Development and validation of matrix metalloproteinase for predicting prognosis and tumour microenvironment immune profiles in uterine corpus endometrial carcinoma.

Background: Matrix metalloproteinases (MMPs) are involved in many processes of tumour progression and invasion. However, few studies have analysed the effects of MMP expression patterns on endometrial cancer (EC) development from the perspective of the tumour microenvironment (TME). we quantified MMP expression in individual by constructing an MMP score and found MMP score effectively predict the prognosis of EC patients. Methods: MMPs expression profiles were determined based on the differential expression of 12 MMP-related regulators. Principal component analysis (PCA) was used to construct an MMP scoring system which can quantify the MMPs expression patterns individually of EC patients. Kaplan-Meier analysis, the log-rank test, and time-dependent receiver operating characteristic (ROC) curve analysis were used to evaluate the value of MMPs expression in predicting prognosis. Single-cell RNA sequencing (scRNA-seq) dataset was used to verify correlation between MMPs and progression of EC. Gene Ontology (GO) analysis was used to investigate the pathways and functions underlying MMPs expression. Tumour immune dysfunction, exclusion prediction, and pharmacotherapy response analyses were performed to assess the potential response to pharmacotherapy based on MMPs patterns. Results: We downloaded the MMPs expression data, somatic mutation data and corresponding clinical information of EC patients from the TCGA website and ICGC portal. Based on the MMP-related differentially expressed genes (DEGs), the MMP score was constructed, and EC patients were divided into high and low MMP score groups. There was a positive correlation between MMP score and prognosis of EC patients. Patients with high MMP scores had better prognosis, more abundant immune cell infiltration and stronger antitumoor immunity. Although prognosis is worse with the lower group than the high, patients with low MMP score had better response to immunotherapy, which means they could prolong the survival time through Immunological checkpoint blockade (ICB) therapy. scRNA-seq analysis identified significant heterogeneity between MMP score and classical pathways in EC. Conclusion: Our work indicates that the MMP score could be a potential tool to evaluate MMP expression patterns, immune cell infiltration, response to pharmacotherapy, clinicopathological features, and survival outcomes in EC. This will provide the more effective guide to select immunotherapeutic strategies of EC in the future.

Applying a Tripodal Hexaurea Receptor for Binding to an Antitumor Drug, Combretastatin-A4 Phosphate.

Phosphates play a crucial role in drug design, but their negative charge and high polarity make the transmembrane transport of phosphate species challenging. This leads to poor bioavailability of phosphate drugs. Combretastatin-A4 phosphate (CA4P) is such an anticancer monoester phosphate compound, but its absorption and clinical applicability are greatly limited. Therefore, developing carrier systems to effectively deliver phosphate drugs like CA4P is essential. Anion receptors have been found to facilitate the transmembrane transport of anions through hydrogen bonding. In this study, we developed a tripodal hexaurea anion receptor (L1) capable of binding anionic CA4P through hydrogen bonding, with a binding constant larger than 104 M-1 in a DMSO/water mixed solvent. L1 demonstrated superior binding ability compared to other common anions, and exhibited negligible cell cytotoxicity, making it a promising candidate for future use as a carrier for drug delivery.

Lactiplantibacillus plantarum ZDY2013 Inhibits the Development of Non-Alcoholic Fatty Liver Disease by Regulating the Intestinal Microbiota and Modulating the PI3K/Akt Pathway.

