PITPNA-AS1 Inhibits Cell Proliferation and Migration in Ovarian Cancer by Regulating the MIR-223-3p/RHOB Axis.

Background: Ovarian cancer is a fatal gynecologic malignancy. Long non-coding RNA (lncRNA) has been verified to serve as key regulator in ovarian cancer tumorigenesis. Objective: The aim of the study was to study the functions and mechanism of lncRNA PITPNA-AS1 in ovarian cancer cellular process. Methods: Clinical ovarian cancer samples were collected and stored at an academic medical center. Cellular fractionation assays and fluorescence in situ hybridization were conducted to locate PITPNA-AS1 in OC cells. TUNEL staining, colony-forming assays, and Transwell assays were performed for evaluating cell apoptosis as well as proliferative and migratory abilities. Western blot was conducted for quantifying protein levels of epithelialmesenchymal transition markers. The binding relation between genes was verified by RNA pulldown, RNA immunoprecipitation, and luciferase reporter assays. Gene expression levels in ovarian cancer tissues and cells were subjected to RT-qPCR. Results: PITPNA-AS1 level was downregulated in ovarian cancer samples and cells. PITPNA-AS1 overexpression contributed to the accelerated ovarian cancer cell apoptosis and inhibited cell migration, proliferation, and epithelial-mesenchymal transition process. In addition, PITPNA-AS1 interacted with miR-223-3p to regulate RHOB. RHOB knockdown partially counteracted the repressive impact of PITPNA-AS1 on ovarian cancer cell activities. Conclusion: PITPNA-AS1 inhibited ovarian cancer cellular behaviors by targeting miR-223-3p and regulating RHOB.

A review regarding the article 'Targeting inflammatory signaling pathways with SGLT2 inhibitors: Insights into cardiovascular health and cardiac cell improvement'.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors have emerged as a novel category of blood glucose-lowering drugs in clinical recommendations for a wide range of diseases. SGLT2 inhibitors are promising anti-inflammatory agents by acting either indirectly via improving metabolism and reducing stress conditions or via direct modulation of inflammatory signaling pathways. The SGLT2 inhibitors empagliflozin and dapagliflozin better vascular function and avert vascular aging by decreasing the reactive oxygen species (ROS) content and increasing nitric oxide bioavailability, respectively. It was discovered that ipragliflozin has the ability to prevent dysfunction of the endothelium, and this effect was connected with oxidative stress. According to published data, SGLT2 inhibitors may delay vascular aging and arrest the development of endothelial dysfunction in animal models of type 2 diabetes (T2D) by reducing inflammation, oxidative stress, and glucose toxicity and increasing the survival of hyperglycemic endothelial cells. The adenosine monophosphate-activated protein kinase (AMPK) molecule plays a vital role in the regulation of bioenergy metabolism and is pivotal in our understanding of diabetes mellitus and other metabolic disorders. It has been hypothesized that SGLT2 inhibitors may indirectly affect AMPK to reduce mammalian target of rapamycin (mTOR) activity. Numerous studies have demonstrated that SGLT2 inhibitors can activate AMPK by restoring the AMP/ATP balance in favor of AMP, which is assumed to be the mechanism by which these medications have positive effects on the cardiac structure and microvessel.

The effects of hyperbaric oxygen therapy on neuroprotection and recovery after brain resuscitation.

