High-dose amoxicillin-proton pump inhibitor dual therapy as first-line treatment for Helicobacter pylori infection in Northwest China: A prospective, randomised controlled trial.

AIMS: We aimed to assess the eradication efficacy and factors that influencing it of high-dose dual therapy (HDDT) in Gansu region, Northwest China. METHODS: A total of 216 treatment-naive patients with Helicobacter pylori infection were randomly assigned to two groups for the 14-day eradication treatment: the HDDT group (amoxicillin 750 mg q.i.d. and esomeprazole 40 mg t.i.d.) and the amoxicillin and clarithromycin-containing bismuth quadruple therapy group (ACBQT: esomeprazole 20 mg, bismuth potassium citrate 2 g, amoxicillin 1 g, and clarithromycin 500 mg; b.i.d.). The eradication rates, adverse effects and patient compliance of these two groups were compared. Eradication efficacy was determined by 13 C urea breath test (13 C UBT) 4-8 weeks after finishing treatment. Antibiotic resistance was determined by the Epsilometer testing (E-test) method. RESULTS: The eradication rates for the HDDT and ACBQT groups were 71.0% and 74.7% (P = .552) by per-protocol analysis, and 65.7% and 68.5% (P = .664) by intention-to-treat analysis. The overall adverse event rates in the HDDT and ACBQT groups were 2.0% and 43.4% (P < .001), respectively. The resistance rates to amoxicillin, clarithromycin, tetracycline, levofloxacin and metronidazole were 15.2%, 42.0%, 5.4%, 35.7% and 83.0%, respectively. Amoxicillin resistance and delta over baseline (DOB) of 13 C UBT ≥ 20 before treatment significantly reduced the eradication rate in 112 participants with H. pylori cultured. CONCLUSION: The HDDT as first-line treatment for H. pylori was unsatisfactory in Gansu. Amoxicillin resistance and DOB of 13 C UBT ≥ 20 before treatment were significantly correlated with H. pylori eradication failure.

Single boll weight depends on photosynthetic function of boll-leaf system in field-grown cotton plants under water stress.

Cotton has many leaves and even more bolls, which results in a complicated source-sink relationship. Under water stress, the single boll weight (SBW) of cotton remains relatively stable, while both the leaf area and leaf photosynthetic rate decrease greatly. It is therefore difficult to understand how the formation of SBW is regulated under water stress solely by considering single-leaf photosynthesis. Considering the cotton boll-leaf system (BLS: including the main-stem leaf, sympodial leaves, and non-leaf organs) as the basic unit of the cotton canopy, we speculated that the formation of SBW may depend on photosynthesis in the corresponding BLS under water stress. To verify this hypothesis, five water treatments were set up in the field. The results showed that with increasing water stress, the relative water content (RWC) of the main-stem and sympodial leaves decreased gradually, and the decrease in the sympodial leaves was more obvious. The SBW and the number of BLSs decreased slightly with increasing water stress, while the number of bolls per plant decreased significantly. The area of the BLS decreased gradually with increasing water stress, and the area of sympodial leaves decreased more than that of the main-stem leaves. Gas exchange showed that the photosynthetic rate of the BLS (Pn(BLS)) decreased gradually with increasing water stress. In addition, the single-leaf photosynthesis and carboxylation efficiency (CE) decreased progressively and rapidly with the increase of water stress. Compared with the main-stem leaf, the photosynthetic function of the sympodial leaf decreased more. Further analysis showed that compared with leaf photosynthetic rate, there was a better correlation between Pn(BLS) and SBW. Thus, the formation of SBW mainly depends on Pn(BLS) under water stress, and the increase of BLS to boll is also helpful to maintain SBW to some extent. In BLS, the photosynthesis of the main-stem leaf plays a very important role in maintaining the stability of SBW, while the photosynthetic performance in sympodial leaves may be regulated plastically to influence SBW.

Sarsasapogenin ameliorates diabetes-associated memory impairment and neuroinflammation through down-regulation of PAR-1 receptor.