Non-alcoholic fatty liver disease (NAFLD) is a common chronic hepatic condition whose impact on human health is increasingly significant. The imbalance of the gut microbiome, linked to insulin resistance, heightened intestinal permeability, and pro-inflammatory reactions, may be the linchpin in the development of NAFLD. In our research, the impact of Lactiplantibacillus plantarum ZDY2013 administration for 12 weeks on gut microbiota dysbiosis induced by a high-fat, high-fructose, high-cholesterol (FHHC) diet in male C57BL/6n mice was investigated. Research results presented that the intervention of L. plantarum ZDY2013 in mice fed with the FHHC diet could restore their liver function and regulate oxidative stress. Compared to mice in the model group, the intervention of L. plantarum ZDY2013 significantly regulated the gut microbiota, inhibited the LPS/NF-κB pathway, and led to a lower level of colonic inflammation in the mice administered with L. plantarum ZDY2013. It also improved insulin resistance to regulate the PI3K/Akt pathway and lipid metabolism, thereby resulting in reduced fat accumulation in the liver. The above results suggest that the intervention of L. plantarum ZDY2013 can hinder the progression of diet-induced NAFLD by reducing inflammation to regulate the PI3K/Akt pathway and regulating gut microbiota disturbance.

Changing profiles of the burden of Alzheimer's disease and other dementias attributable to smoking in the belt and road initiative countries: A secondary analysis of global burden of disease 2019.

Objectives: This study was aimed at analyzing the burden and trend of Alzheimer's disease and other dementias attributed to smoking (SADD) in the Belt and Road Initiative (BRI) countries during 1990-2019. Methods: Data from The 2019 Global Burden of Disease Study was used to extract information on the burden of SADD in terms of the numbers and age-standardized rate of mortality (ASMR) and disability-adjusted life years (ASDALR) in the BRI countries for 1990-2019. The average annual percent change (AAPC) was used to analyze the temporal trends of ASDALR from 1990 to 2019 and in the final decade by Joinpoint regression analysis. Results: The DALYs of SADD were the highest in China, India, and the Russian Federation in 1990 and in Lebanon, Montenegro and Bosnia, and Herzegovina in 2019. From 1990 to 2019, the ASDALR in China had increased from 55.50/105 to 66.18/105, but decreased from 2010 to 2019, while that of India had declined from 32.84/105 to 29.35/105, but increased from 2010 to 2019. The ASDALR showed the fastest increase in the Russian Federation, with AAPC of 1.97% (95% confidence interval [CI]: 1.77%, 2.16%), and the fastest decline in Sri Lanka, with AAPC of -2.69% (95% CI: 2.79%, -2.59%). ASMR and ASDALR from SADD showed a substantial decline during 1990-2019 both globally and in the different socio-demographic index (SDI) regions (all P < 0.05, except for the high-middle-SDI region). Compared to the rates in males, the AAPC in ASDALR of females was significantly greater in 20 countries(all P < 0.05). In the age group of 20-54 years, the DALYs rate showed a decreasing trend only in 13 members in the low-SDI region (all P < 0.05). Conclusion: Under the premise of eliminating the differences, mobilizing resources in the country itself, the BRI organization, and globally will help reduce the global SADD burden and achieve healthy and sustainable development.

High level food-grade expression of maltogenic amylase in Bacillus subtilis through dal gene auxotrophic selection marker.

As a food-safe microorganism, Bacillus subtilis has been widely utilized in the production of food enzyme, where a food-grade expression system without antibiotic is required. However, there is no mature system for such expression, since the recombinant plasmid in existing food-grade expression system is unstable especially in high-density fermentation. In this study, we constructed a food-grade expression system based on the dal gene auxotrophic selection marker. Specifically, maltogenic amylase (AmyM) was expressed in dal deletion strain without antibiotic, yielding an activity of 519 U/mL. To increase the expression of AmyM, the promoter of amyM (gene encoding AmyM) was optimized. Furthermore, we found that excessive expression of dal gene was detrimental to the stability of plasmid, and the ribosome binding site (RBS) of dal was mutated with the reduced synthesis of D-alanine. After that, AmyM activity increased to 1364 U/mL with the 100 % stability of plasmid. The 3-L fermentor cultivation was performed with the highest value ever reported in food-grade microorganisms, an activity of 2388 U/mL, showing the scale-up production capability of this system. Besides, it is also able to apply the system for other food enzymes, which indicating the great generalizability of this system for different application.