OBJECTIVE: Analyze the impact of hyperbaric oxygen therapy on neuroprotection and recovery post severe traumatic brain injury (sTBI) resuscitation. METHODS: Retrospective analysis of clinical data from 83 sTBI patients admitted between January 2022 to January 2024. Patients were divided into control (n = 41) and observation (n = 42) groups based on treatment received. Control received standard therapy, while the observation group received hyperbaric oxygen therapy. Effects on clinical outcomes, neuroinjury markers (S100ß, GFAP, UCH-L1, NSE), neurotrophic factors (NGF, BDNF), neurological function indicators (NIHSS, CSS), and adverse reactions were compared. RESULTS: The observation group showed a higher total effective rate (80.95%) compared to control (60.98%) (p < 0.05). Neuroinjury markers decreased post-treatment in both groups, with the observation group lower (p < 0.05). NGF and BDNF levels increased post-treatment in both groups, with the observation group higher (p < 0.05). NIHSS and CSS scores decreased post-treatment in both groups, with the observation group lower (p < 0.05). No significant difference in adverse reactions between groups (p > 0.05). CONCLUSION: Hyperbaric oxygen therapy effectively treats sTBI by improving brain resuscitation success, reducing neuroinjury factors, enhancing neurotrophic factors, and promoting neurological function recovery, without increasing adverse reaction risk.

Development and effectiveness of a BOPPPS teaching model-based workshop for community pharmacists training.

BACKGROUND/AIM: With the pharmaceutical innovation and clinical knowledge updating, the continuing education and on-the-job training are extremely important for improving community pharmacists' professional competence. Previous training often adopted traditional lecture-based teaching, and the efficacy was limited. The aim of this study is to develop a new strategy for community pharmacist training. METHODS: Based on the BOPPPS (Bridge-in, Objective, Pre-assessment, Participatory Learning, Post-assessment and Summary) teaching model and workshop method, a continuing on-the-job training program was constructed. Participates were randomly and evenly divided into two groups by random number table method. Twenty-four community pharmacists in total completed all training contents and evaluation components in this study. Twelve pharmacists in experimental group were trained via this new BOPPPS-based workshop, while others still adopted traditional didactic lecture-based approaches. RESULTS: After training, quantitative examination combined with clinical pharmacy practice tests were carried out to evaluate the effectiveness and outcomes of two training groups. For written exam, the total scores from the BOPPPS-based workshop group (82.67 ± 4.70) was higher than that of traditional lectured-base group (73.75 ± 6.15) (P < 0.001). Encouragingly, compared with the results of practical ability assessment from traditional training group (71.75 ± 4.75), the pharmacists receiving BOPPPS-based workshop training presented more excellent performance (78.25 ± 5.03), which displayed statistically significant differences (P < 0.01). In addition, an anonymous questionnaire was used to survey trainees' feelings after completing this continuing education program. The results revealed that the BOPPPS-based workshop can bring a better learning experience than traditional lecture-based training, and the percentages of positive response to each item were more than 91.7%. CONCLUSIONS: Through multi-dimensional evaluation, it was suggested that our BOPPPS-based workshop achieved desired training effects. Moreover, our research also demonstrated that this strategy had advantages of stimulating inspiration, autonomous learning, team-work spirit and pharmacy practice improvement. It may provide a reference of innovative training method for community pharmacists.

Ultrasound blood flow characteristics changes in fetal umbilical artery thrombosis: A retrospective analysis.

BACKGROUND: Umbilical artery thrombosis (UAT) is extremely uncommon and leads to adverse perinatal outcomes. Hypercoagulation of blood in pregnant women is suspected to be an important risk for UAT. Ultrasound is an effective way to detect thrombosis. The mother can monitor her own fetal health using ultrasound, which enables her to take preventative action in case of emergency. AIM: To investigate ultrasonic blood signal after UAT in the umbilical artery, and evaluate the relationship between hypercoagulability and UAT. METHODS: We described a case of a newly formed UAT with markedly altered ultrasonic indices of umbilical artery blood flow, and retrospectively studied it with 18 UAT patients confirmed by histopathology from October 2019 and March 2023 in Xiamen Women and Children's Hospital. Patients' information was collected from medical archives, including maternal clinical data, neonatal outcomes, pathological findings and ultrasonic indices of umbilical artery blood flow, such as systolic-diastolic duration ratio (S/D), resistance index (RI), pulsatility index (PI) and peak systolic velocity (PSV). Ultrasound and coagulation indices were analyzed with matched samples t-test and Wilcoxon rank sum test using the statistical packages in R (version 4.2.1) including car (version 3.1-0) and stats (version 4.2.1), and visualized by ggplot2 package (version 3.3.6). RESULTS: A patient with normal findings in second and third-trimester routine ultrasound scan developed UAT with severe changes in ultrasonic indices of umbilical artery blood flow (within 2.5th of reference ranges) in a short period of time. Statistical analysis of umbilical artery blood flow ultrasound indices for 19 patients with UAT showed that the decrease in S/D, RI, and PI and increase of PSV during the disease process was greater than that of non-UAT. All 18 patients delivered in our hospital showed characteristic manifestations of UAT on histological examination after delivery, most of which (16/18) showed umbilical cord abnormalities, with 15 umbilical cord torsion and 1 pseudoknot. Coagulation parameters were not significantly changed in UAT patients compared with normal pregnancy women. CONCLUSION: Significant changes in ultrasound indicators after UAT were demonstrated. PSV can play important roles in the diagnosis of UAT. Hypercoagulability alone is not sufficient for the occurrence of UAT.

