. In addition, according to the Western blot and RT-qPCR results, fisetin activates the nuclear translocation of Nrf2 to exert antioxidative stress ability and affects the expression of downstream antioxidant enzymes HO-1, GPX4, and other ferroptosis-related markers, thereby protecting against HG-induced podocyte ferroptosis and oxidative stress injury in DN mice. In summary, this study demonstrated that fisetin could enhance the antioxidative stress capacity of DN mice by promoting the activation of the Nrf2/HO-1/GPX4 signaling pathway in renal tissues, and attenuated HG-induced podocytes injury and STZ-induced DN in mice. [ABSTRACT FROM AUTHOR]

Objectives. The aim of the study is to evaluate the efficacy and prognosis of neoadjuvant chemotherapy (NAC) combined with breast-conserving surgery (BCS) in treating triple-negative breast cancer (TNBC) and analyze the influencing factors and predictors of the efficiency and prognosis of NAC. Methods. A retrospective cohort study was conducted by dividing patients into two groups according to two different therapy methods. With BCS as the exposure factor, 46 cases were assigned to the exposed group and 80 cases to the nonexposed group. We compare the difference in operation-related indicators, postoperative complications, local recurrence rate, distant metastasis rate, and overall survival (OS) rate between the two groups. The factors affecting the efficiency and prognosis of NAC were analyzed by binary logistic regression, and the optimal cutoff value was determined by the area under the ROC curve (AUC). The survival curve was plotted, and the univariate log-rank test was performed to analyze the difference in OS between the two groups. The influencing factors of OS were analyzed by the Cox risk regression model. Results. NAC + BCS resulted in significantly less intraoperative blood loss, lower incidence of postoperative complications, and shorter operative time and length of hospital stay than that in NAC (P < 0.05). There was no significant difference in local recurrence, distant metastasis, or OS between the two groups (P > 0.05). Multivariate analysis showed that the clinical stage I and Ki-67 high expression were independent protective factors of the efficacy of NAC. The high expression of Ki-67 and nondecline expression of Ki-67 were independent risk factors of prognosis. Ki-67 high expression was an independent risk factor of OS (P < 0.05). The ROC curve showed that the AUC of Ki-67 for NAC efficacy, prognosis, and OS were 0.706, 0.820, and 0.687, respectively, with optimal cutoff values of 25.5%, 29.0%, and 32.5%, respectively. Survival analysis showed that the OS of patients with NAC + BCS was 73.9% and NAC + MRM was 70.0% (P > 0.05). In the low expression subgroup of Ki-67, the OS of the two groups were 100.0% and 77.8%, respectively (P = 0.060). In the high expression subgroup of Ki-67, the OS of the two groups were 53.8% and 63.6%, respectively (P = 0.419). Conclusions. NAC + BCS is a good method for treating TNBC, which has an obvious short-term effect and a good long-term prognosis. Clinical stage I and the high expression of Ki-67 are independent protective factors for the efficacy of NAC. The high expression of Ki-67 and nondecline expression of Ki-67 are independent risk factors of prognosis. Ki-67 is a potential predictor for the efficacy, prognosis, and OS of NAC in TNBC patients. The high expression of Ki-67 indicates better NAC efficacy, a poorer prognosis, and a lower OS. [ABSTRACT FROM AUTHOR]

Background. The mortality of intensive care unit (ICU) patients ranges from 5% to 30%, and nucleated red blood cells (NRBCs) were revealed to be related to mortality. However, few studies have discussed the causes of NRBC or compared the dynamic count among patients with underlying diseases. Aim. To explore the possible causes of NRBC in ICU patients and the dynamic trends between survival and death groups and underlying disease subgroups. Methods. A total of 177 ICU patients were retrospectively included. The possible causes of NRBC in ICU patients were discussed. The relationship between NRBC and in-hospital mortality and the dynamic trend of NRBC during hospitalization between the survival and death groups and underlying disease subgroups were compared. Results. The Acute Physiology and Chronic Health Evaluation II (APACHE II) score and Sequential Organ Failure Assessment (SOFA) score in the NRBC-positive group were higher (23.52 ± 9.39 vs. 19.62 ± 7.59; 13.50 (9.00–17.50) vs. 8.00 (6.00–12.00)). Red blood cell count (RBC), hemoglobin (Hb) level, oxygen saturation (SO2), oxygenation index (OI), and serum protein level were lower in the NRBC-positive group. However, D-dimer (D-D), liver and kidney function indices, lactate dehydrogenase (LDH), C-reactive protein (CRP), and procalcitonin (PCT) were higher than those in the NRBC-negative group. Correlation analysis showed that NRBC count was positively correlated with alkaline phosphatase (ALP) and red blood cell distribution width (RDW) and negatively correlated with SO2 (r = 0.431, P < 0.05 ; r = 0.363, P < 0.05 ; r = −0.335, P < 0.05). The mortality rate in the NRBC-positive group was higher, and the median survival time was shorter than that in the NRBC-negative group (77.9% vs. 95.7%, P < 0.001 ; 15 days vs. 8.5 days, P < 0.01). Univariate and multivariate Cox regression analyses showed that NRBC was an independent risk factor for in-hospital mortality (HR: 1.12 (1.03–1.22), P < 0.01). The NRBC count had different hazard ratios (HRs) for in-hospital mortality in the subgroups. Locally weighted scatterplot smoothing (LOWESS) analysis revealed that the NRBC count in the death group was higher and had a sharp upward trend before death, whereas that in the survival group was negative or stayed at a low level. The changing trend of the NRBC count was different in patients with different underlying diseases. Conclusion. The possible cause of NRBC in ICU patients was related to inflammation and hypoxia. The persistently high level and rapid upward trend of NRBC counts are risk factors for in-hospital mortality in ICU patients. The changing trend of the NRBC count varied in patients with different underlying diseases. [ABSTRACT FROM AUTHOR]

Background. Danggui-Shaoyao-San (DSS) is a traditional Chinese medicine formula that has been widely used to treat a variety of disorders, including renal diseases. Despite being well-established in clinical practice, the mechanisms behind the therapeutic effects of DSS on diabetic nephropathy (DN) remain elusive. Methods. To explore the therapeutic mechanism, we explored the action mechanism of DSS on DN using network pharmacology strategies. All ingredients were selected from the relevant databases, and active ingredients were chosen on the basis of their oral bioavailability prediction and drug-likeness evaluation. The putative proteins of DSS were obtained from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, whereas the potential genes of DN were obtained from the GeneCards and OMIM databases. Enrichment analysis using gene ontology (GO) and the Kyoto encyclopedia of genes and genomes (KEGG) was performed to discover possible hub targets and gene-related pathways. Afterwards, the underlying molecular mechanisms of DSS against DN were validated experimentally in vivo against db/db mice. Results. We identified 91 phytochemicals using the comprehensive network pharmacology technique, 51 of which were chosen as bioactive components. There were 40 proteins and 20 pathways in the target-pathway network. The experimental validation results demonstrated that DSS may reduce the expression of TNF-α, IL-6, and ICAM-1, as well as extracellular matrix deposition, by blocking the JNK pathway activation, which protects against kidney injury. Conclusion. This study discovered the putative molecular mechanisms of action of DSS against diabetic kidney damage through a network pharmacology approach and experimental validation. [ABSTRACT FROM AUTHOR]

