Development and validation of a nomogram for predicting pulmonary infections after Intracerebral hemorrhage in elderly people.

OBJECTIVES: The purpose of this study was to develop and validate a nomogram for the prediction of pulmonary infections in elderly patients with intracerebral hemorrhage (ICH) during hospitalization in the intensive care unit (ICU). METHODS: A total of 1183 elderly patients diagnosed with ICH were included from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database and randomly grouped into training (n=831) and validation (n=352) cohorts. Candidate predictors were identified using the least absolute shrinkage and selection operator (LASSO) regression. Meanwhile, the variables derived from the LASSO regression were included in the multivariate logistic regression analysis, the variables with P < 0.05 were included in the final model and the nomogram was constructed. The discriminatory ability was assessed by plotting the receiver operating curve (ROC) and calculating the area under the curve (AUC). The Performance of the model was assessed by calibration plots and the Hosmer-Lemeshow goodness-of-fit test (HL test). In addition, clinical decision curves assess the net clinical benefit. RESULTS: The nomogram included chronic lung disease, dysphagia, mechanical ventilation, use of antibiotics, Glasgow Coma Scale (GCS), Logical Organ Dysfunction System (LODS), blood oxygen saturation (SpO2), white blood cell count (WBC) and prothrombin time (PT). The AUC of the predictive model was 0.905 (95 % CI: 0.877, 0.764) in the training cohort and 0.888 (95 % CI: 0.754, 0.838) in the validation cohort, which showed satisfactory discriminative ability. Second, the nomogram showed good calibration. Decision curve analysis showed that the predictive nomogram was clinically useful. CONCLUSION: A prediction model for predicting pulmonary infections in elderly ICH patients was constructed. The model can help clinicians to identify high-risk patients as soon as possible and prevent the occurrence of pulmonary infections.

Emerging High-Level Tigecycline Resistance: Novel Tetracycline Destructases Spread via the Mobile Tet(X).

Antibiotic resistance in bacteria has become a great threat to global public health. Tigecycline is a next-generation tetracycline that is the final line of defense against severe infections by pan-drug-resistant bacterial pathogens. Unfortunately, this last-resort antibiotic has been challenged by the recent emergence of the mobile Tet(X) orthologs that can confer high-level tigecycline resistance. As it is reviewed here, these novel tetracycline destructases represent a growing threat to the next-generation tetracyclines, and a basic framework for understanding the molecular epidemiology and resistance mechanisms of them is presented. However, further large-scale epidemiological and functional studies are urgently needed to better understand the prevalence and dissemination of these newly discovered Tet(X) orthologs among Gram-negative bacteria in both human and veterinary medicine.

ISKpn40-Mediated Mobilization of the Colistin Resistance Gene mcr-3.11 in Escherichia coli.

The mobile colistin resistance gene mcr-3 has globally disseminated since it was first reported in 2017 in Escherichia coliIn vitro mobilization assays in this study demonstrate the functionality of the composite transposon structure ISKpn40-mcr-3.11-dgkA-ISKpn40 in wild-type and recA-E. coli strains. These transpositions generated 4-bp duplications at the target sites. This is the first report demonstrating the mobility of the mcr-3.11 gene by transposition.

Global clonal spread of mcr-3-carrying MDR ST34 Salmonella enterica serotype Typhimurium and monophasic 1,4,[5],12:i:- variants from clinical isolates.