Stachyose in combination with L. rhamnosus GG ameliorates acute hypobaric hypoxia-induced intestinal barrier dysfunction through alleviating inflammatory response and oxidative stress.

High altitude is closely related to intestinal mucosal damage and intestinal microbiota imbalance, and there is currently no effective prevention and treatment measures. In this study, the effects of stachyose (STA), L. rhamnosus GG (LGG) and their combination on inflammatory response, oxidatve stress and intestinal barrier function in mice exposed to acute hypobaric hypoxia were investigated. Our results indicated the combination of STA and LGG could more effectively regulate intestinal microbiota disorders caused by hypobaric hypoxia than STA or LGG alone. When mice were administered with STA + LGG, the content of short chain fatty acids (SCFAs) especially butyric acid significantly increased, which helped intestinal cells to form tight connections, improve the level of anti-inflammatory cytokine (TGF-ß) and antioxidant enzymes (SOD, CAT, GSH-Px), and decrease the expression of pro-inlammatory cytokines and hypoxia-inducing factors (IFN-γ, IL-1ß, IL-6, TNF-α and HIF-1α), thereby enhance the strong intestinal barrier function. Furthermore, the synbiotics significantly reduced the ratio of Firmicutes to Bacteroidetes, while significantly increased the relative abundance of Rikenella, Bacteroides, Odoribacter, Ruminiclostridium_5 and Gordonibacter, which were correlated with production of SCFAs and anti-inflammatory role. Correlation analysis showed that the protective effect of synbiotics on intestinal barrier function was associated with its anti-inflammatory activity and antioxidant capacity. It provided a strong foundation for further research on the role of STA and LGG in maintaining normal intestinal function at high altitude. Our study has identified and demonstrated a new synbiotic that may be one of the ideal intervention measures for preventing and treating intestinal dysfunction at high altitude.

Deep learning system improved detection efficacy of fetal intracranial malformations in a randomized controlled trial.

Congenital malformations of the central nervous system are among the most common major congenital malformations. Deep learning systems have come to the fore in prenatal diagnosis of congenital malformation, but the impact of deep learning-assisted detection of congenital intracranial malformations from fetal neurosonographic images has not been evaluated. Here we report a three-way crossover, randomized control trial (Trial Registration: ChiCTR2100048233) that assesses the efficacy of a deep learning system, the Prenatal Ultrasound Diagnosis Artificial Intelligence Conduct System (PAICS), in assisting fetal intracranial malformation detection. A total of 709 fetal neurosonographic images/videos are read interactively by 36 sonologists of different expertise levels in three reading modes: unassisted mode (without PAICS assistance), concurrent mode (using PAICS at the beginning of the assessment) and second mode (using PAICS after a fully unaided interpretation). Aided by PAICS, the average accuracy of the unassisted mode (73%) is increased by the concurrent mode (80%; P < 0.001) and the second mode (82%; P < 0.001). Correspondingly, the AUC is increased from 0.85 to 0.89 and to 0.90, respectively (P < 0.001 for all). The median read time per data is slightly increased in concurrent mode but substantially prolonged in the second mode, from 6 s to 7 s and to 11 s (P < 0.001 for all). In conclusion, PAICS in both concurrent and second modes has the potential to improve sonologists' performance in detecting fetal intracranial malformations from neurosonographic data. PAICS is more efficient when used concurrently for all readers.