Asthma is a common pulmonary disease mainly caused by the infiltration of neutrophils. There is a limit to the therapeutic effects of the available asthma drugs on neutrophilic asthma. Shegan Mahuang Decoction (SMD) is one of the representative traditional Chinese medicine (TCM) prescriptions for asthma, and it can effectively relieve the clinical symptoms of patients. However, the effect of SMD on the treatment of neutrophilic asthma remains unknown. In this study, a mouse model of neutrophilic asthma induced by lipopolysaccharide (LPS)/ovalbumin (OVA) was established, and the effect of a modified SMD prescription on the model was evaluated. After treatment, SMD was demonstrated to be therapeutically effective on asthmatic mice via airway resistance detection and lung pathology and was able to affect cytokine levels in vivo. Further experiments verified that SMD regulated the expression of mitochondrial function proteins in bronchoalveolar lavage fluid (BALF) exosomes. The results demonstrate that SMD confers a therapeutic effect on a neutrophilic asthma mouse model, and it may reduce neutrophil airway inflammation by regulating myeloid-derived regulatory cell (MDRC) function and airway exosome mitochondrial function. [ABSTRACT FROM AUTHOR]

Cholangiocarcinoma (CCA) is a very aggressive tumor. The development of a new therapeutic drug for CCA is required. This study aims to evaluate the antitumor effect of ∆9-tetrahydrocannabinol (THC), the major psychoactive component of marijuana (Cannabis sativa), and cannabinol (CBN), a minor, low-psychoactive cannabinoid, on CCA cells and xenograft mice. THC and CBN were isolated, and their identities were confirmed by comparing 1H- and 13C-NMR spectra and mass spectra with a database. Cell proliferation, cell migration, and cell apoptosis assays were performed in HuCCT1 human CCA cells treated with THC or CBN. The phosphorylation of signaling molecules in HuCCT1 cells was detected. To determine the effects of THC and CBN in an animal model, HuCCT1 cells were inoculated subcutaneously into nude mice. After the tumors reached an appropriate size, the mice were treated with THC or CBN for 21 days. Tumor volumes were monitored and calculated. The 1H- and 13C-NMR data of THC and CBN were almost identical to those reported in the literature. THC and CBN significantly inhibited cell proliferation and migration and induced apoptosis in HuCCT1 cells. The phosphorylation of AKT, GSK-3α/β, and ERK1/2 decreased in HuCCT1 cells treated with THC or CBN. CCA xenograft mice treated with THC showed significantly slower tumor progression and smaller tumor volumes than control mice. THC and CBN induced apoptosis in CCA by inhibiting the AKT and MAPK pathways. These findings provide a strong rationale for THC and CBN as therapeutic options for CCA. [ABSTRACT FROM AUTHOR]

Gedan Jiangya Decoction (GJD), a Chinese herbal medicine composed of six botanical medicines, was designed to treat hypertension (patent published number (CN114246896A)). The overexpression of the ERK (extracellular signal-regulated kinase) signaling pathway is essential in developing left ventricular hypertrophy (LVH). This study aimed to evaluate GJD's effects on LVH in spontaneously hypertensive rats (SHRs) and examine its potential mechanisms on Ras/ERK1/2 pathway regulation. Thirty-five ten-week-old SHRs were randomly assigned to one of five groups: GJD low dosage, medium dose, high dose, model, and captopril. Wistar–Kyoto (WKY) rats served as the control group. All rats received a 6-week treatment. The following parameters were measured: systolic (SBP) and diastolic blood pressure (DBP), left ventricular mass index (LVMI), and serum TGF-beta1. The pathologic structure was determined by H & E staining and Masson. TGF-beta1, Ras, ERK1/2, and C-Fos levels were determined using western blotting and real-time qPCR. SBP, DBP, and LVMI were reduced significantly in the GJD group compared with the model group. GJD inhibited TGF-beta1, Ras, ERK1/2, and C-Fos expression in LVH. In conclusion, GJD reduced the Ras/ERK1/2 pathway expression, which decreased hypertension-induced heart hypertrophy. GJD may protect hypertension-induced myocardial hypertrophy by altering gene expression patterns in the heart. [ABSTRACT FROM AUTHOR]

Background. The use of herbal medicine is common in Ethiopia. However, evidence on the extent and predictors of concomitant use of herbal medicine with conventional treatment among HIV/AIDS and tuberculosis patients is limited. Objective. To assess the extent of concomitant use of herbal medicine with conventional therapy and associated factors among HIV/AIDS and tuberculosis patients in Metekel Zone, Northwest Ethiopia. Method. A cross-sectional study was conducted from January to March 2020. HIV/AIDS and tuberculosis patients who visited the health facilities during the study were interviewed face-to-face using a structured and pretested questionnaire. The descriptive statistics and univariate and multivariate logistic regression analyses were conducted using SPSS version 25. A P -value of <0.05 was considered significant. Results. 412 patients on conventional treatment were included in this study; 355 (86.2%) were HIV patients, and 57 (13.8%) were TB patients. More than half, 217 (52.7%) participants reported using herbal medicine while on conventional therapy. Among those who claimed to have used herbal medicines, 32 (14.7%) received herbal medicine from traditional healers. About four of five herbal users did not disclose their use to their healthcare providers. The type of health facility on follow-up (P = 0.03), disease status (P = 0.01), occupation (P = 0.02), discontinuing ART (P = 0.03), and encountering side (P = 0.04) were the determinant factors for the use of herbal medicine among our study participants. Conclusion. In the Metekel Zone, concomitant consumption of herbal medication is common among HIV/AIDS and tuberculosis patients. Furthermore, most patients did not disclose the healthcare practitioners about their herbal use. Therefore, healthcare practitioners must assess and counsel patients regarding the potential adverse effects and herb-drug interaction to optimize therapy. [ABSTRACT FROM AUTHOR]

Background. Malarial infection has significant negative impact on the health of the world population. It is treated by modern and traditional medicines. Among traditional medicinal plants, Acacia tortilis is used by different communities as antimalarial agent. Therefore, the objective of this study is to validate antimalarial activity of the stem bark of Acacia tortilis in mice. Methods. To evaluate antimalarial activity of the plant, 4-day suppressive, curative, and prophylactic antimalarial test models were used. Parasitemia, packed cell volume (PCV), survival time, rectal temperature, and body weight were used to evaluate the effect of the plant extracts. Data were analyzed using SPSS version 26 followed by Tukey's post hoc multiple comparison test. Results. The crude extract and dichloromethane fraction significantly suppressed the level of parasitemia (p < 0.001) and increased mean survival time (p < 0.01) at all tested doses. Similarly, significant effects were observed in mean survival time, % change of PCV, weight, and temperature in both curative and prophylactic antimalarial test models. Conclusions. The methanolic extract and solvent fractions of the stem bark of Acacia tortilis has shown antimalarial activity, and the finding supports the traditional use and the in vitro studies. Thus, this study can be used as an initiation for researchers to find the most active phytochemical entity and to conduct additional safety and efficacy tests. [ABSTRACT FROM AUTHOR]