OBJECTIVES: To investigate the prevalence and transmission of mcr-3 among Salmonella enterica serotype Typhimurium and 1,4,[5],12:i:-. METHODS: A total of 4724 clinical Salmonella isolates were screened for the presence of mcr-3 in China during 2014-19. The clonal relationship of the mcr-3-positive isolates and their plasmid contents and complete sequence were also characterized based on WGS data from the Illumina and MinION platforms. RESULTS: We identified 10 mcr-3-positive isolates, and all were MDR, mostly resistant to colistin, cefotaxime, ciprofloxacin, doxycycline and florfenicol. mcr-3 was co-present with blaCTX-M-55-qnrS1 on hybrid ST3-IncC-FII conjugatable plasmids (n = 6) and an ST3-IncC non-conjugatable plasmid (n = 1) and embedded into a pCHL5009T-like IncFII plasmid on the Salmonella chromosome (n = 3). Four distinctive genetic contexts surrounded mcr-3 and all but one were closely related to each other and to the corresponding region of IncFII plasmid pCHL5009T. IS15DI was most likely the vehicle for integration of mcr-3-carrying IncFII plasmids into ST3-IncC plasmids and the chromosome and for shaping the MDR regions. In addition, a phylogenetic tree based on the core genome revealed a unique Salmonella lineage (≤665 SNPs) that contained these 10 mcr-3-positive isolates and another 38 (33 from patients) mcr-3-positive Salmonella from five countries. In particular, most of the 51 mcr-3-positive isolates belonged to ST34 and harboured diverse antibiotic resistance genes (ARGs), including mcr-3-blaCTX-M-55-qnrS1, and possessed similar ARG profiles. CONCLUSIONS: Our findings revealed global clonal spread of MDR ST34 Salmonella from clinical isolates co-harbouring mcr-3 with blaCTX-M-55 and qnrS1 and a flexibility of mcr-3 co-transmittance with other ARGs mediated by mobile genetic elements.

High Genetic Plasticity in Multidrug-Resistant Sequence Type 3-IncHI2 Plasmids Revealed by Sequence Comparison and Phylogenetic Analysis.

We report a novel fusion plasmid, pP2-3T, cointegrating sequence type 3 (ST3)-IncHI2 with an IncFII plasmid backbone mediating multidrug resistance (MDR) and virulence. Phylogenetic analysis and comparative genomics revealed that pP2-3T and other MDR ST3-IncHI2 plasmids clustered together, representing a unique IncHI2 lineage that exhibited high conservation in backbones of plasmids but possessed highly genetic plasticity in various regions by acquiring numerous antibiotic resistance genes and fusing with other plasmids. Surveillance studies should be performed to monitor multiresistance IncHI2 plasmids among Enterobacteriaceae.

A novel SLC6A8 mutation associated with intellectual disabilities in a Chinese family exhibiting creatine transporter deficiency: case report.

BACKGROUND: X-linked creatine transporter deficiency (OMIM#300036,CRTR-D) is characterized by cerebral creatine deficiency, intellectual disabilities, severe speech impairment, seizures and behavioral problems. Mutations in the creatine transporter gene SLC6A8, a member of the solute-carrier family 6 mapped to Xq28, have been reported to cause the creatine transporter deficiency. CASE PRESENTATION: The proband presented at 5 yrs. 1 month of age with delays in intellectual and development, seizures and behavioral problems. A novel missense mutation, c.1181C > A (p.Thr394Lys), in the SLC6A8 gene (NM_005629.3) was detected via targeted exome sequencing, and then validated by Sanger sequencing. Multiple in silico variant effect analysis methods, including SIFT, PolyPhen2, PROVEAN, and Mutation Taster predicted that this variant was likely damaging or diseasing-causing. This hemizygous variation was also identified in the affected brother with the same clinical condition and inherited from the heterozygous carrier mother. The diagnosis was suggested by increased urinary creatine/creatinine (Cr:Crn) ratio and markedly reduced creatine content peak by brain proton magnetic resonance spectroscopy (MRS). The proband's mother became pregnant with a 3rd sibling, in whom the Sanger sequencing result of c.1181C > A was negative. CONCLUSION: The novel mutation c.1181C > A in the SLC6A8 gene reported in a Chinese family has expanded the mutation spectrum of CRTR-D. The combination of powerful new technologies such as targeted exome sequencing with thorough systematic clinical evaluation of patients will improve the diagnostic yield, and assist in genetic counselling and prenatal diagnosis for suspected genetic disorders.

Complete Nucleotide Sequence of an IncI2 Plasmid Coharboring blaCTX-M-55 and mcr-1.