Sarsasapogenin (Sar), a natural steroidal compound, shows neuroprotection, cognition-enhancement, antiinflammation, antithrombosis effects, and so on. However, whether Sar has ameliorative effects on diabetes-associated cognitive impairment remains unknown. In this study, we found that Sar ameliorated diabetes-associated memory impairment in streptozotocin-induced diabetic rats, evidenced by increased numbers of crossing platform and percentage of time spent in the target quadrant in Morris water maze tests, and suppressed the nucleotide-binding domain and leucine-rich repeat containing protein 1 (NLRP1) inflammasome in hippocampus and cerebral cortex. Furthermore, Sar inhibited advanced glycation end-products and its receptor (AGEs/RAGE) axis and suppressed up-regulation of thrombin receptor protease-activated receptor 1 (PAR-1) in cerebral cortex. On the other hand, Sar mitigated high glucose-induced neuronal damages, NLRP1 inflammasome activation, and PAR-1 up-regulation in high glucose-cultured SH-SY5Y cells, but did not affect thrombin activity. Moreover, the effects of Sar were similar to those of a selective PAR-1 antagonist vorapaxar. Further studies indicated that activation of the NLRP1 inflammasome and NF-κB mediated the effect of PAR-1 up-regulation in high glucose condition by using PAR-1 knockdown assay. In summary, this study demonstrated that Sar prevented memory impairment caused by diabetes, which was achieved through suppressing neuroinflammation from activated NLRP1 inflammasome and NF-κB regulated by cerebral PAR-1. HIGHLIGHTS: Sarsasapogenin ameliorated memory impairment caused by diabetes in rats. Sarsasapogenin mitigated neuronal damages and neuroinflammation by down-regulating cerebral PAR-1. The NLRP1 inflammasome and NF-κB signaling mediated the pro-inflammatory effects of PAR-1. Sarsasapogenin was a pleiotropic neuroprotective agent and memory enhancer in diabetic rodents.

Development of a nomogram for predicting nasogastric tube-associated pressure injuries in intensive care unit patients.

Here, we aimed to build a nomogram model to estimate the probability of nasogastric tube-associated pressure injuries (NTAPIs) in intensive care unit(ICU)patients. This prospective cohort study included 219ICU patients with nasogastric tube between September 2019 and January 2020.Univariate and multivariate logistic regression analyses were used to develop the nomogram model. The resulting nomogram was tested for calibration, discrimination, and clinical usefulness. Of the included patients, 58 developed NTAPIs, representing an incidence rate of 26.5%. Binary logistic regression analysis revealed that the prediction nomogram included C-reactive protein, vasopressor use, albumin level, nasogastric tube duration, and Sequential Organ Failure Assessment score. The value of these predictors was again confirmed using theLasso regression analysis. Internal validation presented a good discrimination of the nomogram, with an area under the curve value of 0.850, and good calibration (Hosmer-Lemeshow test, P = 0.177). The decision curve analysis also demonstrated preferable net benefit along with the threshold probability in the prediction nomogram. The nomogram model can accurately predict the risk factors for NTAPIs, to formulate intervention strategies as early as possible to reduce NTAPI incidence.

Knowledge, attitude, and practice of nurses in intensive care unit on preventing medical device-related pressure injury: A cross-sectional study in western China.

The knowledge, attitude, and practice of nurses in intensive care units (ICUs) are determinants for the efficacy of preventing the medical device-related pressure injury (MDRPI). The aim of this study was to determine the level and factors of knowledge, attitude, and practice of nurses' ICUs on preventing medical MDRPI in western China. An annual cross-sectional study was conducted in hospitals of western China from May 2020 to September 2020. Nurses' knowledge and attitudes were assessed using Clinical Nurses Prevention MDRPI of Critically Ill Patients for the Knowledge, Attitude, Practice Assessment Scale. SPSS software version 25.0 and independent t-test, Chi-square, Fisher exact, one-way analysis of variance, and multiple linear regression tests were used for data analysis. A total of 1002 nurses in ICUs from 37 hospitals in Gansu Province, China, participated in this study. The scores of overall KAP, knowledge, attitudes, and practice were 149.17 ± 24.62, 53.83 ± 12.23, 37.24 ± 6.35 and 58.10 ± 9.83, respectively. There was a positive and significant relationship between three variables. Findings revealed that nurses' knowledge score in the Tertiary hospital was higher than scores of other hospitals as 3.840 units. Moreover, the knowledge score and practice score of nurses with bachelor's degree or above were higher than other nurses and are 0.978 and 1.106 units, respectively. Based on the findings, practice of nurses increased by 0.992 units, with a 1-year increase in work experience of nurses in the ICU. The levels of knowledge, attitude, and practice of nurse in ICUs on preventing MDRPI were acceptable. The findings of the study highlight that a comprehensive approach should be conducted for raising the level of knowledge, attitude, and practice of nurses' ICUs on preventing medical MDRPI, as well as improving the quality of care for critically ill patients.