Burden and trends of stroke attributable to dietary risk factors from 1990 to 2019 in the Belt and Road Initiative countries: an analysis from the global burden of disease study 2019.

Objectives: This study aimed to compare the burden and trends of stroke attributed to dietary risk factors in the Belt and Road ("B&R") countries from 1990 to 2019. Methods: The 2019 Global Burden of Disease (GBD) Study was used to gather information on the burden of stroke attributable to dietary risk factors. Numbers and age-standardized rates (ASRs) of deaths, disability-adjusted life years (DALYs) were determined in 1990 and 2019 among the "B&R" countries. The average annual percent change (AAPC) was used to analyze the temporal trends of diet-induced stroke DALYs from 1990 to 2019 and in the final decade (2010-2019) by Joinpoint regression analysis. Results: In 2019, the absolute number of stroke deaths and DALYs attributable to dietary risk factors were 671,872 cases (95% UI 436,354-937,093) and 1.67 million cases (95% UI 1.15-2.24) in China. We found geographical differences in mortality and DALYs of diet-attributable stroke among member countries, with Bulgaria, Hungary and Serbia being the three highest countries in 1990, Bulgaria, North Macedonia and Montenegro in Central Asia in 2019. The ASRs of diet-induced stroke mortality and DALYs were generally declining in most member states from 1990 to 2019, however, the corresponding metrics in Mongolia remained high. The fastest decline in ASR of mortality and DALYs for diet-induced stroke was seen in Estonia, Eastern Europe, with AAPC values of -7.09% (95%CI: -7.72, -6.46%) and - 6.62% (95%CI: -7.20, -6.03%), respectively. We noted a substantial downward trend in ASR of mortality and DALYs from diet-induced stroke changes in the final decade (2010-2019) for most member states. The ASR of DALYs for diet-induced stroke decreased greater in females than in males. For those aged 50-74, the DALYs for stroke due to dietary risk factors in all other member countries of the "B&R" showed a decreasing trend, except for the Philippines, which rose (AAPC = 2.13, 95%CI: 1.40-2.87%) and Turkmenistan, which remained stable (AAPC = 0.05, 95%CI: -0.43-0.33%). Conclusion: The burden of diet-induced stroke varies substantially across "B&R" countries and threaten public health, relevant evidence-based policies and interventions should be adopted to address the future burden of stroke in "B&R" countries through extensive collaboration.

In Vitro Probiotic Properties of Bifidobacterium animalis subsp. lactis SF and Its Alleviating Effect on Non-Alcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease with many influencing factors. With the increasing role of the gut-liver axis in various liver diseases, research on the prevention and treatment of NAFLD with probiotics is increasing. In the present study, a Bifidobacterium animalis subsp. strain, B. lactis SF, was isolated from the feces of healthy infants and characterized by sequencing of the 16S rDNA. A systematic probiotic evaluation was carried out, and a diet-induced mouse model was constructed to study the effect and mechanism of B. lactis SF on diet-induced NAFLD. Results show that B. lactis SF has excellent gastrointestinal fluid tolerance and intestinal colonization, and strong antibacterial and antioxidant capabilities. In vivo, B. lactis SF modulated intestinal flora, restored the intestinal barrier, and inhibited LPS entrance into the portal circulation, which subsequently inhibited the TLR4/NF-κB and modulated the PI3K-Akt/AMPK signaling pathway, attenuated the inflammatory response, and reduced lipid accumulation. In addition, B. lactis SF attenuated oxidative stress and further alleviated autophagy, resulting in an ameliorative effect on NAFLD. Therefore, our study provides a new dietary method for the treatment of NAFLD.

Antiplatelet effect of ginkgo diterpene lactone meglumine injection in acute ischemic stroke: A randomized, double-blind, placebo-controlled clinical trial.