We report the complete nucleotide sequence of a plasmid, pA31-12, carrying blaCTX-M-55 and mcr-1 from a chicken Escherichia coli isolate. pA31-12 has an IncI2 replicon that displays extensive sequence similarity with pHN1122-1-borne blaCTX-M-55 and pHNSHP45-borne mcr-1 Insertion sequences ISEcp1 and ISApl1 are responsible for the mobilization of blaCTX-M-55 and mcr-1, respectively. The colocalization of mcr-1 with an extended-spectrum ß-lactamase gene on a conjugative plasmid may accelerate the dissemination of both genes by coselection.

Visual analysis of acupuncture point selection patterns and related mechanisms in acupuncture for hypertension.

BACKGROUND: Hypertension has become one of the most pathogenic diseases in the world. OBJECTIVE: This paper summarizes and analyzes the acupuncture point combinations and treatment principles of acupuncture for hypertension in a systematic way by means of big data mining. METHODS: The literature for this paper was obtained from CNKI, Wanfang, VIP, SinoMed and PubMed, Embase, Cochrane Library, Web of Science, and Ovid databases. Thedata were collected to obtain combinations of acupoints with strong associations through association rule analysis, complex networks for screening to obtain core acupoint nuclei, and cluster analysis to derive treatment principles. RESULTS: A total of 127 acupuncture prescriptions involving 66 acupoints were included in this study. Tai-chong (LR3), Qu-chi (LI11), Zu-san-li (ST36), Feng-chi (GB20), and He-gu (LI4) were the most commonly used acupoints. The large intestine meridian was the preferred meridian, and most of the extremity acupoints, especially the lower extremities, were selected clinically. The association rule reveals that Qu-chi (LI11) and Zu-san-li (ST36) are the dominant combination acupoints. 3 core association points obtained after complex network analysis, the 1st association, Bai-hui (DU20), Tai-xi (KI3), Gan-shu (BL18), Shen-shu (BL23); The 2nd association, Qu-chi (LI11), He-gu (LI4), San-yin-jiao (SP6), Zu-san-li (ST36), Feng-chi (GB20), Tai-chong (LR3); The 3rd association, Qi-hai (RN6), Guan-yuan (RN4), Zhong-wan (RN12), Zhao-hai (KI6), Tai-yang (EX-HN5), Lie-que (LU7), Yang-ling-quan (GB34), Xing-jian (LR2), Yin-ling-quan (SP9). Cluster analysis yielded the treatment principles of nourishing Yin and submerging Yang, pacifying the liver and submerging Yang, tonifying Qi and Blood, and calming the mind and restoring the pulse, improving clinical outcomes. CONCLUSION: By means of big data mining, we can provide reference for acupuncture point grouping and selection for clinical acupuncture treatment of hypertension.

Molecular characteristic of mcr-1 gene in Escherichia coli from aquatic products in Guangdong, China.

OBJECTIVES: Aquatic ecosystems serve as a dissemination pathway and a reservoir of both antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs). This study aimed to determine the prevalence of colistin-resistant mcr-like genes in Enterobacteriales in aquatic products, which may be contribute to the transfer of ARGs in water environments. METHODS: The mcr-1-positive Escherichia coli were recovered from 123 freshwater fish and 34 cultured crocodile cecum samples from 10 farmers' markets in Guangdong, China. Minimum inhibitory concentration (MIC) was determined using the agar dilution method. Genotyping was performed using pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST). Conjugation assay was carried out to investigate the transferability of mcr-1. Genomic information was obtained by whole genome sequencing (WGS) and bioinformatic analysis. RESULTS: Forty-four mcr-1 positive isolates showed co-resistance to tetracycline, trimethoprim/sulfamethoxazole, and gentamicin, while they were all sensitive to tigecycline, meropenem, and amikacin. They were typed into sixteen PFGE clusters. ST10 and ST117 were the most popular sequence types, followed by ST1114. S1-PFGE verified the presence of the mcr-1 gene on plasmids in sizes of ∼60 kb (n = 1) and ∼240 kb (n = 3). Whole genome sequencing-based analysis identified mcr-1 integrated in IncHI2 plasmid (n = 3), IncI2 plasmid (n = 2), and bacterial chromosome in two copies (n = 1). In addition to mcr-1, they carried several other antibiotic resistance genes, such as blaCTX-M-14, fosA3, and aac(6')-Ib-cr. CONCLUSION: These data suggest that aquatic products are an important antibiotic resistance reservoir and highlight possible risks regarding food safety.