Background. We aimed to develop a predictive difficult caudal epidural blockade (pDCEB) model when ultrasound was not available and verified the role of ultrasound in difficult caudal epidural blockade (CEB). Methods. From October 2018 to March 2019, this study consisted of three phases. First, we prospectively enrolled 202 patients scheduled to undergo caudal epidural anesthesia and assessed risk factors by binary logistic regression to develop the predictive scoring system. Second, we enrolled 87 patients to validate it. The receiver operating characteristic (ROC) curve was used to evaluate the performance of the prediction model. Youden-index was used to determine the cut-off value. Third, we enrolled 68 patients with a high risk of difficult CEB (pDCEB score ≥3) and randomized them into ultrasound and landmark groups to verify the role of ultrasound. Result. The rate of difficult CEB was 14.98% overall 289 patients. We found a correlation between unclear palpation of the sacral hiatus (OR 9.688) and cornua (OR 4.725), the number of the sacral hiatus by palpation ≥1 (OR 4.451), and history of difficult CEB (OR 39.282) with a higher possibility of difficult CEB. The area under the receiver operating characteristic curve of the pDCEB model involving the aforementioned factors was 0.889 (95% CI, 0.827–0.952) in the development cohort and 0.862 (95% CI, 0.747–0.977) in the validation cohort. For patients with a pDCEB score ≥3, a preprocedure ultrasound scan could reduce the incidence of difficult CEB (55.56% in the Landmark group vs. 9.38% in the ultrasound group, p < 0.001). Conclusion. This novel pDCEB score, which takes into account palpation of the sacral hiatus/cornua, number of the sacral hiatus by palpation ≥1, and history of difficult CEB, showed a good predictive ability of difficult CEB. The findings suggested that performing an ultrasound scan is essential for patients with a pDCEB score ≥3. Trial registration: No: ChiCTR1800018871, Site URL: https://www.chictr.org.cn/edit.aspx?pid=31875&htm=4; Principal investigator: Jialian Zhao, Date of registration: 2018.10.14. [ABSTRACT FROM AUTHOR]

Objectives. To investigate consistency between eye sign and nailfold video capillaroscopy (NVC) in systemic sclerosis (SSc) patients and to evaluate eye sign with various parameters of disease and potential pulmonary involvement. Methods. A total of 60 SSc patients and 20 healthy individuals were enrolled. 20 SSc patients were complicated with pulmonary arterial hypertension (PAH); 20 SSc patients with interstitial lung diseases (ILD); 20 SSc patients without pulmonary involvement. All subjects were assessed using the methods of NVC and eye sign. Skin involvement was evaluated by modified Rodnan skin score (mRSS) and disease activity according to Medsger's severity score (MSS). Clinical manifestations and the presence of autoantibodies were carefully recorded. Any correlations between were evaluated with the Spearman correlation coefficient test. Results. According to the morphological changes revealed by NVC, 3 types of NVC patterns have been characterized (early pattern, active pattern, and late pattern). Eye sign showed distinguishing morphologic changes in three patterns of NVC and pulmonary involvements (PAH vs ILD) in SSc. A positive linear correlation was found between scores of eye sign and NVC in all patients with SSc (r = 0.629, P = 0.001). A positive correlation of eye sign was found in all SSc patients with mRSS (r = 0.748, P = 0.045) and MSS (r = 0.636, P = 0.001). Conclusions. The study demonstrates that eye sign had a high consistency with NVC for the evaluation of the microcirculation in SSc patients and exhibited specific patterns in the early, active, and late phases of SSc. Eye sign can be used as a reliable method to classify and monitor SSc patients and replace the measurement of NVC. [ABSTRACT FROM AUTHOR]

Jambosa caryophyllus has been used in traditional phytotherapy as a treatment against infections. In the present work, essential oils extracted from clove buds (Jambosa caryophyllus) (EO-JC) were investigated for their composition, antifungal, and insecticidal properties. Extraction of EO-JC was performed by use of hydrodistillation using a Clevenger-type apparatus, and the EOs were analyzed by gas chromatography coupled with mass spectrometry (GC-MS). Antifungal activity of EO-JC was evaluated by the use of solid-state diffusion (disc method) and microdilution to determine the minimum inhibitory concentration (MIC), against three strains of fungus, Aspergillus niger, Aspergillus flavus, and Fusarium oxysporum. Insecticidal activity of EO-JC against the cowpea weevil, Callosobruchus maculatus, was determined to assess utility of EO-JC to control this pest. Several exposures including inhalation and contact were used to determine lethality, as well as the repulsion test was conducted at concentrations of 4, 8, 16, and 32 μL EO-JC. Characterization of EO-JC by GC/MS revealed 34 compounds accounting for 99.98% of the mass of the extract. The predominant compound was eugenol (26.80%) followed by β-caryophyllene (16.03%) and eugenyl acetate (5.83%). The antifungal activity of EO-JC on solid media exhibited inhibitions in the range of 49% to 87%, and MIC was between 3.125 and 7.80 μg EO-JC/mL. Insecticidal activity, as determined by the use of the inhalation test, and expressed as the LD50 and LD95 after 96 hours of exposure was 2.32 and 21.92 μL/L air, respectively. In the contact test, a 96-hour exposure resulted in LD50 and LD95 of 5.51 and 11.05 μL/L of air, respectively. EO-JC exhibited insecticidal activity against fungi and pest chickpea weevil. [ABSTRACT FROM AUTHOR]

Aims. This study aimsto investigate the relationship between peripheral blood neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), systemic immune-inflammatory index (SII), and procalcitonin (PCT), C-reactive protein (CRP), and pediatric critical illness score (PCIS) in infants with community-acquired pneumonia (CAP). Methods. 100 infants with bacterial CAP admitted to our hospital between January 2021 and December 2021 were selected as the infected group, and another 100 healthy infants who underwent health check-ups at the same time were selected as the control group, and the NLR, PLR, and SII of peripheral blood of infants in both groups and the serum PCT, CRP, and PCIS scores of infants in the infected group were tested. The correlation between NLR, PLR, SII, and PCT, CRP, and PCIS was analyzed by Spearman's analysis. Results. The peripheral blood levels of NLR, PLR, and SII were higher in the infected group than in the control infants (P < 0.05). The ROC results showed that the AUCs of peripheral blood NLR, PLR, and SII for the diagnosis of infants with CAP were 0.934, 0.737, and 0.882, respectively. The ROC results showed that the AUCs of peripheral blood NLR, PLR, and SII for assessing the extent of disease in infants with CAP were 0.815, 0.710, and 0.813, respectively, with best cut-off values of 2.05, 98.57, and 823.41; the joint predicted AUC was 0.862. Conclusions. NLR, PLR, and SII were significantly elevated in the peripheral blood of infants with CAP, positively correlated with PCT and CRP, and negatively correlated with PSIC scores, and NLR and SII also have some guiding value in early diagnosis and assessment of the extent of the disease in infants and toddlers with CAP. [ABSTRACT FROM AUTHOR]