This study was designed to evaluate antiplatelet effect and therapeutic effect of ginkgo diterpene lactone meglumine injection (GDLI) in acute ischemic stroke (AIS) patients. In this randomized, double-blind, placebo-controlled trial, we randomly assigned 70 inpatients within 48 hr after the onset of AIS to combination therapy with GDLI and aspirin (GDLI at a dose of 25 mg/d for 14 days plus aspirin at a dose of 100 mg/d for 90 days) or to placebo plus aspirin in a ratio of 1:1. Platelet function, the National Institute of Health Stroke Scale (NIHSS), and the modified Rankin Scale (mRS) were evaluated. A good outcome was defined as NIHSS scores decrease ≥5 or mRS scores decrease ≥2. Results showed that arachidonic acid induced maximum platelet aggregation rate (AA-MAR) and mean platelet volume (MPV) of the GDLI-aspirin group were much lower than that of the aspirin group (p = 0.013 and p = 0.034, respectively) after the 14-day therapy. The combination of GDLI and aspirin was superior to aspirin alone, and had significant impact on the good outcome at day 90 (ORadj 7.21 [95%CI, 1.03-50.68], p = 0.047). In summary, GDLI has antiplatelet effect and can improve the prognosis of AIS patients.

Deep white matter hyperintensity is spatially correlated to MRI-visible perivascular spaces in cerebral small vessel disease on 7 Tesla MRI.

BACKGROUND: The association between perivascular space (PVS) and white matter hyperintensity (WMH) has been unclear. Normal-appearing white matter (NAWM) around WMH is also found correlated with the development of focal WMH. This study aims to investigate the topological connections among PVS, deep WMH (dWMH) and NAWM around WMH using 7 Tesla (7T) MRI. METHODS: Thirty-two patients with non-confluent WMHs and 16 subjects without WMHs were recruited from our department and clinic. We compared the PVS burden between patients with and without WMHs using a 5-point scale. Then, the dilatation and the number of PVS within a radius of 1 cm around each dWMH were compared with those of a reference site (without WMH) in the contralateral hemisphere. In this study, we define NAWM as an area within the radius of 1 cm around each dWMH. Furthermore, we assessed the spatial relationship between dWMH and PVS. RESULTS: Higher PVS scores in the centrum semiovale were found in patients with >5 dWMHs (median 3) than subjects without dWMH (median 2, p = 0.014). We found there was a greater dilatation and a higher number of PVS in NAWM around dWMH than at the reference sites (p<0.001, p<0.001). In addition, 79.59% of the dWMHs were spatially connected with PVS. CONCLUSION: dWMH, NAWM surrounding WMH and MRI-visible PVS are spatially correlated in the early stage of cerebral small vessel disease. Future study of WMH and NAWM should not overlook MRI-visible PVS.

Targeting the gut microbiota to investigate the mechanism of Lactiplantibacillus plantarum 1201 in negating colitis aggravated by a high-salt diet.

High-salt diet (HSD) affects the composition and function of the intestinal microbiota and cause health problems. This study confirmed that HSD aggravates dextran sulphate sodium (DSS)-induced colitis by changing the relative abundance of the gut microbiota, activating the NF-κB pathway, and up-regulating the mRNA levels of inflammatory factors. We explored the effect of L. plantarum 1201 in negating DSS-induced ulcerative colitis, which is aggravated by HSD for the first time. Results show that L. plantarum 1201 rebuilt the balance of intestinal flora by decreasing the ratio of Firmicutes/Bacteroidetes and increasing the relative abundance of Bifidobacterium, Lactobacillus and butyric-producing bacteria. Moreover, L. plantarum 1201 inhibited the up-regulation of inflammatory cytokines (e.g., IL-1ß, TNF-α, IL-6, IL-22, and IFN-γ) mRNA levels, increased colonic tight junction protein (ZO-1, ocludin, and claudin-3) expression, and increased serum levels of beneficial metabolites, including alpha-tocopherol (α-T) and D-mannose. By reconstructing an animal model of colitis, we further discovered that α-T and D-mannose inhibited the NF-κB pathway, improved tissue injury, and decreased the expression of pro-inflammatory cytokines (e.g., IL-1ß, TNF-α, and IL-6). This study proves for the first time that L. plantarum 1201 attenuates high-salt-aggravated colitis by increasing the serum concentrations of endogenic D-mannose in mice serum and inhibiting the consumption of α-T through intestinal flora. Therefore, regulating the gut microbiota is a potential treatment for high-salt-aggravated colitis.