Stroke Phase Is Essential for Pneumonia in Dysphagia Patients After Cerebral Infarction.

BACKGROUND: The risk of pneumonia increases after stroke, especially in poststroke dysphagia patients. Propensity score matching (PSM) is a statistical method in SPSS, which can be used to balance the difference between the 2 groups of known factors. Nasogastric tube feeding is an important factor of stroke-associated pneumonia. However, few studies have used PSM to eliminate the effect of confounding factor. METHODS: Our research was a retrospective case-control study. Retrospective review of the patient database between December 1, 2019, and June 30, 2022, to identify consecutive dysphagia patients after cerebral infarction during hospitalization. An 1:1 PSM in SPSS 25.0 was used to balance nasogastric tube feeding between patients with and without pneumonia. The characteristics of these 2 groups were analyzed. Univariate and binary logistic regression analyses were used to screen the risk factors of dysphagia after cerebral infarction. RESULTS: After 1:1 PSM, 198 subjects met our criteria and were included in the analysis. Age [odds ratio (OR)=1.047, 95% CI: 1.013-1.081, P =0.006], stroke phase (acute stroke) (OR=5.931, 95% CI: 1.133-31.054, P =0.035), admission National Institutes of Health Stroke Scale score (OR=1.058, 95% CI: 1.004-1.115, P =0.034), and length of hospital stay (OR=1.025, 95% CI: 1.001-1.049, P =0.042) had statistically significant correlation with pneumonia in patients with dysphagia after cerebral infarction. CONCLUSION: In clinical practice, for the prevention of pneumonia in patients with dysphagia after cerebral infarction, we should pay more attention to admission National Institutes of Health Stroke Scale score, age, and stroke phase, especially in acute cerebral infarction patients.

Research Note: Pharmacokinetics of bromhexine hydrochloride in broilers after single oral and intravenous administration.

The current study aimed to investigate the pharmacokinetics of bromhexine hydrochloride in broilers after single intravenous (IV) and oral (PO) administration at 2.5 mg/kg body weight (BW). The trial adopted a randomized, parallel-controlled design, where 20 twelve-wk-old broilers were randomly assigned to either the PO or IV group. Blood samples were collected at predetermined time points, and plasma was further separated for analysis. The bromhexine hydrochloride concentrations in plasma samples were determined using an ultra-performance liquid chromatography-tandem quadrupole mass spectrometry (UPLC-MS/MS) method. Noncompartmental analysis (NCA) using Phoenix software was conducted to analyze the concentration versus time data of bromhexine hydrochloride in every chicken. Subsequently, the main pharmacokinetic parameters between the 2 groups were statistically analyzed using SPSS software. Results from NCA revealed that after oral administration at 2.5 mg/kg BW, bromhexine hydrochloride exhibited slow absorption, reaching an average peak concentration of 32.72 ng/mL at 1.78 h. However, incomplete absorption was observed, with an absolute bioavailability of only 20.06% ± 10.84%. Additionally, bromhexine hydrochloride displayed wide distribution, with a steady-state distribution volume (VSS) of 22.55 ± 13.45 L/kg, and slow elimination, with a clearance (Cl) of 1.52 ± 0.38 L/h/kg. Furthermore, gender effects were assessed on the pharmacokinetics of bromhexine hydrochloride in broilers, revealing better absorption in male broilers compared to females. This disparity may be attributed to the faster blood flow and richer blood volume typically found in male broilers.