Objective. To explore the clinical effect of acupoint application on the outcome of in vitro fertilization-embryo transfer (IVF-ET) in patients with polycystic ovary syndrome (PCOS) of the phlegm-dampness type and elucidate its possible mechanism of action from the perspective of follicular fluid metabolomics. Methods. A total of 90 patients undergoing IVF-ET due to infertility were selected and divided into three groups: the treatment group (PCOS with acupoint application, n = 30), the control group (PCOS without acupoint application, n = 30), and the normal group (non-PCOS, n = 30). All patients received a gonadotropin-releasing hormone agonist (GnRH-a) long protocol for controlled ovarian hyperstimulation (COH). Among them, the treatment group was also given the acupoint application from the day of pituitary downregulation to the day of the human chorionic gonadotrophin (hCG) trigger. Ultrahigh-performance liquid chromatography connected with quadrupole time-of-flight mass spectrometry (UHPLC-MS) was adopted for untargeted metabolomic analysis of follicular fluid collected from the three groups of patients on the day of oocyte pick-up (OPU). The significantly differential metabolites were screened using univariate and multivariate statistical analysis, and the related metabolic pathways were identified by the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Results. Metabolomic analysis showed that the treatment group's follicular fluid samples were aggregated with the normal group and separated from the control group. A total of 34 significantly differential metabolites were found in the follicular fluid of patients with phlegm-dampness PCOS and normal people. With the intervention of acupoint application, seven metabolites (pseudouridine, phenol, 2-oxoadipic acid, 9R,10S-EpOME, DL-lactate, nicotinamide, and DL-indole-3-lactic acid) were all downregulated, mainly involving the pathways of pyruvate metabolism, nicotinate and nicotinamide metabolism, protein digestion and absorption, biosynthesis of amino acids, and pyrimidine metabolism. Conclusions. Acupoint application can effectively improve the clinical symptoms and the outcome of IVF-ET treatment in patients with PCOS of the phlegm-dampness type, and its mechanism of action may be related to the regulation of the pathways of pyruvate metabolism, nicotinate and nicotinamide metabolism, protein digestion and absorption, biosynthesis of amino acids, and pyrimidine metabolism. [ABSTRACT FROM AUTHOR]

Objective. To identify simple and accurate pre-endoscopy risk factors for early identification of high-risk upper gastrointestinal bleeding. Methods. Patients who were admitted to Suzhou Hospital of Integrated Traditional Chinese and Western Medicine from January 1, 2016, to December 31, 2019, due to upper gastrointestinal bleeding were retrieved, and the detailed clinical data of the above patients were collected. Patients with a definite diagnosis of bleeding from esophageal/and gastric varices were assigned to the high-risk group. Patients with bleeding not caused by varices were divided into a high-risk and a low-risk group according to the Forrest grading and scoring standard (high-risk group Forrest Ia-IIb, low-risk group Forrest IIc-III). Univariate analysis, t-test, chi-square test, binary logistic regression, ROC curve (Receiver-operating characteristic curve), etc. were employed for analysis in order to identify some simple and accurate risk factors for high-risk upper digestion tract bleeding before endoscopy. Results. A total of 916 patients were collected. Three risk factors among the screened risk factors (1) hemoglobin ≤ 85 g/L, (2) vomiting red blood, and (3) "red bloody stool" were analyzed by ROC curve analysis. The specificities of each factor were 78.4%, 94.5%, and 96.7%, respectively, and the sensitivities were 71.8%, 55.9%, and 23.1%, respectively. We also derived a risk prediction scoring system for the three factors that meet the high risk such as (1) hemoglobin ≤ 83 g/L, (2)vomiting red blood, and (3) "red bloody stool." The area under the ROC curve (AUROC), sensitivity, and specificity were 0.877, 0.904, and 0.746. Conclusion. Hemoglobin ≤ 85 g/L, vomiting red blood, and red bloody stool were included in a simple scoring standard for predicting high-risk UGIB patients before endoscopy. The new risk prediction scoring system requires only three indicators and has the advantages of high accuracy, short time-consuming, and easy application. [ABSTRACT FROM AUTHOR]

Objective. Esophageal squamous-cell carcinoma (ESCC) is an aggressive malignant tumor, accounting for more than 90% of esophageal cancers. However, treatments such as surgical resection, radiotherapy, and chemotherapy are unable to achieve ideal clinical outcomes. The purpose of this study was to explore the effects of COQ10B on proliferation, apoptosis, migration, and invasion of esophageal squamous-cell carcinoma (ESCC) cells. Methods. Quantitative real-time PCR (qRT-PCR) was used to detect the expression of COQ10B in ESCC and normal tissues and in ESCC cell lines (KYSE-150 and TE-1). MTT assay and flow cytometry were applied to investigate the effects of COQ10B shRNA lentivirus (LV-shCOQ10B) on ESCC cell proliferation and apoptosis, respectively. The effect of COQ10B silencing on ESCC cell migration and invasion was determined by wound healing assay and transwell invasion assay, respectively. Results. The expression of COQ10B mRNA in ESCC tissues was higher than that in surrounding tissues. The decreased COQ10B level in KYSE-150 and TE-1 cells by LV-shCOQ10B could inhibit cell proliferation, promote cell apoptosis, and reduce the ability of invasion and migration (all P < 0.05). Conclusion. COQ10B was highly expressed in human ESCC tissues. COQ10B silencing contributed to the inhibition of proliferation, invasion, and migration of ESCC cells and the promotion of cell apoptosis, suggesting COQ10B may be a potential molecular target for the diagnosis and treatment of ESCC. [ABSTRACT FROM AUTHOR]

Background. Recurrent implantation failure (RIF), a clinical disorder characterized by failure to achieve pregnancy after repeated (≥3) embryo transfer, is a challenge for reproductive demands worldwide. In our preliminary work, the Zhuyun formula (ZYF) with auricular acupressure, a complementary and alternative medicine (CAM) with a small sample size for RIF, can improve the clinical pregnancy rate (41.2% vs. 26.7%, treatment group vs. control group, p < 0.05). Based on the toxicological and pregnancy-related pharmacological analysis of ZYF for RIF, the T-cell receptor signaling pathway might be involved in the pharmacological activity. This study aimed at evaluating the efficacy and safety of the CAM therapy according to pregnancy outcomes and maternal and child health and investigating the changes of T-helper (Th) cells in the peripheral blood of unexplained RIF women. Materials and Methods. We conducted a prospective, two-arms, randomized, nonblinded study. All eligible women were randomly assigned to the treatment group (TG) and the control group (CG) according to a computer-generated randomization list in sealed opaque envelopes. Blood samples were collected from the two groups, and serum Th1, Th2, and Treg were detected by flow cytometry. The cytokines were detected by an enzyme-linked immunosorbent assay (ELISA). The TG was administrated with ZYF and auricular acupressure for three months before ovarian stimulation, while the control group was on a waiting list for the same period. The primary outcome was CPR. The second outcomes were the serum levels of immune parameters. For the safety evaluation, the perinatal outcomes of maternal and child were obtained by follow-up. Post-hoc sensitivity analyses were performed to assess the effect of missing data. Results. One hundred and twenty-three women were randomized into the TG (n = 62) and CG (n = 61). The CPR was increased significantly in the TG (45.2%) than CG (26.2%) (p = 0.029). Twenty blood samples were collected, and the Th2/Th1 and Treg expression level was significantly higher in the TG than in the CG. IL-2, IL-10, and Foxp3 were higher significantly in the TG than in the CG. The maternal and child perinatal outcomes were not significantly different between the two groups. Conclusions. The ZYF with auricular acupressure was effective and safe in improving the pregnancy outcomes of RIF. It might be related to balancing the level of cytokines related to the immune tolerance of the maternal-fetal interface to protect the embryo from the maternal immune system. Clinical Trial Registration: Clinical Trial Registry; date: 14/Dec/2013; no. NCT03078205. [ABSTRACT FROM AUTHOR]