SPZ1 promotes deregulation of Bim to boost apoptosis resistance in colorectal cancer.

Colorectal cancer (CRC) is the third most common malignancies in adults. Similar to other solid tumors, CRC cells show increased proliferation and suppressed apoptosis during the development and progression of the disease. Previous studies have shown that a novel tumor oncogene, spermatogenic basic helix-loop-helix transcription factor zip 1 (SPZ1), can promote proliferation. However, it is unclear whether SPZ1 plays a role in suppressing apoptosis, and the molecular mechanism behind SPZ1's suppression of apoptosis in CRC remains unclear. Here, we found that silencing endogenous SPZ1 inhibits cell growth and induces apoptosis, and overexpression of SPZ1 promotes cell growth. These findings were corroborated by in vitro and in vivo studies. Interestingly, SPZ1 overexpressing cells were resistant to 5-fluorouracil, a drug commonly used to treat cancer. Moreover, knocking down SPZ1 led to the activation of caspase through the deregulation of Bim by ERK1/2, we found that CRC tissues had significantly higher SPZ1 and lower Bim expression, and SPZ1HBimL were associated with advanced clinical stage of CRC. Collectively, our findings demonstrate that SPZ1 contributes to tumor progression by limiting apoptosis. SPZ1 reduces apoptosis by altering the stability of Bim, suggesting SPZ1 may serve as a biomarker and therapeutic target for CRC.

[Cloning of Guamerin gene in Whitmania pigra and its spatio-temporal expression analysis after ingestion].

The present study cloned wpGuamerin gene from a non-bloodsucking leech (Whitmania pigra), and the bioinformatics analysis of the sequence was performed. Additionally, the effects of feeding duration on the expression profile of the wp Guamerin gene were explored. The results showed that its sequence consisted of 295 nucleotides encoding a peptide of 83 amino acids(Genbank: KX768545), and its relative molecular weight is 9 145.95 Da. wp Guamerin does not encode proteins with a signal peptide, belonging to the hydrophilic protein. Its secondary structure is mainly composed of α-helix, extending chain, folding and random curl. Its similarity with other blood-sucking leeches ranges from 29% to 65%. The results revealed that wpGuamerin mRNA was detected higher expression in muscle than in salivary glands of Wh. pigra, and did not expressed in ingluvies and intestine. Its expression in muscle and salivary glands showed a single peak curve after feeding and the peak was observed in the 1st and 3rd after feeding, respectively. In summary, wp Guamerin in Wh. pigra is a small molecule polypeptide protein and is different from the Guamerin in blood-sucking leeches. wpGuamerin does not express in the digestive tract of Wh. pigra, and mainly express in muscle. Feeding behavior would stimulate the expression of wpGuamerin gene in muscle and salivary glands, but not in digestive tract.

An ontology-based approach to patient follow-up assessment for continuous and personalized chronic disease management.

OBJECTIVE: Chronic diseases are complex and persistent clinical conditions that require close collaboration among patients and health care providers in the implementation of long-term and integrated care programs. However, current solutions focus partially on intensive interventions at hospitals rather than on continuous and personalized chronic disease management. This study aims to fill this gap by providing computerized clinical decision support during follow-up assessments of chronically ill patients at home. METHODS: We proposed an ontology-based framework to integrate patient data, medical domain knowledge, and patient assessment criteria for chronic disease patient follow-up assessments. A clinical decision support system was developed to implement this framework for automatic selection and adaptation of standard assessment protocols to suit patient personal conditions. We evaluated our method in the case study of type 2 diabetic patient follow-up assessments. RESULTS: The proposed framework was instantiated using real data from 115,477 follow-up assessment records of 36,162 type 2 diabetic patients. Standard evaluation criteria were automatically selected and adapted to the particularities of each patient. Assessment results were generated as a general typing of patient overall condition and detailed scoring for each criterion, providing important indicators to the case manager about possible inappropriate judgments, in addition to raising patient awareness of their disease control outcomes. Using historical data as the gold standard, our system achieved a rate of accuracy of 99.93% and completeness of 95.00%. CONCLUSIONS: This study contributes to improving the accessibility, efficiency and quality of current patient follow-up services. It also provides a generic approach to knowledge sharing and reuse for patient-centered chronic disease management.