Comparison of gamithromycin residue depletion in yellow-feather and white-feather broilers after one single subcutaneous injection.

This study aimed to compare the residue depletion of gamithromycin in yellow-feather and white-feather broilers, using Sanhuang and Arbor Acres chickens as typical examples, respectively. Each breed (54 chickens) received a single subcutaneous dose of gamithromycin at 7.5 mg/kg bodyweight (BW). Tissues, including muscle, skin + fat, liver, kidney, and injection site, were collected at 6 h, 3, 5, 7, 10, 14, 21, 28, and 35 d postdrug administration. Gamithromycin concentrations in these tissues were determined using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The kinetics of gamithromycin were analyzed in different tissues using a noncompartmental method in the Phoenix software. Differences were observed in gamithromycin concentrations and kinetic characteristics in both breeds of chickens, with higher residue concentrations and longer residue times found in yellow-feathered broilers. In Sanhuang broilers, the elimination rates of gamithromycin followed this order: injection site > muscle > liver > kidney > skin + fat. The corresponding elimination half-lives (t1/2λzs) in these samples were 1.22, 1.30, 1.71, 2.04, and 2.52 d, respectively. In contrast, in Arbor Acres broilers, a different order was noted: muscle > injection site > kidney > liver > skin + fat, with corresponding t1/2λzs of 1, 1.23, 1.88, 1.93, and 2.21 d, respectively. These differences may be related to variations in pigments in various tissues of chickens of the 2 breeds. However, further investigations are warranted to discern the underlying reasons.

Effects of chitooligosaccharide on the in vitro antibacterial activity against avian Escherichia coli and the pharmacokinetics of florfenicol in healthy chickens.

This study investigates the combined effects of chitooligosaccharide (COS) and florfenicol (FLO) on the inhibition of Escherichia coli in vitro, as well as the pharmacokinetic interactions between these compounds in healthy chickens. The minimum inhibitory concentration (MIC) of COS and FLO alone and the fractional inhibitory concentration index (FICI) after combined treatment were determined using the broth microdilution method and checkerboard method, respectively. Additionally, we evaluated the pharmacokinetic interactions between the 2 types of COS and FLO in healthy chickens. Thirty chickens were randomly divided into 3 groups: Florfenicol group (30 mg/kg), COS J85 group (COS J85 20 mg/kg + florfenicol 30 mg/kg), COS H85 group (COS H85 20 mg/kg + florfenicol 30 mg/kg). Either FLO or COS was orally administered by gavage. The concentrations of FLO in chicken plasma were measured at different time points after the drug withdrawal using high-performance liquid chromatography (HPLC), and pharmacokinetic parameters were calculated by a compartmental method. The results showed that COS J85 and COS H85, when combined with FLO, had FICI values of 0.1875 to 0.75 and 0.3125 to 1, respectively, indicating good synergistic or additive effects against Escherichia coli. The pharmacokinetics of FLO alone and in combination with COS followed a 1-compartment model with first-order absorption and elimination. Furthermore, the pharmacokinetic analysis revealed that the elimination half-life (t1/2ke) of florfenicol was significantly increased in the COS H85 group compared to oral administration of florfenicol alone (P < 0.05). Other pharmacokinetic parameters did not show significant changes (P > 0.05), except between the 2 combined treatment groups, where statistical differences were observed for various parameters, excluding the area under the concentration-time curve from the time of dosing to infinity (AUC) and peak concentration (Cmax).

Preparation of a novel antibacterial magnesium carbonate coating on a titanium surface and its in vitro biocompatibility.