Targeted Drug Delivery System Based on Copper Sulfide for Synergistic Near-Infrared Photothermal Therapy/Photodynamic Therapy/Chemotherapy of Triple Negative Breast Cancer.

Multi-modal synergistic therapy, especially the integration of near-infrared laser phototherapies and chemotherapy, is often sought after owing to its minimal invasiveness, low side effects, and improved anticancer therapeutic efficacy. Herein, CuS nanoparticles were first coated with zinc phthalocyanine derivant (Pc)-functionalized mesoporous silica (mSiO2-Pc) to achieve a drug delivery system (CuS@mSiO2-Pc) with photothermal/photodynamic therapy. Chemical drug DOX was subsequently loaded for chemotherapy, and hyaluronic acid (HA) was employed as a covering material with cancer targeting. The as-obtained CuS@mSiO2-Pc(DOX)@HA nanoparticles were nano-sized with good biocompatibility, effective DOX loading, and controllable DOX releasing. Expectedly, this multifunctional nanoplatform exhibits effective generation of reactive oxygen species and hyperthermia upon the near-infrared laser irradiation. Most importantly, the nanoparticles were targeted into 4T1 cells and showed significantly remarkable cytotoxicity under near-infrared laser irradiation, proving their synergistic therapeutic efficacy. Therefore, this targeted drug system based on CuS with synergistic photothermal therapy/photodynamic therapy/chemotherapy has great application prospects in clinical anticancer treatment for triple negative breast cancer.

Prospects of Probiotic Adjuvant Drugs in Clinical Treatment.

In modern society, where new diseases and viruses are constantly emerging, drugs are still the most important means of resistance. However, adverse effects and diminished efficacy remain the leading cause of treatment failure and a major determinant of impaired health-related quality of life for patients. Clinical studies have shown that the disturbance of the gut microbial structure plays a crucial role in the toxic and side effects of drugs. It is well known that probiotics have the ability to maintain the balance of intestinal microecology, which implies their potential as an adjunct to prevent and alleviate the adverse reactions of drugs and to make medicines play a better role. In addition, in the past decade, probiotics have been found to have excellent prevention and alleviation effects in drug toxicity side effects, such as liver injury. In this review, we summarize the development history of probiotics, discuss the impact on drug side effects of probiotics, and propose the underlying mechanisms. Probiotics will be a new star in the world of complementary medicine.

Longitudinal analysis of ovarian cancer death patterns during a rapid transition period (2005-2020) in Shanghai, China: A population-based study.