Glioma is the most commonly occurring primary neuroepithelial neoplasm. Long noncoding RNAs (lncRNAs) are emerging as pivotal modulators of gene expression in the immune system and play critical roles in the growth, progression, and immune response of carcinomas. In this study, we performed univariate Cox regression analysis on survival data from TCGA and identified 20 prognostic lncRNAs. Moreover, we revealed that these prognosis-related lncRNAs (PRLnc) were dysregulated in glioma. Furthermore, we constructed a signature based on the expression levels of these prognosis-related lncRNAs based on 13 prognostic lncRNAs, including AGAP2-AS1, CYTOR, MIR155HG, LINC00634, HOTAIRM1, SNHG18, LINC01841, LINC01842, LINC01426, MIR9-3HG, TMEM220-AS1, LINC00641, LINC01270, and LINC01503. The Kaplan–Meier curves show that high-risk patients had a shorter survival time. Finally, the glioma samples were classified into 2 subgroups based on the median expression of prognosis-related lncRNAs in each sample. In summary, these findings suggest that PRLnc is associated with tumor-infiltrating immune cells in glioma and that subtype 2 patients may respond more positively to immunotherapy. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a complex, age-related neurodegenerative disease that causes neuronal loss and dysfunction over time. An imbalance of redox potential of oxidative stress in the cell causes neurodegenerative diseases and dysfunction of neurons. Plants are a rich source of bioactive substances that attenuate oxidative stress in a variety of neurological disorders. The aim of the present study was to evaluate the Prunus armeniaca L. methanolic extract (PAME) for anti-Parkinson activity in rats. PD was induced with haloperidol (1 mg/kg, IP). The PAME was administered orally at 100, 300, and 800 mg/kg dose levels for 21 days. Behavioral studies (catalepsy test, hang test, open-field test, narrow beam walk, and hole-board test), oxidative stress biomarkers (SOD, CAT, GSH, and MDA) levels, neurotransmitters (dopamine, serotonin, and noradrenaline) levels, and acetylcholinesterase activity were quantified in the brain homogenate. Liver function tests (LFTs), renal function tests (RFTs), complete blood count (CBC), and lipid profiles were measured in the blood/serum samples to note the side effects of PAME at the selected doses. Histopathological analysis was performed on the brain (anti-PD study), liver, heart, and kidney (to check the toxicity of PAME on these vital organs). Motor functions were improved in the behavioral studies. Dopamine, serotonin, and noradrenaline levels were significantly increased (P < 0.001), whereas the level of acetylcholinesterase was decreased significantly (P < 0.001). The levels of superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH) were increased, while malondialdehyde (MDA) and nitrite levels were decreased in the PAME-treated groups significantly compared with the disease control group, hence reducing oxidative stress. The incidence of toxicity was determined by biochemical analysis of LFT and RFT biomarkers testing. The histopathological analysis indicated that neurofibrillary tangles and plaques decreased in a dose-dependent manner in the PAME-treated groups. Based on the data, it is concluded that PAME possessed good anti-Parkinson activity, rationalizing the plant's traditional use as a neuroprotective agent. [ABSTRACT FROM AUTHOR]

In this study, 383 differentially expressed genes (DEGs) between the allergic group and the nonallergic group were excavated. Humoral immune response, chemokine-related biological processes, granulocyte-related biological processes, IL-17 signaling pathway, and TNF signaling pathway were found connected with DEGs. The allergic group had significantly higher enrich scores of T cells, T helper cells, TFH, and Th17 cells than the nonallergic group. We acquired 26 rape pollen allergy-associated genes by taking the intersection of key module genes from WGCNA and the DEGs. The functional enrichment results show that rape pollen allergy-associated genes are relevant to processes and pathways like regulation of inflammatory response, transcriptional regulation, lymphocyte differentiation, IL-17 signaling pathway, and MAPK signaling pathway. Then, three characteristic genes were defined by crossing the genes derived from LASSO and SVM-RFE algorithms, including MYADM, PMAIP1, and MLF1. The AUC values of these genes manifested that the three genes had a mighty discrimination power in discriminating allergic samples from nonallergic samples. In conclusion, this study revealed three characteristic genes (MYADM, PMAIP1, and MLF1) in rape pollen allergy, suggesting that they may be potential biomarkers in rape pollen allergy diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Objective. To evaluate the effect of the VFQ-25 scale on the efficacy of Nd : YAG laser ablation in patients with different severity of vitreous opacities. Methods. From January 2020 to March 2021, data of patients who presented to our department and were diagnosed with vitreous opacity were collected, and the severity of vitreous opacity was divided into four grades: I, II, III, and IV. Preoperative visual acuity, intraocular pressure, dilated fundus, B ultrasound, and other examinations were performed, and the patients were scored using the VFQ-25 scale. All patients underwent Nd : YAG laser ablation and were followed for 6 months. The VFQ-25 scale was again used postoperatively to score the patient's efficacy. The general information and clinical characteristics of the patients we collected. The Spearman's test was used to evaluate the correlation between VFQ-25 score and Nd : YAG laser efficacy in patients. Results. A total of 80 patients (95 eyes) were included in this study. Vitreous opacities were grade I in 56 eyes (58.9%), grade II in 22 eyes (23.2%), grade III in 10 eyes (10.5%), and grade IV in 7 eyes (7.4%). Compared with preoperative scores, patients with vitreous opacity had significantly higher postoperative scores in terms of overall health (36.54 ± 17.06 vs 33.52 ± 16.74), overall visual acuity (60.39 ± 14.24 vs 57.56 ± 13.13), color vision (88.94 ± 12.56 vs 86.38 ± 12.37), and peripheral visual acuity (74.06 ± 18.38 vs 72.20 ± 18.79) items (all P < 0.001). The overall response rates of vitreous opacities I, II, III, and IV were 100%, 90.9%, 80.0%, and 71.4%, respectively. There was a significant correlation between the postoperative VFQ-25 total score, and the therapeutic effect of laser ablation for grade I vitreous opacities, with a correlation coefficient r of 0.417 (P = 0.001). The correlation coefficient r between the total score of postoperative VFQ-25 and the treatment effect of grade II vitreous opacity was 0.622 (P = 0.002). However, the correlation between the postoperative efficacy of grade III and IV patients and the VFQ-25 score was not significant. Conclusion. In patients with different degrees of vitreous opacity undergoing Nd : YAG laser vitreous ablation, the overall health, overall visual acuity, color vision, and peripheral visual acuity were improved after surgery, and the VFQ-25 score was significantly correlated with the postoperative efficacy, which is worthy of clinical use. [ABSTRACT FROM AUTHOR]