Magnesium-based coatings have attracted great attention in surface modification of titanium implants due to their superior angiogenic and osteogenic properties. However, their biological effects as a carbonate-based constituent remain unrevealed. In this study, magnesium carbonate coatings were prepared on titanium surfaces under hydrothermal conditions and subsequently treated with hydrogen peroxide. Also, their antibacterial activity and in vitro cell biocompatibility were evaluated. The obtained coatings consisted of nanoparticles without cracks and exhibited excellent adhesion to the substrate. X-ray diffraction (XRD) results indicated pure magnesium carbonate coatings formed on the Ti surface after hydrothermal treatment. After hydrogen peroxide treatment, the phase composition of the coatings had no obvious change. Compared to the untreated coatings, the hydrogen peroxide-treated coatings showed increased surface roughness and hydrophilicity. Co-culture with Staphylococcus aureus (S. aureus) demonstrated that the obtained coatings had good antibacterial activity. In vitro cell culture results showed that the hydrogen peroxide-treated coatings enhanced the viability, proliferation, and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). These findings suggest that this MgCO3-based coating exhibits excellent antibacterial performance and osteogenic potential. Based on the above, this study provides a simple method for preparing titanium implants with dual antibacterial and osteogenic capabilities, holding great promise in clinical applications.

Tackling Antibiotic Resistance: Exploring 5-Fluorouracil as a Promising Antimicrobial Strategy for the Treatment of Streptococcus suis Infection.

Streptococcus suis (S. suis) is a zoonotic pathogen with a global distribution, which causes serious diseases in both humans and animals and economic losses in the swine industry. As antibiotic resistance increases, there is an urgent imperative to explore novel antibacterial alternatives. In the present study, we selected the anticancer drug 5-fluorouracil (5-FU) approved by the Food and Drug Administration (FDA) as a candidate drug to treat S. suis infections. The results showed that various pathogens, especially S. suis, are more sensitive to 5-FU. Moreover, the cytotoxicity of 5-FU is relatively low. Extensive in vitro assays demonstrated the pronounced bacteriostatic and bactericidal efficacy of 5-FU against susceptible and multidrug-resistant S. suis strains. Its mechanisms of action include damage to the bacterial cell walls and membranes, resulting in the leakage of intracellular components, and the inhibition of thymidylate synthase (TS), leading to a depletion of deoxythymidine triphosphate (dTTP) pools, ultimately causing thymine-less death and lethal DNA damage in bacteria. Gene-knockout experiments further showed that 5-FU played a role by inhibiting the thyA gene-encoding thymidine synthase. Finally, we determined that S. suis infections can be alleviated by 5-FU in the mouse infection model. This study emphasizes the antibacterial potential of 5-FU against S. suis and provides evidence for its targeting of bacterial membrane damage and DNA damage. In summary, 5-FU can control S. suis infection and is expected to become a new alternative to antibiotics.

Evaluation of natural ageing responses on Burmese amber durability by FTIR spectroscopy with PLSR and ANN models.

Amber ageing is an inevitable process, which is very important in precious organic gemstone relics protection. In order to explore the mechanism of amber ageing and estimate the durability of Burmese amber, this research investigates the changing spectral features of Burmese ageing amber via Fourier Transform Infrared Spectroscopy (FTIR) and solid 13C Nuclear Magnetic Resonance spectroscopy (NMR) and develops the regression models for its micro-hardness by micro-FTIR spectra. The Partial Least Squares Regression (PLSR) and Artificial Neural Networks (ANN) methods as well as Competitive Adaptive Reweighted Sampling (CARS) algorithm for wavelength variables selection have been applied to predict and assess the Vickers hardness of amber samples with different ageing degrees. As a result, the FTIR and the solid 13C NMR spectra reveal that the contents of CO groups (of esters) increase substantially, and which of the other oxygenic groups (CO (of acids), COC, COCC) increase modestly in amber ageing. When comparing with the results of four different models (PLSR, ANN, CARS-PLSR and CARS-ANN), the CARS-PLSR model obtained the optimal results as follows: the squared correlation coefficient of calibration(R2cal) is 0.9230 and the root mean square error of calibration (RMSEC) is 1.2977 HV; the squared correlation coefficient of prediction (R2pre) is 0.7762 and the root mean square error of prediction (RMSEP) is 2.2208 HV. The overall results sufficiently demonstrate that FTIR spectroscopy technique coupled with appropriate chemometrics methods are very promising tools to estimate and predict the hardness property of Burmese ageing amber.