The Association Between Mild Cognitive Impairment and Medication Non-adherence Among Elderly Patients With Chronic Diseases.

BACKGROUND: Medication adherence is essential for optimizing treatment outcomes in elderly patients who frequently contend with multiple chronic diseases requiring pharmacological interventions. Mild cognitive impairment (MCI) is a prevalent cognitive disorder among the elderly population, but its impact on medication adherence among elderly patients is still uncertain. This cross-sectional study aimed to investigate the impact of MCI on medication adherence among elderly patients. METHODS: A cross-sectional study of 436 elderly patients with common chronic diseases aged 60 years and above was conducted. Medication adherence was measured using the Morisky Medication Adherence Scale-8 (MMAS-8). MCI was screened, and cognitive status was assessed using the Mini-Mental State Examination (MMSE) questionnaire. Multivariate logistic regression analysis was performed to identify independent risk factors of medication non-adherence. RESULTS: Among these elderly patients, 212 (48.6%) had poor medication compliance, and 181 (41.5%) had MCI. Preliminary analyses showed a significant association between MCI and medication non-adherence among elderly patients (odds ratio (OR)=3.95, 95% confidence interval (95%CI)=2.63-5.92, P<0.001). Multivariate logistic regression analysis showed that MCI was independently associated with the risk of medication non-adherence among elderly patients (adjusted OR=2.64, 95%CI=1.64-4.24, P<0.001). Additionally, adverse drug reaction and poor evaluation of medication effects were also independently associated with medication non-adherence in elderly patients (P<0.05). CONCLUSION: Findings from this cross-sectional study proved the substantial adverse impact of MCI on medication adherence among elderly patients, and MCI was an independently influential factor of medication non-adherence. Identifying the MCI status early and providing interventions to enhance medication adherence are undoubtedly essential for optimizing healthcare outcomes in elderly patients.

Extreme hepatectomy with modified ALPPS in a rat model: gradual portal vein restriction associated with hepatic artery restriction.

BACKGROUND & AIM: Associating liver partition and portal vein ligation (PVL) for staged hepatectomy (ALPPS) is a creative strategy for enlarging the future liver remnant (FLR) and increasing the tumor resectability rate. However, the indications for ALPPS must have a certain limit when the FLR is too small. We aimed to establish a modified ALPPS model with more widen applicability in rats. METHODS: An extreme ALPPS model was established in rodents with only a 6.5% FLR. The portal vein (PV) was subjected to restriction to different degrees, then the portal vein pressure (PVP) was measured. Then, different modifications of ALPPS, including hepatic artery restriction (HAR), gradual portal vein restriction (GPVR), and GPVR-associated HAR (HAR+GPVR), were applied in the extreme ALPPS models. RESULTS: PVL or PVR provoked an immediate increase in the PVP. The PVP in the PVR -1.28 mm, PVR -0.81 mm, PVR -0.63 mm, and PVL groups was 11.05±1.57 cmH2O, 16.18±1.92 cmH2O, 20.66±1.99 cmH2O, and 24.10±3.33 cmH2O, respectively, and the corresponding 3-day survival rate was 100%, 90.09%, 36.33% and 0, respectively. Then, in the extreme ALPPS model, the growth ratio of the FLR in the control, HAR, GPVR, and HAR+GPVR groups was 0.43±0.21, 0.50±0.16, 4.80±0.86, and 7.40±2.56, and as a consequence, the corresponding 30-day survival rate was 9.09%, 15.38%, 84.61% and 92.90%, respectively. CONCLUSION: ALPPS itself has a limit, and high PVP after PVL contributes to postoperative death in the extreme ALPPS model. Furthermore, a modified method for extreme ALPPS is proposed, i.e., GPVR+HAR in place of PVL, which significantly improves the survival rate of extreme hepatectomy in rat models.