Design and Development of a Sharable Clinical Decision Support System Based on a Semantic Web Service Framework.

Clinical decision support (CDS) systems provide clinicians and other health care stakeholders with patient-specific assessments or recommendations to aid in the clinical decision-making process. Despite their demonstrated potential for improving health care quality, the widespread availability of CDS systems has been limited mainly by the difficulty and cost of sharing CDS knowledge among heterogeneous healthcare information systems. The purpose of this study was to design and develop a sharable clinical decision support (S-CDS) system that meets this challenge. The fundamental knowledge base consists of independent and reusable knowledge modules (KMs) to meet core CDS needs, wherein each KM is semantically well defined based on the standard information model, terminologies, and representation formalisms. A semantic web service framework was developed to identify, access, and leverage these KMs across diverse CDS applications and care settings. The S-CDS system has been validated in two distinct client CDS applications. Model-level evaluation results confirmed coherent knowledge representation. Application-level evaluation results reached an overall accuracy of 98.66 % and a completeness of 96.98 %. The evaluation results demonstrated the technical feasibility and application prospect of our approach. Compared with other CDS engineering efforts, our approach facilitates system development and implementation and improves system maintainability, scalability and efficiency, which contribute to the widespread adoption of effective CDS within the healthcare domain.

Activation of TAS2R4 signaling attenuates podocyte injury induced by high glucose.

Bitter taste receptors (TAS2Rs) Tas2r108 gene possesses a high abundance in mouse kidney; however, the biological functions of Tas2r108 encoded receptor TAS2Rs member 4 (TAS2R4) are still unknown. In the present study, we found that mouse TAS2R4 (mTAS2R4) signaling was inactivated in chronic high glucose-stimulated mouse podocyte cell line MPC, evidenced by the decreased protein expressions of mTAS2R4 and phospholipase C ß2 (PLCß2), a key downstream molecule of mTAS2R4 signaling. Nonetheless, agonism of mTAS2R4 by quinine recovered mTAS2R4 and PLCß2 levels, and increased podocyte cell viability as well as protein expressions of ZO-1 and nephrin, biomarkers of podocyte slit diaphragm, in high glucose-cultured MPC cells. However, blockage of mTAS2R4 signaling with mTAS2R4 blockers γ-aminobutyric acid and abscisic acid, a Gßγ inhibitor Gallein, or a PLCß2 inhibitor U73122 all abolished the effects of quinine on NLRP3 inflammasome and p-NF-κB p65 as well as the functional podocyte proteins in MPC cells in a high glucose condition. Furthermore, knockdown of mTAS2R4 with lentivirus-carrying Tas2r108 shRNA also ablated the effect of quinine on the key molecules of the above inflammatory signalings and podocyte functions in high glucose-cultured MPC cells. In summary, we demonstrated that activation of TAS2R4 signaling alleviated the podocyte injury caused by chronic high glucose, and inhibition of NF-κB p65 and NLRP3 inflammasome mediated the protective effects of TAS2R4 activation on podocytes. Moreover, activation of TAS2R4 signaling could be an important strategy for prevention and treatment of diabetic kidney disease.

Tracking and optimizing toxic chemical exposure pathways through food trade: A case study in SCCPs contaminated seafood in China.

Food safety is related to human health and sustainable development. International food trade poses food safety risks through the collateral transport of toxic chemicals that are detrimental to human health. Domestic interprovincial trade has similar effects within countries but has not been comprehensively investigated previously. Here, we assessed the effects of interprovincial trade on food safety and human dietary exposure to short-chain chlorinated paraffins (SCCPs), a group of emerging persistent toxic chemicals, in seafood across China by synthesizing data from field observation and various models. Our findings indicate that there is a higher level of SCCPs exposure risk in coastal provinces compared to inland provinces. Approximately, 70.3% of human exposure to SCCPs through seafood consumption in China was embodied in the interprovincial seafood trade in 2021. Specifically, the domestic trade led to a remarkable increase in SCCPs exposure in the coastal provinces in South China, attributable to low SCCPs pollution in these provinces and imported seafood from those provinces with high SCCPs pollution. In contrast, human exposure to SCCPs decreased in those coastal provinces in East China due to importing seafood from those provinces with low SCCPs concentrations. The interprovincial seafood trade routes were optimized by linear programming to minimize human exposure to SCCPs considering both shipping cost and health risk constraints. The optimized trade routes reduced the national per capita SCCPs exposure through seafood consumption by over 12%. This study highlights the importance of interprovincial food trade in the risk assessment of toxic chemicals.