Comparative efficacy and safety of multiple acupuncture therapies for post stroke cognitive impairment: a network meta-analysis of randomized controlled trials.

Background: Acupuncture therapy has been widely used to treat post-stroke cognitive impairment (PSCI). However, acupuncture therapy includes multiple forms. Which acupuncture therapy provides the best treatment outcome for patients with PSCI remains controversial. Objective: We aimed to compare and evaluate the efficacy and safety of different acupuncture-related therapies for PSCI in an attempt to identify the best acupuncture therapies that can improve cognitive function and self-care in daily life for patients with PSCI, and bring new insights to clinical practice. Method: We searched eight databases including PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, China Biomedical Literature Database (CBM), China Science and Technology Journal (VIP) database, China National Knowledge Infrastructure (CNKI) database, and Wan fang database to find randomized controlled trials (RCTs) of acupuncture-related therapies for PSCI from the inception of the database to January 2023. Two researchers independently assessed the risk of bias in the included studies and extracted the study data. Pairwise meta-analyzes for direct comparisons were performed using Rev. Man 5.4 software. Bayesian network meta-analysis (NMA) was performed using STATA 17.0 and R4.2.4 software. The quality of evidence from the included studies was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. Adverse effects (AEs) associated with acupuncture therapy were collected by reading the full text of the included studies to assess the safety of acupuncture therapy. Results: A total of 62 RCTs (3 three-arm trials and 59 two-arm trials) involving 5,073 participants were included in this study. In the paired meta-analysis, most acupuncture-related therapies had a positive effect on cognitive function and self-care of daily living in patients with PSCI compared with cognitive training. Bayesian NMA results suggested that ophthalmic acupuncture plus cognitive training (79.7%) was the best acupuncture therapy for improving MMSE scores, with scalp acupuncture plus cognitive training ranking as the second (73.7%). The MoCA results suggested that warm acupuncture plus cognitive training (86.5%) was the best acupuncture therapy. In terms of improvement in daily living self-care, scalp acupuncture plus body acupuncture (87.5%) was the best acupuncture therapy for improving MBI scores. The most common minor AEs included subcutaneous hematoma, dizziness, sleepiness, and pallor. Conclusion: According to our Bayesian NMA results, ophthalmic acupuncture plus cognitive training and warm acupuncture plus cognitive training were the most effective acupuncture treatments for improving cognitive function, while scalp acupuncture plus body acupuncture was the best acupuncture treatment for improving the performance of self-care in daily life in patients with PSCI. No serious adverse effects were found in the included studies, and acupuncture treatment appears to be safe and reliable. However, due to the low methodological quality of the included studies, our findings need to be treated with caution. High-quality studies are urgently needed to validate our findings. Systematic review registration: https://www.crd.york.ac.uk/prospero/#recordDetails, identifier: CRD42022378353.

Methyl anthranilate deteriorates biofilm structure of Streptococcus suis and antagonizes the capsular polysaccharide defence effect.

BACKGROUND: Streptococcus suis is an important zoonotic pathogen that often causes biofilm-associated infection. Bacterial biofilm-dependent infection is associated with enhanced drug resistance, making it difficult to eradicate. Novel therapeutic approaches are required urgently to treat infections associated with S. suis biofilm. This study aimed to investigate the effects and mechanisms of methyl anthranilate (MA) on S. suis biofilm. METHODS: The effect of MA on S. suis biofilm was determined using the crystal violet method, and the microstructure of the biofilm was observed by electron microscopy. The effects on capsular polysaccharides were determined using the phenol-sulphuric acid method and high-performance liquid chromatography. Adhesion and antiphagocytosis properties of S. suis were detected via cell assays. Molecular docking, molecular dynamics simulation and enzyme activity inhibition assays were used to further explore the effect of MA on AI-2 quorum sensing (QS) of S. suis. Finally, the therapeutic effect of MA was investigated using a mouse infection model. RESULTS: MA destroyed the structure of S. suis biofilm, hindered biofilm formation, and reduced the synthesis of capsular polysaccharides significantly, which further weakened the adhesion and antiphagocytosis ability of S. suis. MA had a docking effect and binding site (SER76 and ASP197) similar to S-adenosylhomocysteine (SAH). Further analysis showed that MA competitively bound 5'-methyladenosine/S-adenosine homocysteine nucleosidase with SAH to interfere with AI-2 QS. In a mouse model, MA reduced the bacterial burden and inflammatory infiltrates effectively. CONCLUSION: This study revealed the antibiofilm effects of MA, and highlighted its potential as a QS inhibitor against S. suis infection.