The development of resistance of microorganisms to conventional antibiotics is a major global health concern; hence, there is an increasing interest in medicinal plants as a therapeutic option. This study aimed to evaluate the antibacterial, anti-biofilm, and anti-quorum activities of crude extracts prepared using various solvents of nine indigenous South African plants used locally for the treatment of diarrhoea. The minimum inhibitory concentration (MIC) was determined using the broth microdilution method and the crystal violet assay was used to test the anti-biofilm activity of the extracts against a panel of bacteria. Anti-quorum sensing activity of the extracts was assessed via inhibition of violacein production in Chromobacterium violaceum ATCC 12472. Preliminary screening of extracts against E. coli ATCC 25922 revealed that the acetone extracts had significant activity, with MIC values ranging from 0.04 to 0.63 mg/mL. Further screening against a panel of bacterial pathogens showed that the acetone extract of Bauhinia bowkeri was the most active with MIC of 0.01 mg/mL against Salmonella enteritidis, followed by Searsia lancea with MIC of 0.03 mg/mL against Bacillus cereus. All the plant extracts prevented the attachment of biofilms by more than 50% against at least one of the tested bacteria. However, only the mature biofilm of B. cereus was susceptible to the extracts, with 98.22% eradication by Searsia pendulina extract. The minimum quorum sensing inhibitory concentration of the extracts ranged from 0.08 to 0.32 mg/mL with S. lancea having the most significant activity. The extract of S. lancea had the best violacein production inhibitory activity with IC50 value of 0.17 mg/mL. Overall, the results obtained indicate that acetone extracts of S. leptodictya, S. lancea, S. batophylla, S. pendulina, B. galpinii, and B. bowkeri possess antibacterial and anti-biofilm activities and can modulate quorum sensing through the inhibition of violacein production. Therefore, these results signify the potential of the selected plant extracts in treating diarrhoea through inhibition of bacterial growth, biofilm formation inhibition, and quorum sensing antagonism, supporting their medicinal use. [ABSTRACT FROM AUTHOR]

Objective. To explore the clinical curative effects of uterine arterial chemoembolization (UACE) combined with uterine curettage treating with cesarean scar pregnancy (CSP) patients, and analyze the influencing factors of postoperative efficacy. Methods. A total of 86 patients with CSP from January 2019 to December 2021 in the Gynecology ward of our hospital were selected and divided into the control group (n = 43) and the observation group (n = 43) according to the random number method. The control group was treated with an injection of methotrexate (MTX) combined with uterine curettage, and the observation group was treated with UACE combined with uterine curettage. Two months after the operation, the therapeutic effect, cesarean scar mass, and β-human chorionic gonadotropin (β-HCG) level were observed and compared between the two groups. The general conditions of patients in two groups were recorded, and the influencing factors of surgical efficacy in patients were analyzed using univariate analysis and a multivariate logistic regression model. Results. After treatment, the total effective rate of the observation group was significantly higher than that of the control group (P < 0.05). The volume of intraoperative blood loss, hospitalization period, menstrual recovery time, mass disappearance time, and β-HCG recovery time of the observation group were lower than those of the control group (P < 0.05). Single factor analysis showed that the number of cesarean sections, gestational age, the largest diameter of the gestational sac, the thinnest muscular layer, and the type of CSP can all affect postoperative efficacy (P < 0.05). Multivariate logistic analysis showed that the gestational age, a maximum diameter of a gestational sac, the thinnest muscular layer, and the type of CSP were independent factors influencing the postoperative efficacy of the patients (P < 0.05). Conclusion. UACE combined with uterine curettage for CSP can significantly improve the curative effect, reduce intraoperative bleeding, and improve the recovery time of postoperative-related symptoms. The gestational age of the patient, the maximum diameter of the gestational sac, the thinnest muscular layer, and the type of CSP can independently affect the therapeutic effect of CSP patients. Fully understanding the high-risk factors that affect the efficacy of treatment of CSP, timely preventive measures, and targeted care can effectively improve the prognosis and reduce the risk of CSP. [ABSTRACT FROM AUTHOR]

Background. Epidermal growth factor receptor inhibitors (EGFRIs) and tyrosine kinase inhibitors (TKIs) are key drugs in targeted cancer therapy. However, they may cause skin toxicity. We previously prepared a modified Huang-Lian-Jie-Du (mHLJD) decoction cream using 10 herbs, which effectively alleviated EGFRI/TKI-induced skin toxicity. In the present study, we identified the reference markers of the mHLJD decoction and investigated the anti-inflammatory and antibacterial effects of the mHLJD decoction extract. Methods. We performed high-performance liquid chromatography (HPLC) to determine the composition of the mHLJD decoction. Human epidermoid A431 cells were treated with tumor necrosis factor (TNF)-α to induce inflammation; then, the effects of the mHLJD decoction extract on the cytokine expression were determined using a cytokine array and by performing real-time quantitative polymerase chain reaction (qPCR). The antibacterial effects of the extract were examined using disk diffusion and microdilution assays. Results. HPLC results revealed that the mHLJD decoction primarily consisted of geniposide, berberine chloride, baicalin, coptisine, and palmatine. TNF-α treatment increased the expression of certain cytokines, including IL-1β, IL-8, M-CSF, and TGF-β2; however, pretreatment with the mHLJD decoction extract reduced their expression. The qPCR results demonstrated a decreased mRNA expression of IL-8, M-CSF, and TGF-β2. The antibacterial assay revealed that the extract exerted inhibitory effects on Staphylococcus aureus, forming an inhibition zone at the minimum inhibitory concentrations of 3.125 and 6.25 mg/mL; however, the extract exerted no effects on Escherichia coli and Pseudomonas aeruginosa. Conclusions. We developed an HPLC method to quantify the reference markers of the mHLJD decoction. The bioactivity analysis provided the potential mechanisms underlying the effects of the mHLJD decoction on EGFRI/TKI-induced skin toxicity. [ABSTRACT FROM AUTHOR]

Objective. To investigate the predictive value of thromboelastography for the occurrence of early neurological deterioration (END) in patients with primary acute cerebral infarction (ACI). Methods. 150 patients who were hospitalized in the department of neurology of our hospital from September 2020 to September 2021 and were clearly diagnosed with primary ACI by head CT and head magnetic resonance imaging (MRI) were selected and divided into END and non-END groups according to the change in National Institute of Health Stroke Scale (NIHSS) score within 72 h of admission. The general baseline data and laboratory indexes of the first examination at admission were compared between the two groups, and the factors that may affect the occurrence of END were determined by univariate analysis and multivariate logistic regression analysis, and the predictive value of thromboelastography on the occurrence of END after ACI was analyzed by applying the receiver operating characteristic (ROC) curve. Results. Time to onset, baseline NIHSS score, percentage of diabetes, white blood cell (WBC) levels, C-reactive protein (CRP), and apolipoprotein B (Apo B) levels were higher in the END group than in the non-END group (P < 0.05); coagulation reaction time (RT) (3.97 ± 1.16 vs. 5.49 ± 1.03) and kinetic time (KT) (1.32 ± 0.67 vs. 1.82 ± 0.58) were lower in the END group than in the non-END group (P < 0.05). Inthe END group (P < 0.05) diabetes, baseline NHISS score, CRP level, Apo B level, and RT were independent risk factors for the development of END in patients with ACI (P < 0.05). The AUC of RT to predict the occurrence of END in patients with ACI was 0.855 (95% CI: 0784 to 0925, P = 0.001), with a sensitivity of 81.70% and specificity of 78.00% when the optimal cut-off value was 0.597. Conclusion. NIHSS score at admission, CRP, apolipoprotein B, RT shortening, and diabetes mellitus were independent risk factors for the development of END in ACI patients; RT shortening in TEG was predictive of END in ACI patients. [ABSTRACT FROM AUTHOR]