Total energy expenditure of 16 Chinese young men measured by the doubly labeled water method.

OBJECTIVE: Doubly labeled water (DLW) method is the gold standard for measuring total energy expenditure (TEE). We used this method to measure TEE in Chinese young men. METHODS: Sixteen healthy young men age 23±1 years with body mass index 22.0±1.4 kg/m2 were recruited. TEE was measured by the DLW method, and basal energy expenditure (BEE) was determined by indirect calorimetry. We also conducted 24-h activity, energy balance and factorial approach to estimate energy requirements of the subjects. RESULTS: TEE of subjects by DLW method was 9.45±0.57 MJ/day (2258±180 kcal/day). The 24-h activity was 10.80±0.33 MJ/day (2582±136 kcal/day). The energy requirement, derived from energy balance observations, was 9.93±1.32 MJ/day (2373±315 kcal/day). The BEE of 6.65±0.28 MJ/day (1589±67 kcal/day), calculated by the adjusted Schofield equation, was significantly higher (P<0.001) than that measured by indirect calorimetry, 5.99±0.66 MJ/day (1433±158 kcal/day). The TEE derived from the factorial approach was 10.31±0.43 MJ/day (2463±104 kcal/day). CONCLUSION: The TEE of Chinese young men measured by the DLW method was about 10% lower than the current recommended nutrient intake (RNI), suggesting that the RNI for Chinese men maybe overestimated. Further studies are warranted to determine the value of the estimated energy requirement.

Evaluation of the protein requirement in Chinese young adults using the indicator amino acid oxidation technique.

OBJECTIVE: To accurately calculate the protein requirements in Chinese young adults using the indicator amino acid oxidation technique. METHODS: Nine women and ten men received a restricted daily level of protein intake (0.75, 0.82, 0.89, 0.97, and 1.05 g/kg), along with L-[1-13C]-leucine. Subjects' protein requirement was determined by a biphasic linear regression crossover analysis of F13CO2 data. In doing so, a breakpoint at the minimal rate of appearance of 13CO2 expiration specific to each level of dietary protein was identified. This trial was registered with the Chinese clinical trial registry as ChiCTR-ONC-11001407. RESULTS: The Estimated Average Requirement (EAR) and the Recommended Nutrient Intake (RNI) of protein for healthy Chinese young adults were determined to be 0.87 and 0.98 g/(kg•d), respectively, based on the indicator amino acid oxidation technique. CONCLUSION: The EAR and RNI of mixed protein are 5% and 16% that are lower than the current proposed EAR and RNI (0.92 and 1.16 g/(kg•d), respectively), as determined by the nitrogen balance method. The respective EAR and RNI recommendations of 0.87 and 0.98 g/(kg•d) of mixed protein are estimated to be reasonable and suitable for Chinese young adults.

[Study on effect and mechanism of volatile oil of schizonepetae herba and its essential components against influenza virus].