Acupuncture treatment vs. cognitive rehabilitation for post-stroke cognitive impairment: A systematic review and meta-analysis of randomized controlled trials.

Background: Cognitive impairment is one of the common sequelae after stroke, which not only hinders the recovery of patients but also increases the financial burden on families. In the absence of effective therapeutic measures, acupuncture treatment has been widely used in China to treat post-stroke cognitive impairment (PSCI), but the specific efficacy is unclear. Therefore, this review aimed to evaluate the true efficacy of acupuncture treatment in patients with PSCI. Methods: We searched eight databases [PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, China Biomedical Literature Database (CBM), China Science and Technology Journal (VIP) database, the China National Knowledge Infrastructure (CNKI) database, and Wan fang database] from the inception to May 2022 for randomized controlled trials (RCTs) related to acupuncture treatment combined with cognitive rehabilitation (CR) for PSCI. Two investigators independently used a pre-designed form to extract valid data from eligible RCTs. The risk of bias was assessed through tools provided by the Cochrane Collaboration. The meta-analysis was implemented through Rev Man software (version 5.4). The strength of the evidence obtained was evaluated using GRADE profiler software. Adverse events (AEs) were collected by reading the full text and used to evaluate the safety of acupuncture treatment. Results: Thirty-eight studies involving a total of 2,971 participants were included in this meta-analysis. Overall, the RCTs included in this meta-analysis were poor in methodological quality. The combined results showed that acupuncture treatment combined with CR showed significant superiority compared to CR alone in terms of improving cognitive function [Mean Difference (MD) = 3.94, 95% confidence intervals (CI): 3.16-4.72, P < 0.00001 (MMSE); MD = 3.30, 95%CI: 2.53-4.07, P < 0.00001 (MoCA); MD = 9.53, 95%CI: 5.61-13.45, P < 0.00001 (LOTCA)]. Furthermore, the combination of acupuncture treatment and CR significantly improved patients' self-care ability compared to CR alone [MD = 8.66, 95%CI: 5.85-11.47, P < 0.00001 (MBI); MD = 5.24, 95%CI: 3.90-6.57, P < 0.00001 (FIM)]. Meanwhile, subgroup analysis showed that MMSE scores were not sufficiently improved in the comparison of electro-acupuncture combined with CR versus CR alone (MD = 4.07, 95%CI: -0.45-8.60, P = 0.08). However, we also observed that electro-acupuncture combined with CR was superior to the use of CR alone in improving MoCA and MBI scores in patients with PSCI [MD = 2.17, 95%CI: 0.65-3.70, P = 0.005 (MoCA); MD = 1.74, 95%CI: 0.13-3.35, P = 0.03 (MBI)]. There was no significant difference in the occurrence of adverse events (AE) between acupuncture treatment combined with CR and CR alone (P > 0.05). The certainty of the evidence was rated low level because of flaws in the study design and considerable heterogeneity among the included studies. Conclusion: This review found that acupuncture treatment combined with CR may have a positive effect on improving cognitive function and self-care ability in PSCI patients. However, our findings should be treated with caution owing to the existence of methodological quality issues. High-quality studies are urgently required to validate our results in the future. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022338905, identifier: CRD42022338905.