Effect of Lacticaseibacillus paracasei strain Shirota supplementation on clinical responses and gut microbiome in Parkinson's disease.

Parkinson's disease (PD) is a common neurodegenerative disease characterized by motor issues and a range of non-motor symptoms. Microbial therapy may be a useful approach for the treatment of PD. However, comprehensive analyses of the impact of probiotic supplementation on motor and non-motor symptoms are still lacking and the mechanisms whereby the treatment works remain unclear. This study investigated Lacticaseibacillus paracasei strain Shirota (LcS) supplementation on clinical responses, gut microbiota and faecal metabolites in PD patients. Patients (n = 128) were randomised to receive either probiotics (LcS-fermented milk, containing 1 × 1010 living LcS cells) or placebo for 12 weeks. All participants were examined and the basic clinical features were recorded using questionnaires. Fecal and blood samples were collected at the baseline and after 12 weeks for further omics analysis. We found that LcS intervention significantly alleviated patients' constipation-related symptoms and non-motor symptoms. We found no significant shifts in the composition of gut microbiota or faecal metabolites. Several taxa were differentially abundant between the groups, especially with regard to LcS intake, which increased the abundance of the genus Lacticaseibacillus in the probiotic group compared with those at the baseline and in the placebo group. The faecal concentration of L-tyrosine was significantly decreased and the plasma concentration of L-tyrosine was increased in the probiotic group compared with the placebo group. Our study demonstrated that although supplementation with LcS did not induce major changes in the global gut microbiome, the probiotic had favorable effects in managing constipation and other non-motor symptoms in PD patients. This study was registered at the Chinese Clinical Trial Registry: ChiCTR1800016795.

Extended Ligation of the Hepatic Vein May Yield a Similar Effect to Liver Venous Deprivation in a Rat Model.

AIMS: To validate the hypothesis that hepatic vein ligation (HVL) alone may produce similar results to liver venous deprivation (LVD or HVL + portal vein ligation [PVL]). METHODS: Rats were assigned to five groups, namely, the control group; the R group in which the right median hepatic vein (RMHV) was ligated; the M group in which the middle median hepatic vein (MMHV) was ligated; the RM group in which both the RMHV and MMHV were ligated (R + MMHVL, extended ligation of the hepatic veins); and the LVD group in which both the right median portal vein and the RMHV were ligated. The liver hypertrophy effect and liver enzymes were determined. Methylene blue staining and retrograde pressurized perfusion assays were performed to investigate the hemodynamic changes. RESULTS: The RM and LVD groups exhibited similar significant hypertrophy in the future liver remnants when compared to that of the control group, and almost no additional hypertrophy effect was observed in the R and M groups. There was a remarkable elevation in serum transaminase levels in both groups. The methylene blue staining experiment indicated that pressure-dependent collaterals formed between the contiguous drainage areas, and the R + MMHVL procedure blocked the outflow of the right median lobe. CONCLUSION: Extended ligation of the hepatic vein (R + MMHVL) resulted in a similar hypertrophy effect and hepatic damage to those of LVD (HVL + PVL) treatment in a rat model, and intrahepatic venovenous collaterals play key roles.

Poor performance of malaria rapid diagnostic tests for the detection of Plasmodium malariae among returned international travellers in China.