Objectives: It is important to assess the burden of ovarian cancer related premature death so as to develop appropriate evidence-based care and improve women's health. This study aimed to characterize the long-term trends in mortality, survival and disease burden of ovarian cancer in Shanghai, China. Materials and Methods: Co-morbidities, crude mortality rate (CMR), age-standardised mortality rate by Segi's world standard population (ASMRW), years of life lost (YLL), and survival rates were analysed. Temporal trends for the mortality rates and disease burden were analyzed using the Joinpoint Regression Program. Mortality rate increases by demographic and non-demographic factors were estimated by the decomposition method. Results: A total of 1088 ovarian cancer as underlying cause of deaths were recorded. CMR and ASMRW were 4.82/105 and 2.32/105 person-years, respectively. The YLL was 16372.96 years, and the YLL rate was 72.46/105 person-years. The YLL rate increased only in the age group of 70-79 years (P = 0.017). The survival rates of ovarian cancer patients did not improve during the ten year period (2005-2015). The top co-morbidities were diseases of the respiratory system, digestive system, and circulatory system. The rates of ovarian cancer deaths caused by non-demographic and demographic factors increased by 21.29% (95%CI: 4.01% to 41.44%, P = 0.018) and 25.23% (95%CI: 14.64% to 36.81%, P < 0.001), respectively. Conclusions: Population ageing and all cause of death may affect ovarian cancer related deaths in Pudong, Shanghai. The high mortality and the stagnant survival rates suggest the need for more efforts in targeted prevention and treatment of this disease.

Effect of Bifidobacterium animalis subsp. lactis SF on enhancing the tumor suppression of irinotecan by regulating the intestinal flora.

The gut microbiota plays a role in tumor therapy by participating in immune regulation. Here, we demonstrated through 8-day probiotic supplementation experiments and fecal microbiota transplantation experiments that Bifidobacterium animalis subsp. lactis SF enhanced the antitumor effect of irinotecan and prevented the occurrence of intestinal damage by modulating the gut microbiota and reducing the relative abundance of pro-inflammatory microbiota. Therefore, the intestinal inflammation was inhibited, the TGF-ß leakage was reduced, and the PI3K/AKT pathway activation was inhibited. Thus, the tumor apoptotic autophagy was finally promoted. Simultaneously, the reduction of TGF-ß relieved the immunosuppression caused by CPT-11, promoted the differentiation of CD4+ and CD8+ T cells in tumor tissue, and consequently inhibited tumor growth and invasion. This study disclosed the mechanism of B. lactis SF assisting CPT-11 in antitumor activity and suggested that B. lactis SF plays a new role in anticancer effects as a nutritional intervention.

Day to Day Blood Pressure Variability Associated With Cerebral Arterial Dilation and White Matter Hyperintensity.

BACKGROUND: Previous studies suggested blood pressure variability (BPV) might help reveal interactions between blood pressure fluctuation and white matter lesions, and the impact of elevated BPV on white matter hyperintensity (WMH) or cerebral arterial dilation is unclear. METHODS: This retrospective observational study involved 2634 stroke-free individuals (68.6±11.1 years, 50.3% female), who underwent magnetic resonance imaging and magnetic resonance angiography scans, from a single center in Shanghai, China. Measurements for variability of blood pressure were made based on 7 days blood pressure recordings. WMHs were quantified from T2-FLAIR images and further classified as periventricular WMH or deep WMH. M1 segment of middle cerebral artery dilation was assessed from magnetic resonance angiography images. General linear model was used to examine the associations. RESULTS: Both increased systolic and diastolic BPV were associated with increased WMH volume (systolic: ß=0.02 [95% CI, 0.004-0.03], P=0.01; diastolic: ß=0.05 [95% CI, 0.03-0.08], P<0.001). Only periventricular WMH was associated with BPV (systolic: ß=0.02 [95% CI, 0.005-0.04], P=0.01; diastolic: ß=0.06 [95% CI, 0.04-0.09], P<0.001). MCA dilation was found in 125 individuals (4.75%). Systolic BPV was associated with MCA dilation only in the hypertensive individuals (ß=0.11 [95% CI, 0.06-0.17], P<0.001). Increased WMH volume was found associated with dilated MCA (ß=0.17 [95% CI, 0.11-0.23], P<0.001). CONCLUSIONS: Increased BPV might be one of the pathophysiological phenomena involving in the small vessel disease independent of hypertension. Increased BPV might independently contribute to intracranial arterial dilation. Management of BPV might be a target to preserve cerebrovascular wellness.