Purpose. To assess the association between intestinal venous blood (IVB) circulating tumor cells (CTCs) and clinicopathological parameters in stage I-III colorectal cancer (CRC) patients. Methods. Participants were retrospectively retrieved, who were admitted to our hospital or took annual physical exams between December 1, 2015 and December 31, 2018. A negative enrichment-immunofluorescence in situ hybridization (NE-imFISH) technique was used to isolate and identify CTCs. Receiver operating characteristic (ROC) curves and Youden index values were used to determine the critical CTC cutoff value for the diagnosis of CRC. Kaplan-Meier and log-rank methods were used to conduct survival analyses, and multivariate Cox regression analyses were employed for multivariate corrections to comprehensively evaluate the value of CTCs in the diagnosis of CRC. Relationships between IVB CTCs, clinicopathological parameters, and prognosis were then analyzed based upon patient postoperative follow-up data. Results. In total, we retrieved 282 patients including 48 healthy controls, 72 patients with benign colorectal tumors, and 162 CRC patients. CRC patients exhibited significantly higher numbers of CTCs relative to control patients or those with benign disease. CTC numbers in CRC patient peripheral blood (PB) and IVB were closely associated with tumor node metastasis (TNM) staging (P < 0.01), carbohydrate antigen-125 (CA-125) levels (P < 0.001), and KRAS (Kirsten rat sarcoma virus oncogene) mutation status (P < 0.001). The disease-free survival (DFS) of patients in the CTC-negative group was significantly longer than that of patients in the CTC-positive group (24.60 ± 13.31 months vs. 18.70 ± 10.19 months, P < 0.05), with the same being true with respect to their overall survival (OS) (30.60 ± 12.44 months vs. 35.25 ± 11.57 months, P < 0.05). A multivariate analysis revealed that the detection ≥2 CTCs/3.2 ml was independently associated with poorer DFS and OS. CTC counts were independently predictive of CRC patients TNM staging, CA-125, and KRAS mutation status in both univariate and multivariate Cox proportional hazards regression analyses. Conclusion. CTCs are valuable biomarkers that can be monitored to predict CRC patient disease progression. [ABSTRACT FROM AUTHOR]

Background. Dysregulation of DnaJ heat shock protein family (HSP40) member C12 (DNAJC12) is implicated in the malignancy progression of multiple cancers. The current study aimed to determine the biology function and mechanism of DNAJC12 in rectal cancer (RC). Methods. RC tissues, adjacent tissues, RC cell lines, and normal colorectal epithelial cell lines were collected to analyze DNAJC12 expression. The abilities of DNAJC12 on proliferation, migration, and apoptosis of RC cells were detected by CCK-8, wound healing, and flow cytometry assays. Co-IP assays were carried out to confirm the association between DNAJC12 and HSPA4. The effect of DNAJC12 on tumor growth was detected by using the xenograft model of nude mice. Results. Elevation of DNAJC12 was uncovered in RC tissues and cell lines. DNAJC12 upregulation facilitated RC cell proliferation and migration and induced apoptosis, while DNAJC12 interference showed the opposite results. Besides, HSAP4 served as a potential binding protein for DNAJC12. Rescue experiments revealed that elevated of HSAP4 restored the impact of DNAJC12 silencing on the cell functions. Finally, DNAJC12 silencing hampered tumor growth of RC in vivo. Conclusion. In summary, this study highlighted a key player of DNAJC12 in modulating the malignant biological progression of RC via DNAJC12/HSPA4 axis, displaying a potential therapeutic target for RC. [ABSTRACT FROM AUTHOR]

Objective. Traditional Chinese medicine (TCM) emphasizes treatment based on syndrome differentiation. This study aimed to clarify the characteristics of DNA methylation expression profiles in peripheral blood mononuclear cells (PBMCs) in patients with psoriasis and analyze the differences in these profiles among different TCM syndromes of psoriasis in order to provide a material basis for the diversity of these syndromes. Methods. Blood samples were collected from 32 participants, including 14 patients with psoriatic blood heat syndrome (BHS), 12 patients with psoriatic blood stasis syndrome (BSS), and 6 healthy controls. PBMCs were extracted and subjected to DNA quality inspection. An Illumina Human Methylation 850k chip was used to sequence each group of samples. According to gene annotation classification together with CpG island annotation classification, the differentially methylated regions between sample groups were screened, while Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were applied to perform functional analyses of DMGs. Finally, the DMGs closely correlating with psoriatic severity were screened using Spearman's correlation analysis. Results. Compared with normal controls, patients with psoriasis showed an overall trend of hypermethylation. In psoriasis, the differential methylation probes were mainly distributed on gene body region on the genome, while those in CpG regions were mainly distributed in CpG islands. Compared with healthy controls, the overall trends in methylation were similar in psoriatic BHS and BSS patients compared to healthy controls. However, bioinformatic analysis revealed different functions of DMGs. We also found that the methylation levels of TRIM14 and PRDM16 were closely correlated with PASI scores and could serve as potential biomarkers to assess the severity of psoriasis. Conclusions. Our study, for the first time, indicated the possible involvement of DNA methylation in regulating the characteristics of TCM syndromes of psoriasis, providing a new direction for research into TCM psoriatic syndromes. [ABSTRACT FROM AUTHOR]

Cystic echinococcosis is a zoonotic disease caused by the parasite Echinococcus granulosus sensu lato (s.l.), which is worldwide distributed and causes long-lasting infections in animals and humans. The existing treatment is limited to the use of benzimidazoles, mainly albendazole (ABZ). However, it has unwanted side effects and its efficacy is about 50%. The Asteraceae family includes plants that have therapeutic applications (medicinal species) and has an important role in new drug development. The species belonging to a different genus of this family show a wide range of anti-inflammatory, antimicrobial, antioxidant, hepatoprotective, and antiparasitic activities, among others. The aim of the present study was to evaluate the in vitro efficacy of extracts of four Asteraceae species against protoscoleces of E. granulosus sensu stricto (s.s.). On the other hand, the Stevia aristata extract was assessed on the murine cyst of E. granulosus (s.s.) and the efficacy of S. aristata extract was investigated in a murine model of CE. Stevia satureiifolia, S. aristata, Grindelia pulchella, and G. chiloensis extracts at 100 μg/mL caused a decrease in protoscoleces viability; however, S. aristata extract produced the greatest in vitro protoscolicidal effect. After 20 days of treatment with the highest concentration (100 μg/mL) of S. aristata extract, protoscoleces viability decreased to 0%. The tegumental changes observed by scanning electron microscopy were consistent with the reduction in vitality. The collapse of the germinal layer was registered in 60 ± 5.8% and 83.3 ± 12.0% of cysts treated during 4 days with 50 and 100 μg/ml, respectively. The half maximal effective concentration (EC50) value of the S. aristata extract against E. granulosus (s.s.) cysts was 47.86 μg/mL (96 h). The dosage of infected animals with the 50 mg kg−1 dose of S. aristata extract resulted in a significant reduction in cyst weight in comparison with the control group. In conclusion, S. aristata extract was demonstrated to exert a marked effect, both in vitro and in the murine model. [ABSTRACT FROM AUTHOR]