BACKGROUND: Malaria is a worldwide infectious disease. For countries that have achieved malaria elimination, the prevention of re-establishment due to infections in returned travellers has become important. The accurate and timely diagnosis of malaria is the key in preventing re-establishment, and malaria rapid diagnostic tests (RDTs) are frequently used due to their convenience. However, the RDT performance in Plasmodium malariae (P. malariae) infection diagnosis remains unknown. METHODS: This study analysed epidemiological features and diagnosis patterns of imported P. malariae cases from 2013 to 2020 in Jiangsu Province and evaluated the sensitivity of four parasite enzyme lactate dehydrogenase (pLDH)-targeting RDTs (Wondfo, SD BIONLINE, CareStart and BioPerfectus) and one aldolase-targeting RDT(BinaxNOW) for P. malariae detection. Furthermore, influential factors were investigated, including parasitaemia load, pLDH concentration and target gene polymorphisms. RESULTS: The median duration from symptom onset to diagnosis among patients with P. malariae infection was 3 days, which was longer than that with Plasmodium falciparum (P. falciparum) infection. The RDTs had a low detection rate (39/69, 56.5%) among P. malariae cases. All tested RDT brands had poor performance in P. malariae detection. All the brands except the worst-performing SD BIOLINE, achieved 75% sensitivity only when the parasite density was higher than 5000 parasites/µL. Both pLDH and aldolase showed relatively conserved and low gene polymorphism rates. CONCLUSIONS: The diagnosis of imported P. malariae cases was delayed. The RDTs had poor performance in P. malariae diagnosis and may threaten the prevention of malaria re-establishment from returned travellers. The improved RDTs or nucleic acid tests for P. malariae cases are urgently needed for the detection of imported cases in the future.

DeepGA for automatically estimating fetal gestational age through ultrasound imaging.

Accurate estimation of gestational age (GA) is vital for identifying fetal abnormalities. Conventionally, GA is estimated by measuring the morphology of the cranium, abdomen, and femur manually and inputting them into the classic Hadlock formula to assess fetal growth. However, this procedure incurs considerable overhead and suffers from bias caused by the operators, yielding suboptimal estimations. To address this challenge, we develop an automatic DeepGA model to achieve fully automatic GA prediction in an end-to-end manner. Our model uses a deep segmentation model (DeepSeg) to accurately identify and segment three critical tissues, including the cranium, abdomen, and femur, in which their morphology is automatically extracted. After that, we are able to directly estimate the GA via a deep regression model (DeepReg). We evaluate DeepGA on a large dataset, including 10,413 ultrasound images from 7113 subjects. It achieves superior performance over the traditional measurement approach, with a mean absolute estimation error (MAE) of 5 days. Our DeepGA model is a novel automatic solution on the basis of artificial intelligence learning that can help radiologists improve the performance of GA estimation in various clinical scenarios, thereby enhancing the efficiency of prenatal examinations.

Establishment of a Rat Model of Liver Venous Deprivation: Simultaneous Portal and Hepatic Vein Ligation.

Background and Aims: The aim was to establish a liver venous deprivation (LVD) model in rats, compare hepatic hypertrophy between LVD and associated liver partition and portal vein ligation for staged hepatectomy (ALPPS), and explore the underlying mechanisms. Methods: The LVD or extended-LVD (e-LVD) group received portal vein ligation (PVL) combined with hepatic vein ligation (HVL). The ALPPS or e-ALPPS group received PVL plus parenchyma ligation. Liver regeneration was assessed by measuring the liver weight and performing pathological analysis. Liver functions and the sphingosine kinase 1 (SPHK1)/sphingosine-1-phosphate (S1P)/sphingosine-1-phosphate receptor 1 (S1PR1) pathway were also investigated. Results: All future liver remnants (FLRs) in the ALPPS, e-ALPPS, LVD, and e-LVD groups exhibited significant hypertrophy compared with the control group. The LVD and e-LVD procedures induced similar liver hypertrophy than that in the corresponding ALPPS groups. Furthermore, the LVD and e-LVD methods led to obvious cytolysis in the venous-deprived lobes as well as a noticeable increase in serum transaminase levels, while no necrosis was observed in the ALPPS and e-ALPPS groups. SPHK1/S1P/S1PR1 pathway were distinctly activated after operation, especially in congestive/ischemic livers. Conclusions: We describe the first rat model of LVD and e-LVD with simultaneously associated HVL and PVL. Compared with the ALPPS technique, the LVD or e-LVD procedure had a comparable overall effect on the hypertrophy response and a stronger effect on liver function. The SPHK1/S1P/S1PR1 pathway was involved in the LVD- or ALPPS-induced liver remodeling.