OBJECTIVE: To observe the effect of volatile oil of Schizonepetae Herba (VOSH), and its essential components-menthone and pulegone against anti-influenza virus A/PR/8/34 (H1N1) in vivo and in vitro, as well as the signaling mechanism of its toll-like receptor/interferon (TLR/IFN). METHOD: The lung-adapted PR-8 virus model was prepared in mice. They were administered with preventive and therapeutic drugs, and the hemagglutination titer of model animals was determined to evaluate in vivo effect against H1N1. ELISA test was conducted to observe the effect on IFN-alpha, IFN-beta, IL-2, IL-6 and TNF-alpha in serum, as well as IFN-beta secretion in H1N1 infected MDCK supernatant. Real-time RT-PCR was employed to observe the expression levels of IRAK4 and TLR3 mRNA. RESULT: The in vivo experiment shows that the hemagglutination titer was significantly decreased when the mice were treated with VOSH (0.266 mg x kg(-1)), menthone(0.5 mg x kg(-1)) and pulegone (0.19 mg x kg(-1)) in therapeutic way; VOSH (0.226 mg x kg(-1)) had a significant effect on increasing serum levels of IFN-alpha, IL-2; Methone (0.5 mg x kg(-1)) had a significant effect on increasing serum levels of IFN-beta; Methone (0.5 mg x kg(-1)) and pulegone (0.19 mg x kg(-1)) had a significant effect on decreasing serum levels of IL-6; VOSH (0.452, 0.226 mg x kg(-1)) and pulegone (0.19 mg x kg(-1)) had a significant effect on decreasing serum levels TNF-alpha. The in vitro experiment showed that the expression levels of IRAK4 mRNA and IFN-beta were significantly increased in VOHS (0.1 g x L(-1)) and pulegone (0.1 g x L(-1)) groups; and the menthone (0.25 g x L(-1)) group showed a significant rise in the expression levels of IRAK4 mRNA, but a notable decline in TLR3 mRNA. CONCLUSION: The administration with VOSH, methone and pulegone in therapeutic way can significantly decrease the hemagglutination titer, which demonstrates the anti-virus effect of the administration in therapeutic way, but no notable efficacy of the administration in preventive way. The in vivo anti-virus mechanism is related to regulation of IFN-alpha, IFN-beta and IL-2.

Risk factors for medical device-related pressure injury in ICU patients: A systematic review and meta-analysis.

BACKGROUND: Medical device-related pressure injury (MDRPI) in intensive care unit (ICU) patients is a serious issue. We aimed to evaluate the risk factors for MDRPI associated with ICU patients through systematic review and meta-analysis, and provide insights into the clinical prevention of MDRPI. METHODS: We searched PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), WanFang Database, and China BioMedical Literature Database (CBM) (from inception to January 2023) for studies that identified risk factors of MDRPI in ICU patients. In order to avoid the omission of relevant literature, we performed a secondary search of the above database on February 15, 2023. Meta-analysis was performed using Revman 5.3. RESULTS: Fifteen studies involving 4850 participants were selected to analyze risk factors for MDRPI in ICU patients. While conducting a meta-analysis, we used sensitivity analysis to ensure the reliability of the results for cases with significant heterogeneity among studies. When the source of heterogeneity cannot be determined, we only described the risk factor. The risk factors for MDRPI in ICU patients were elder age (OR = 1.06, 95% CI: 1.03-1.10), diabetes mellitus (OR = 3.20, 95% CI: 1.96-5.21), edema (OR = 3.62, 95% CI: 2.31-5.67), lower Braden scale score (OR = 1.22, 95%CI: 1.11-1.33), higher SOFA score (OR = 4.21, 95%CI: 2.38-7.47), higher APACHE II score (OR = 1.38, 95%CI: 1.15-1.64), longer usage time of medical devices (OR = 1.11, 95%CI: 1.05-1.19), use of vasoconstrictors (OR = 6.07, 95%CI: 3.15-11.69), surgery (OR = 4.36, 95% CI: 2.07-9.15), prone position (OR = 24.71, 95% CI: 7.34-83.15), and prone position ventilation (OR = 17.51, 95% CI: 5.86-52.36). Furthermore, we found that ICU patients who used subglottic suction catheters had a higher risk of MDRPI, whereas ICU patients with higher hemoglobin and serum albumin levels had a lower risk of MDRPI. CONCLUSION: This study reported the risk factors for MDRPI in ICU patients. A comprehensive analysis of these risk factors will help to prevent and optimize interventions, thereby minimizing the occurrence of MDRPI.

The effects of paroxetine therapy on depressive symptom and motor function in the treatment of depression with Parkinson's disease: A meta-analysis.