Background. This study aimed to investigate the molecular mechanism of Tongfengding capsule (TFDC) in treating immune-inflammatory diseases of gouty arthritis (GA) and interleukin-1-beta (IL-1β) inhibitors by using network pharmacology, molecular docking, and cell experiments. Methods. In this study, the compounds of TFDC and the potential inflammatory targets of GA were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Online Mendelian Inheritance in Man (OMIM), and GeneCards databases. The TFDC-GA-potential targets interaction network was accomplished by the STRING database. The TFDC-active compound-potential target-GA network was constructed using Cytoscape software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were used to further explore the GA mechanism and therapeutic effects of TFDC. Quantitative real-time PCR (qPCR) was used to verify whether the TFDC inhibited IL-1β in GA. Molecular docking technology was used to analyze the optimal effective compounds from the TFDC for docking with IL-1β. Result. 133 active compounds and 242 targets were screened from the TFDC, and 25 of the targets intersected with GA inflammatory targets, which were considered as potential therapeutic targets. Network pharmacological analysis showed that the TFDC active compounds such as quercetin, stigmasterol, betavulgarin, rutaecarpine, naringenin, dihydrochelerythrine, and dihydrosanguinarine had better correlation with GA inflammatory targets such as PTGS2, PTGS1, NOS2, SLC6A3, HTR3A, PPARG, MAPK14, RELA, MMP9, and MMP2. The immune-inflammatory signaling pathways of the active compounds for treating GA are IL-17 signaling pathway, TNF signaling pathway, NOD-like receptor signaling pathway, NF-kappa B signaling pathway, Toll-like receptor signaling pathway, HIF-1 signaling pathway, etc. The TFDC reduced IL-1β mRNA expression in GA by qPCR. Molecular docking results suggested that rutaecarpine was the most appropriate natural IL-1β inhibitor. Conclusion. Our findings provide an essential role and bases for further immune-inflammatory studies on the molecular mechanisms of TFDC and IL-1β inhibitors development in GA. [ABSTRACT FROM AUTHOR]

Purpose. Analysis of routine biochemical levels of cerebrospinal fluid (CSF), distribution of pathogenic bacteria, and risk factors in patients with intracranial infections secondary to brain tumour surgery. Methods. A total of 208 patients admitted to our hospital for brain tumour surgery from January 2020 to May 2022 were selected. Fully automated biochemical analyzer was employed for CSF routine and for measuring biochemical parameters such as white blood cell (WBC), micrototal protein (M-TP), glucose (GLU), and chlorine (CI). Double antibody sandwich assay for CSF procalcitonin (PCT), heparin-binding protein (HBP), and matrix metalloproteinase-9 (MMP-9) was performed. Fully automated microbiological analyzer for pathogen identification was utilized. Based on the above results, we determined whether the patients had secondary intracranial infections after surgery and analyzed the risk factors for secondary intracranial infections after brain tumour surgery by univariate and multifactorial logistic regression. Results. Among 208 patients with brain tumour surgery, 65 cases (31.25%) had secondary intracranial infection and 143 cases (68.75%) had no secondary intracranial infection. The levels of WBC, M-TP, CI, PCT, HBP, and MMP-9 in the CSF of intracranially infected patients were significantly higher than those of uninfected patients (P < 0.05), and GLU was significantly lower than that of uninfected patients (P < 0.05), and the levels of PCT, HBP, and MMP-9 in infected patients were significantly lower than those before treatment after 3, 7, and 10 d and tended to decrease over time (P < 0.05). A total of 62 pathogenic strains were isolated from 65 intracranial infections, of which 41 (66.13%) were Gram-negative bacteria, mainly resistant to amikacin and ciprofloxacin and sensitive to meropenem and imipenem; 19 (30.65%) were Gram-positive bacteria, mainly highly resistant to penicillin and erythromycin and sensitive to vancomycin. Univariate analysis showed that age, gender, tumour type, history of glucocorticoid application, and prophylactic application of antibiotics were not associated with secondary intracranial infection after brain tumour surgery (P > 0.05); tumour site, operation time, postoperative indwelling drainage time, postoperative cerebrospinal fluid leakage, and history of diabetics were all associated with secondary intracranial infection after brain tumour surgery (P < 0.05). Multivariate logistic regression analysis showed that infratentorial tumour, operation time ≥4 h, postoperative indwelling drainage time ≥24 h, and postoperative cerebrospinal fluid leakage were independent risk factors for secondary intracranial infection after brain tumour surgery (P < 0.05). Conclusion. Patients with intracranial infections secondary to brain tumour surgery have abnormal levels of CSF routine and biochemical parameters, and the detection rate of Gram-negative bacteria is higher than that of Gram-positive bacteria in patients. Treatment should be based on the characteristics of pathogenic bacteria and risk factors with targeted interventions to reduce intracranial infections. [ABSTRACT FROM AUTHOR]

Objective. The aim of the study is to analyze the clinical characteristics of patients with H-type hypertension complicated with other chronic diseases in a community in Beijing and to explore the influencing factors related to the occurrence of the disease by means of a case-control study. Methods. A questionnaire was designed. 362 residents with H-type hypertension in a community in Beijing were randomly enrolled from January 2020 to December 2021. The general data and clinical indexes of the patients were collected and their clinical characteristics were analyzed. According to the complications of other chronic diseases, they were divided into the simple hypertension group (n = 65) and the other chronic disease group (n = 297). Univariate and multivariate analyses were used to analyze the influencing factors for H-type hypertension patients with other chronic diseases. Results. Among the 362 H-type hypertension patients, 21 cases were aged 35–45 years, 35 cases were aged 45–55 years, and 127 cases were aged 55–65 years. The number of patients aged ≥65 years was 179, and the number of patients aged ≥55 years accounted for the highest proportion with a constituent ratio of 85.00%. Only 65 patients were patients with simple hypertension. The remaining 297 patients were complicated with different kinds of chronic diseases. The types of chronic diseases include malignant tumors, diabetes, rheumatoid arthritis, coronary heart disease, asthma, chronic obstructive pulmonary disease, systemic lupus erythematosus, and stroke. The proportion of H-type hypertension complicated with coronary heart disease, diabetes, and stroke is higher. Among the 297 patients, most of them were local, resident, and nonagricultural patients with a constituent ratio of 89.90%, 95.96%, and 98.98%, respectively. The prevalence rate of the male was 59.60% higher than that of the female at 40.40%. The blood types B and AB were more common. 90.57% of patients were married and the proportion of body mass index (BMI) was 45.79%. 60.61% of patients had a history of smoking, 55.56% had a history of drinking, 35.02% had a regular physical examination, 14.81% had regular exercise, and 37.71% had a light diet. There were significant differences in marital status, smoking, alcohol consumption, regular exercise, and light diet between the simple hypertension group and the chronic disease group (P < 0.05). The results of the logistic regression analysis showed that smoking, drinking, little exercise, and not eating lightly were the independent risk factors for other chronic diseases (P < 0.05). Conclusion. The incidence of H-type hypertension is higher in people ≥55 years old. Most of them are accompanied by three other chronic diseases: smoking, drinking, little exercise, and no light diet are also risk factors for chronic diseases. [ABSTRACT FROM AUTHOR]