The application of nanoparticles in immunotherapy for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related deaths worldwide, however, current clinical diagnostic and treatment approaches remain relatively limited, creating an urgent need for the development of effective technologies. Immunotherapy has emerged as a powerful treatment strategy for advanced cancer. The number of clinically approved drugs for HCC immunotherapy has been increasing. However, it remains challenging to improve their transport and therapeutic efficiency, control their targeting and release, and mitigate their adverse effects. Nanotechnology has recently gained attention for improving the effectiveness of precision therapy for HCC. We summarize the key features of HCC associated with nanoparticle (NPs) targeting, release, and uptake, the roles and limitations of several major immunotherapies in HCC, the use of NPs in immunotherapy, the properties of NPs that influence their design and application, and current clinical trials of NPs in HCC, with the aim of informing the design of delivery platforms that have the potential to improve the safety and efficacy of HCC immunotherapy，and thus, ultimately improve the prognosis of HCC patients.

Association Between Microbial Tyrosine Decarboxylase Gene and Levodopa Responsiveness in Patients With Parkinson Disease.

BACKGROUND AND OBJECTIVES: Interindividual variability in levodopa efficacy is a challenge for the personalized treatment of Parkinson disease (PD). Gut microbiota might represent a new approach for personalized medicine. Recently, a novel microbial levodopa metabolism pathway was identified, which is mediated by tyrosine decarboxylase mainly encoded by tyrosine decarboxylase gene (tyrDC) in Enterococcus faecalis. In this study, we aimed to identify whether the abundance of microbial tyrDC gene and E faecalis is associated with levodopa responsiveness and could predict the drug response. METHODS: This cross-sectional study enrolled patients with PD between December 2019 and January 2022 and evaluated levodopa responsiveness using a levodopa challenge test. Patients were stratified into moderate and good responders based on levodopa responsiveness. The tyrDC gene and E. faecalis abundance in fecal samples were measured using quantitative real-time PCR. Plasma levodopa concentrations were measured using liquid chromatography-tandem mass spectrometry analysis. The predictive models for levodopa responsiveness were constructed and verified through cross-validation and external validation. RESULTS: A total of 101 patients with PD were enrolled in the primary cohort and 43 were enrolled in the external validation cohort. Moderate responders had higher abundances of the tyrDC gene (3.6 [3.1-4.3] vs 2.6 [2.1-2.9], p < 0.001) and E faecalis (3.2 [2.5-4.4] vs 2.6 [2.1-3.6], p = 0.010) than good responders. The tyrDC gene abundance was independently associated with levodopa responsiveness (OR: 5.848; 95% CI: 2.664-12.838; p < 0.001). Notably, tyrDC gene abundance showed certain discriminative power for levodopa responsiveness in primary cohort (sensitivity: 80.0%; specificity: 84.3%; area under the curve [AUC]: 0.85; 95% CI: 0.77-0.93; p < 0.001) and external validation cohort (sensitivity: 85.0%; specificity: 95.7%; AUC: 0.95; 95% CI: 0.89-1.02; p < 0.001). The prediction of levodopa responsiveness based on tyrDC gene abundance had good calibration and discrimination in cross-validation (C-index in training and test sets: 0.856 and 0.851, respectively) and external validation (C-index: 0.952). DISCUSSION: The microbial tyrDC gene abundance could serve as a potential biomarker of levodopa responsiveness. Novel strategies targeting the tyrDC gene may provide new approaches for personalized levodopa treatment.

Co-Fermentation of Edible Mushroom By-Products with Soybeans Enhances Nutritional Values, Isoflavone Aglycones, and Antioxidant Capacity of Douchi Koji.

