[Rules of acupoint selection and pattern-acupoint relationship in treatment with acupuncture and moxibustion for endometriosis based on complex network analysis technology].

OBJECTIVE: To explore the rules of acupoint selection and pattern-acupoint relationship in treatment with acupuncture and moxibustion for endometriosis (EMs) based on complex network analysis technology. METHODS: The articles for clinical trial of EMs treated with acupuncture and moxibustion were searched from CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase and Cochrane Library from the inception of the databases to December 14, 2022. Using Microsoft Excel 2019 software, the database was established to collect the use frequency of acupoint, meridian tropism, location and pattern-acupoint relationship. SPSS Modeler 18.0 Apriori algorithm was adopted to conduct the association rule analysis, Cytoscape3.7.2 software was used to plot the complex co-occurrence network map; and SPSS Statistics 26.0 was adopted to perform hierarchical cluster analysis on high-frequency acupoints and a tree diagram was drawn. RESULTS: A total of 163 articles were included, and 167 core acupoint prescriptions and 74 pattern-associated acupoint prescriptions were extracted, involving 92 acupoints, with a cumulative frequency of 1 223 times. The top five acupoints with the highest use frequency were Guanyuan (CV 4), Sanyinjiao (SP 6), Zhongji (CV 3), Zigong (EX-CA 1) and Qihai (CV 6). The selected acupoints were mostly distributed in the chest, abdomen and lower limbs; and the involved meridians included the conception vessel, the spleen meridian of foot-taiyin and the stomach meridian of foot-yangming. The acupoint compatibility of high frequency referred to Guanyuan (CV 4) - Sanyinjiao (SP 6), Guanyuan (CV 4) - Zhongji (CV 3), and Guanyuan (CV 4) - Zigong (EX-CA 1). The close association was presented among Guanyuan (CV 4), Sanyinjiao (SP 6), Qihai (CV 6) and Zhongji (CV 3), which had the strongest connection with the other acupoints; among the top 25 acupoints with the highest use frequency, 5 acupoint prescriptions with high frequency were obtained by the cluster analysis. Guanyuan (CV 4), Qihai (CV 6), Sanyinjiao (SP 6), Zigong (EX-CA 1) and Zhongji (CV 3) were selected for cold and blood stagnation; Guanyuan (CV 4), Sanyinjiao (SP 6), Zhongji (CV 3), Dahe (KI 12) and Taixi (KI 3) for kidney deficiency and blood stagnation; Zhongji (CV 3), Guanyuan (CV 4), Sanyinjiao (SP 6), Xuehai (SP 10) and Diji (SP 8) for qi and blood stagnation; Qihai (CV 6), Guanyuan (CV 4), Zusanli (ST 36), Xuehai (SP 10), and Zigong (EX-CA 1) for qi deficiency and blood stagnation; Sanyinjiao (SP 6), Fenglong (ST 40), Zhongliao (BL 33), Ciliao (BL 32) and Xialiao (BL 34) for interaction of phlegm and stasis; and Daheng (SP 15), Guanyuan (CV 4), Zhongji (CV 3), Qihai (CV 6) and Zhongwan (CV 12) for retention of damp and heat. CONCLUSION: The core acupoints are Guanyuan (CV 4), Sanyinjiao (SP 6), Zhongji (CV 3), Qihai (CV 6) and Zigong (EX-CA 1) in treatment of endometriosis with acupuncture and moxibustion. Six patterns/syndromes are involved in clinical practice. In terms of the properties, functions and indications, the supplementary acupoints are selected on the basis of the core acupoints for different patterns/sydnromes of the disease.

Adverse Drug Events Observed with the Newly Approved Remimazolam in Comparison to Propofol for General Anesthesia in Patients Undergoing Surgery: A Meta-analysis.

INTRODUCTION: Developments in anesthetic pharmacology have been aiming at minimizing physiological disturbance in addition to maintaining and improving titrateability, recovery profile, and patient experience. Remimazolam, a GABAAlpha receptor agonist, is a new intravenous anesthetic agent which has recently been approved for use. This analysis aimed to systematically compare the adverse drug events reported with the newly approved remimazolam in comparison to propofol for general anesthesia (GA) in patients undergoing surgery. METHODS: Electronic databases were searched from 15 May to 20 December 2023 for relevant publications which compared the outcomes reported with the newly approved remimazolam versus propofol in patients undergoing surgery. Relevant reported adverse drug events were the endpoints of this study. The statistical analysis was carried out using the latest version of the RevMan software. Data analysis was represented by risk ratio (RR) with 95% confidence intervals (CI). RESULTS: Sixteen studies with a total number of 1897 participants were included in this analysis; 1104 participants received remimazolam and 793 participants received propofol. The risks for hypotension (RR 0.50, 95% CI 0.43-0.58; P = 0.00001), hypoxemia (RR 0.43, 95% CI 0.19-0.99; P = 0.05), bradycardia (RR 0.53, 95% CI 0.36-0.78; P = 0.001), pain at injection site (RR 0.07, 95% CI 0.01-0.56; P = 0.01), and total adverse events (RR 0.33, 95% CI 0.24-0.47; P = 0.00001) were significantly lower with remimazolam. However, no significant differences were observed in terms of postoperative nausea and vomiting (RR 0.98, 95% CI 0.66-1.46; P = 0.93), dizziness (RR 0.42, 95% CI 0.11-1.57; P = 0.20), psychiatric symptoms (RR 1.09, 95% CI 0.45-2.67; P = 0.85), and respiratory depression (RR 0.81, 95% CI 0.24-2.76; P = 0.74). CONCLUSION: Our current analysis showed that the newly approved remimazolam was apparently associated with significantly fewer adverse drug events in comparison to propofol for GA in patients undergoing surgery. Therefore, this new drug should be further studied and more research with larger population sizes should be carried out to confirm this hypothesis.