Passivating the pH-Responsive Sites to Configure a Widely pH-Stable Emulsifier for High-Efficiency Benzyl Alcohol Oxidation.

Widely pH-stable emulsions configured by solid emulsifiers with high chemical stabilities and anti-corrosion properties under strong acid or alkaline conditions are highly sought after for practical and wide application of Pickering interfacial catalysis. Herein, a unique strategy was reported for synthesis of a widely pH-stable and novel emulsifier by passivating the pH-responsive sites on graphene oxide nanoribbon (GONR) surface using ionic liquid (IL). The suitable wettability of GONR-IL was derived from the positive binding energy between IL and water, which ensured the stability of the emulsion in a wide pH range. Benefiting from the passivated surface chemistry of GONR, the emulsion microreactor stabilized by GONR-IL exhibited a remarkable stability over a wide range of pH values. A GONR-IL-supported Pd catalyst stabilized at the toluene-water interface achieved an excellent emulsion catalytic activity for benzyl alcohol oxidation (conversion of 92 %), which was exceedingly higher than that of Pd/GONR (<1 %), Pd/CNTs-IL (51 %), or Pd/GO-IL (8 %).

High On-Treatment Platelet Reactivity as Predictor of Long-term Clinical Outcomes in Stroke Patients with Antiplatelet Agents.

The purpose was to explore the value of high on-treatment platelet reactivity (HTPR) in predicting long-term clinical outcomes for stroke patients. The platelet reactivity was assayed after being treated with either 75 mg clopidogrel or 100 mg aspirin daily with VerifyNow System in stroke patients. HTPR for clopidogrel was defined as PRU ≥ 208, and that for aspirin was defined as ARU ≥ 550. CYP2C19 genotyping was performed using the Sequenom MassARRAY iPLEX platform. The primary endpoint was a composite of recurrent ischemic stroke, transient ischemic attack, myocardial infarction, or ischemic vascular death. The safety endpoint was bleeding. In the clopidogrel group, among 345 patients recruited, 174 of them were categorized as HTPR. A total of 270 patients were followed up for 54 months. There was a significant association between HTPR and the primary endpoint (HRadj 2.13 [95% CI, 1.43-3.15], p < 0.001). Among the 314 participants genotyped for CYP2C19, 187 (59.6%) were classified as CYP2C19 loss-of-function allele carriers. Patients with at least 1 loss-of-function allele were more likely to present with HTPR (ORadj 2.61 [95%CI, 1.43-4.77], p = 0.008), and had a higher risk of the primary endpoint (HRadj 2.05 [95% CI, 1.30, 3.25], p = 0.002). In the aspirin group, among 140 patients recruited, 28 of them were categorized as HTPR. A total of 121 patients were followed up for 30 months. Similarly, there was a significant association between HTPR and the primary endpoint (HRadj 3.28 [95% CI, 1.52-7.71], p = 0.002). HTPR is an independent risk factor for ischemic events during long-term follow-up in stroke patients. Platelet function testing is helpful to evaluate the effect of antiplatelet therapy for stroke patients.

Protective Effect of Lactiplantibacillus plantarum 1201 Combined with Galactooligosaccharide on Carbon Tetrachloride-Induced Acute Liver Injury in Mice.

Acute liver injury (ALI) has a high mortality rate of approximately 20-40%, and it is imperative to find complementary and alternative drugs for treating ALI. A carbon tetrachloride (CCl4)-induced ALI mouse model was established to explore whether dietary intervention can alleviate ALI in mice. Intestinal flora, intestinal integrity, biomarkers of hepatic function, systemic inflammation, autophagy, and apoptosis signals were detected through a real-time PCR, hematoxylin-eosin staining, 16S rRNA gene sequencing, and so on. The results showed that Lactiplantibacillus plantarum 1201 had a strongly antioxidant ability, and galactooligosaccharide (GOS) could boost its growth. Based on these findings, the combination of L. plantarum 1201 and GOS, the synbiotic, was applied to prevent CCl4-induced ALI in mice. The current research proved that GOS promoted the intestinal colonization of L. plantarum 1201, and the synbiotic improved the antioxidant capacity of the host, regulated the intestinal flora, repaired the intestinal barrier, inhibited the activation of the MAPK/NF-κB pathway, and then inhibited the apoptosis and autophagy pathways, relieving inflammation and liver oxidation; thereby, the ALI of mice was alleviated. These results suggest that synbiotics may become a new research direction for liver-protecting drugs.