BACKGROUND: Paroxetine therapy has been used for treatment of patients with depression and Parkinson's disease (dPD) in many clinical studies, but, the effects of paroxetine in dPD patients are not completely understood. The aim of this study was to systematically evaluate the effects of paroxetine therapy on depressive symptom and motor function in the treatment of dPD, in order to confer a reference for clinical practice. METHODS: Randomized controlled trials (RCTs) of paroxetine for dPD published up to October, 2022 were retrieved. Standardised mean difference (SMD), odds ratio (OR), and 95% confidence interval (CI) were calculated and heterogeneity was measured with the I2 test. The outcomes of interest were as follows: the efficacy, Hamilton depression rating scale score, unified Parkinson's disease rating scale score, Hamilton anxiety rating scale score or adverse events. RESULTS: Thirty-four RCTs with 2819 participants were included. Compared with control group, the pooled effects of paroxetine therapy on depression were (22 trials; OR 3.62, 95% CI 2.63 to 4.98, P < .00001) for antidepressant response (25 trials; SMD -2.14, 95% CI -2.73 to -1.56, P < .00001) for Hamilton depression rating scale score, the pooled effects of paroxetine therapy on motor function were (10 trials; OR 4.63, 95% CI 3.15 to 6.79, P < .00001) for anti-PD efficacy (18 trials; SMD -2.02, 95% CI -2.48 to -1.55, P < .00001) for total unified Parkinson's disease rating scale score. The Hamilton anxiety rating scale score showed significant decrease in the paroxetine treatment group compared to control group (10 trials; SMD -1.93, 95% CI -2.65 to -1.22, P < .00001). In addition, paroxetine therapy reduced the number of any adverse events obviously in dPD patients (twenty trials; OR 0.42, 95% CI 0.31 to 0.57, P < .00001). CONCLUSIONS: Paroxetine therapy has clinical benefits for improvement of depressive symptom and motor function in dPD patients, moreover, it is of high drug safety. Further well-designed, multi-center RCTs needed to identify these findings.

Lack of miRNA-17 family mediates high glucose-induced PAR-1 upregulation in glomerular mesangial cells.

Upregulation of thrombin receptor protease-activated receptor 1 (PAR-1) is verified to contribute to chronic kidney diseases, including diabetic nephropathy; however, the mechanisms are still unclear. In this study, we investigated the effect of PAR-1 on high glucose-induced proliferation of human glomerular mesangial cells (HMCs), and explored the mechanism of PAR-1 upregulation from alteration of microRNAs. We found that high glucose stimulated proliferation of the mesangial cells whereas PAR-1 inhibition with vorapaxar attenuated the cell proliferation. Moreover, high glucose upregulated PAR-1 in mRNA level and protein expression while did not affect the enzymatic activity of thrombin in HMCs after 48 h culture. Then high glucose induced PAR-1 elevation was likely due to the alteration of the transcription or post-transcriptional processing. It was found that miR-17 family members including miR-17-5p, -20a-5p, and -93-5p were significantly decreased among the eight detected microRNAs only in high glucose-cultured HMCs, but miR-129-5p, miR-181a-5p, and miR-181b-5p were markedly downregulated in both high glucose-cultured HMCs and equivalent osmotic press control compared with normal glucose culture. So miR-20a was selected to confirm the role of miR-17 family on PAR-1 upregulation, finding that miR-20a-5p overexpression reversed the upregulation of PAR-1 in mRNA and protein levels induced by high glucose in HMCs. In summary, our finding indicated that PAR-1 upregulation mediated proliferation of glomerular mesangial cells induced by high glucose, and deficiency of miR-17 family resulted in PAR-1 upregulation.

High glucose upregulates PAR-1 in SH-SY5Y cells via deficiency of miR-20a and miR-190a.

Thrombin activity enhancement and its receptor protease-activated receptor 1 (PAR-1) activation play vital roles in neurologic deficits in the central nervous system. Our recent study showed that PAR-1 upregulation stimulated by chronic high glucose (HG) caused central neuron injury through neuroinflammation; however, the molecular mechanisms are far from clear. In the present study, we found that HG resulted in neuronal injury of SH-SY5Y cells as evidenced by decreased cell viability and increased lactate dehydrogenase release and elevated the mRNA level of PAR-1. Moreover, we predicted and determined several potential microRNAs (miRs) combining with the 3'-UTR of PAR-1 mRNA, finding that miR-20a-5p, miR-93-5p, and miR-190a-5p were significantly decreased in HG-cultured SH-SY5Y cells compared with control. Further, SH-SY5Y cells stably transfected with miR-20a-5p or miR-190a-5p mimic were established, and overexpression efficiency were confirmed. It was found that miR-20a-5p or miR-190a-5p overexpression markedly decreased PAR-1 mRNA level and protein expression in SH-SY5Y cells cultured with HG and normal glucose, indicating that miR-20a or miR-19a deficiency contributed to HG-induced PAR-1 upregulation. Together, our findings demonstrated that PAR-1 upregulation mediated HG-induced neuronal damage in central neurons, which was achieved through miR-20a or miR-190a deficiency.