Douchi is a traditional salt-fermented soybean food with various bioactivities, such as anti-oxidation, anti-diabetes, and anti-hypertension, which are greatly affected by the activities of protease and ß-glucosidase during koji production. Edible mushroom by-products are ideal ingredients for enhancing food flavor and nutritional quality due to their unique nutritional characteristics of high protein, rich amino acids, and low calories. However, there is no research on the preparation of Douchi by the mixed fermentation of edible mushroom by-products and soybeans. In this study, response surface methodology (RSM) was used to optimize the fermentation conditions of edible mushroom by-product Douchi koji (EMDK) with protease and ß-glucosidase activities as indicators, and the changes in the main bioactive compounds and antioxidant activities of unfermented raw samples (URS), Douchi koji without edible mushroom by-product (DKWE), and EMDK were compared. The results of single-factor tests and RSM showed that the optimal fermentation conditions of EMDK were the Aspergillus oryzae to Mucor racemosus ratio of 1:1, inoculation amount of 6%, edible mushroom amount of 21%, and fermentation time of 63 h, and the activities of protease and ß-glucosidase under these conditions were 796.03 ± 15.01 U/g and 1175.40 ± 36.98 U/g, respectively. Additionally, compared with URS and DKWE, the contents of total isoflavones and ß-glucoside isoflavones in EMDK were notably decreased, while the contents of amino nitrogen, total phenolics, total flavonoids, and aglycone isoflavone, as well as the antioxidant capacity were significantly increased. Furthermore, significant correlations were found between the above components and antioxidant capacity. These results showed that edible mushroom by-product could be incorporated into soybeans for co-fermentation, conferring higher nutritional value to and antioxidant capacity of Douchi koji.

Efficacy and safety of acupuncture in the treatment of the sequela of olfactory disorders after infection with COVID-19: A protocol for systematic review and meta analysis.

BACKGROUND: From the end of 2019 to now, coronavirus disease 2019 (COVID-19) has put enormous strain on the world's health systems. As a characteristic sign of COVID-19 patient, olfactory dysfunction (OD) poses considerable problems for patients. In China, acupuncture has been widely used to treat OD caused by COVID-19, but there is still a lack of evidence-based medical evaluation. This study was designed to evaluate the effectiveness and safety of acupuncture for the treatment of COVID-19 OD. METHODS: According to the retrieval strategies, randomized controlled trials on the acupuncture for COVID-19 OD were obtained from Cochrane Central Register of Controlled Trials, Embase, PubMed, Web of Science, the Chinese National Knowledge Infrastructure, the Chinese Biomedical Literature Database, the Chinese Scientific Journal Database and the Wanfang Database, regardless of publication date, or language. Studies were screened based on inclusion and exclusion criteria, and the Cochrane risk bias assessment tool was used to evaluate the quality of the studies. The meta-analysis was performed using Review Manager (RevMan 5.3) and STATA 14.2 software. Ultimately, the evidentiary grade for the results will be evaluated. RESULTS: The results of this meta-analysis will be submitted to a peer-reviewed journal for publication. CONCLUSION: This study will provide up-to-date summary proof for evaluating the effectiveness and safety of acupuncture for COVID-19 OD.

Tumor-Suppressive and Oncogenic Roles of microRNA-149-5p in Human Cancers.

Malignant tumors are always a critical threat to human health, with complex pathogenesis, numerous causative factors, and poor prognosis. The features of cancers, such as gene mutations, epigenetic alterations, and the activation and inhibition of signaling pathways in the organism, play important roles in tumorigenesis and prognosis. MicroRNA (miRNA) enables the control of various molecular mechanisms and plays a variety of roles in human cancers, such as radiation sensitivity and tumor immunity, through the regulation of target genes. MiR-149-5p participates in the process and is closely related to lipogenesis, the migration of vascular endothelial cells, and the expression of stem-cell-related proteins. In recent years, its role in cancer has dramatically increased. In this review, we summarize the regular physiological roles of miRNAs, specifically miR-149-5p, in the organism and discuss the tumor-suppressive or oncogenic roles of miR-149-5p in different human cancers with respect to signaling pathways involved in regulation. Possible clinical applications of miR-149-5p in future targeted therapies and prognosis improvement in oncology are suggested.