Years of Life Lost Due to Premature Death and Their Trends in People With Selected Neurological Disorders in Shanghai, China, 1995-2018: A Population-Based Study.

Background: Neurological disorders are the leading cause of long-term disability and the second leading cause of death in the world. We aimed to characterize the long-term trends in mortality and disease burden of selected neurological disorders and quantitatively analyze the contributions of demographic and non-demographic factors on the mortality of selected neurological disorders in Shanghai, China, 1995-2018. Methods: Mortality data were derived from the Vital Statistics System of Pudong New Area, Shanghai, China, during 1995-2018. Temporal trends for the mortality rates and burden of selected neurological disorders were analyzed by Joinpoint Regression Program. Years of life lost (YLL) was used to analyze the burden of disease. The increasing mortality rates related to demographic and non-demographic factors were estimated by the decomposition method. Results: A total of 4432 deaths from selected neurological disorders occurred during 1995-2018, accounting for 0.98% of total deaths. The crude mortality rates (CMR) and age-standardized mortality rates (ASMRW) of neurological disorders were 7.14/105 person-years and 4.08/105 person-years, respectively. Extrapyramidal and movement disorders, other degenerative diseases of the nervous system, and episodic and paroxysmal disorders were the three leading causes of mortality and YLL of selected neurological disorders. The CMR, ASMRW, and rate of YLL for deaths from selected neurological disorders showed significantly increasing trends in males, females, and the total population during 1995-2018 (all P < 0.001). The contribution rates of increased values of CMR related to demographic factors were more evident than non-demographic factors. Conclusion: The mortality rate and rate of YLL for death from selected neurological disorders increased significantly during 1995-2018 in Pudong New Area, Shanghai. The demographic factors, particularly aging, might be related to an increase in the mortality of neurological disorders. More effective prevention strategies are needed to prevent the aging-related death and burden from neurological disorders in the future.

Lactiplantibacillus plantarum 1201 Inhibits Intestinal Infection of Salmonella enterica subsp. enterica Serovar Typhimurium Strain ATCC 13311 in Mice with High-Fat Diet.

Salmonella Typhimurium is widely distributed in food. It can colonise the gastrointestinal tract after ingestion, causing lamina propria edema, inflammatory cell infiltration, and mucosal epithelial decomposition. A high-fat diet (HFD) can induce an inflammatory response, but whether HFD can increase the infection level of S. Typhimurium is unknown. We established a model of Salmonella enterica subsp. enterica serovar Typhimurium strain ATCC 13311 ATCC 13311 infection in healthy adult mice with a maintenance diet (MD) or HFD to explore the effect of Lactiplantibacillus plantarum 1201 intervention on S. Typhimurium ATCC 13311 colonization and its protective effects on mice. HFD exacerbated the infection of S. Typhimurium ATCC 13311, while the intervention of L. plantarum 1201 effectively mitigated this process. L. plantarum 1201 can reduce the colonies of S. ATCC 13311 in the intestines and tissues; and reduce intestinal inflammation by down-regulating the level of TLR4/NF-κB pathway related proteins in serum and the expression of related inflammatory factors in the colon and jejunum. Since L. plantarum 1201 can inhibit the colonization of S. Typhimurium ATCC 13311 and relieve inflammation in HFD, current research may support the use of L. plantarum 1201 to prevent S. Typhimurium infection.