Piperine, as a TAS2R14 agonist, stimulates the secretion of glucagon-like peptide-1 in the human enteroendocrine cell line Caco-2.

Piperine is reported to ameliorate common metabolic diseases, however, its molecular mechanism is still unclear. In the present study, we examined whether piperine could stimulate glucagon-like peptide-1 (GLP-1) secretion in a human enteroendocrine cell line, Caco-2, and explored the potential mechanisms from the activation of human bitter taste receptors (TAS2Rs). It was found that TAS2R14 was highly expressed in Caco-2 cells, far more than TAS2R4 and TAS2R10. Piperine and flufenamic acid (FA, a known TAS2R14 agonist) markedly increased intracellular calcium mobilization and significantly enhanced the GLP-1 secretion, accompanied by elevated levels of proglucagon mRNA in Caco-2 cells compared with the control. Moreover, piperine and FA activated TAS2R14 signaling as evidenced by the increased mRNA and protein levels of TAS2R14, and the protein expression of its downstream key molecules including phospholipase C ß2 (PLCß2) and a transient receptor potential channel melastatin 5 (TRPM5). On the other hand, a G protein ßγ subunit inhibitor Gallein or a PLC inhibitor U73122 alleviated piperine-stimulated GLP-1 secretion in Caco-2 cells. In the meantime, a flavanone hesperetin significantly attenuated piperine and FA induced the intracellular calcium mobilization and GLP-1 secretion. Furthermore, TAS2R14 knockdown reversed the piperine-triggered up-regulation of PLCß2 and TRPM5 as well as increased the GLP-1 secretion in Caco-2 cells by TAS2R14 shRNA transfection. In summary, our findings demonstrated that piperine promoted the GLP-1 secretion from enteroendocrine cells through the activation of TAS2R14 signaling. Moreover, TAS2R14 was likely a target of piperine in the alleviation of metabolic diseases.

Risk factors for fear of falling in stroke patients: a systematic review and meta-analysis.

OBJECTIVE: Even though 32%-83% for fear of falling (FoF) in patients with stroke, very little is known about the predictors of the problems. Therefore, we systematically reviewed the literature on risk factors for FoF in patients with stroke. DESIGN: A systematic review and meta-analysis DATA SOURCES: PubMed, Embase, Cochrane Library database, Web of Science, CINAHL, PsycINFO, Grey literature and other relevant databases for related publications were searched (from inception to 17 July 2021). RESULTS: Eight studies involving 1597 participants were selected to analyse risk factors for patients with stroke with FoF. The quality of all included studies was assessed and categorised as medium or high quality. Review Manager V.5.3 merged the OR value and 95% CI of the potential risk factors. Meta-regression and Egger's test were performed by Stata V.15.1. The risk factors for FoF in patients with stroke were women (OR=2.13, 95% CI 1.47 to 3.09), impaired balance ability (OR=5.54; 95% CI 3.48 to 8.81), lower mobility (OR=1.12; 95% CI 1.05 to 1.19), history of falls (OR=2.33; 95% CI 1.54 to 3.53) and walking aid (OR=1.98; 95% CI 1.37 to 2.88), anxiety (OR=2.29; 95% CI 1.43 to 3.67), depression (OR=1.80; 95% CI 1.22 to 2.67), poor lower limb motor function (OR=1.14; 95% CI 1.00 to 1.29) and physically inactiveness (OR=2.04; 95% CI 1.01 to 4.12). Measurement of heterogeneity between studies was high for all outcomes (I2 =0%-93%), indicating that the substantial interstudy heterogeneity in estimated proportions was not attributed to the sampling error. Sensitivity analysis (leave-one-out method) showed that the pooled estimate was stable. CONCLUSION: This meta-analysis indicated that female population, impaired balance ability, lower mobility, history of falls and walking aid in patients with stroke might be at greater risk for FoF. Future studies are recommended to determine other risk factors specific to patients with stroke.