Anti-aging Factor GRSF1 Attenuates Cerebral Ischemia-Reperfusion Injury in Mice by Inhibiting GPX4-Mediated Ferroptosis.

Abnormal accumulation of senescent cells in tissues has been shown to facilitate the onset and progression of various diseases. As an important protein involving in the regulation of cellular senescence process, researches suggested GRSF1 as a potential senolytic target to improve multiple physiological and pathological processes. However, the underlying mechanism of cellular senescence on cerebral ischemia-reperfusion injury (CIRI) has not been revealed. Here, we investigated the effect of GRSF1 on CIRI and delved into its specific mechanisms. In the present study, we established a mouse model of cerebral ischemia-reperfusion (CIR) and observed low expression of anti-aging factor GRSF1, along with greatly increased levels of senescence-related markers p16 and p21 and senescence-associated secretory phenotype TNF-α. Furthermore, we found that the expression of GPX4 was elevated parallel to GRSF1 in CIR mice with overexpression of GRSF1, oxidative stress, and iron metabolism-related proteins were inhibited. Functionally, overexpressing GRSF1 significantly ameliorated infarct volume and neurological function scores and suppressed apoptosis in CIR mice, while administration of GPX4 inhibitors reversed these beneficial phenotypes. Taken together, our results indicate cellular senescence as an important pathological mechanism to exacerbate cerebral injury during CIRI, while GRSF1 could inhibit oxidative stress-mediated ferroptosis through upregulating GPX4 to attenuate reperfusion injury, which makes senolytic treatment, especially GRSF1, a promising therapeutic target for CIRI.

Peptidoglycan biosynthesis-associated enzymatic kinetic characteristics and ß-lactam antibiotic inhibitory effects of different Streptococcus pneumoniae penicillin-binding proteins.

Penicillin-binding proteins (PBPs) include transpeptidases, carboxypeptidases, and endopeptidases for biosynthesis of peptidoglycans in the cell wall to maintain bacterial morphology and survival in the environment. Streptococcus pneumoniae expresses six PBPs, but their enzymatic kinetic characteristics and inhibitory effects on different ß-lactam antibiotics remain poorly understood. In this study, all the six recombinant PBPs of S. pneumoniae displayed transpeptidase activity with different substrate affinities (Km = 1.56-9.11 mM) in a concentration-dependent manner, and rPBP3 showed a greater catalytic efficiency (Kcat = 2.38 s-1) than the other rPBPs (Kcat = 3.20-7.49 × 10-2 s-1). However, only rPBP3 was identified as a carboxypeptidase (Km = 8.57 mM and Kcat = 2.57 s-1). None of the rPBPs exhibited endopeptidase activity. Penicillin and cefotaxime inhibited the transpeptidase and carboxypeptidase activity of all the rPBPs but imipenem did not inhibited the enzymatic activities of rPBP3. Except for the lack of binding of imipenem to rPBP3, penicillin, cefotaxime, and imipenem bound to all the other rPBPs (KD = 3.71-9.35 × 10-4 M). Sublethal concentrations of penicillin, cefotaxime, and imipenem induced a decrease of pneumococcal pbps-mRNA levels (p < 0.05). These results indicated that all six PBPs of S. pneumoniae are transpeptidases, while only PBP3 is a carboxypeptidase. Imipenem has no inhibitory effect on pneumococcal PBP3. The pneumococcal genes for encoding endopeptidases remain to be determined.

A meta-analysis of randomized controlled trials comparing enteral immunonutrition (EIN) and standard enteral nutrition regarding biochemical, immunological, and clinical outcomes in gastrectomy patients with gastric cancer and investigating evidence networks for EIN formulae.

Introduction: For patients with gastric cancer who have undergone gastrectomy, recent research has shown that enteral immunonutrition (EIN) is more successful than enteral nutrition (EN) at boosting host immunity and, in turn, improving prognosis. The claimed outcomes, however, are inconsistent. Aim: This meta-analysis examines how EIN affects biochemical, immunological, and clinical outcomes for gastrectomy (GC) patients following gastrectomy and EIN formulae evidence networks. Material and methods: A comprehensive search of the Medline, EMBASE, Scopus, and Cochrane Library databases identified English-language peer-reviewed journal papers. The odds ratio (OR) and standard mean difference (SMD) were calculated, along with their 95% confidence intervals. The heterogeneity was assessed using Cochrane Q and I2 statistics and the appropriate p-value. The analysis used RevMan 5.3. Results: This meta-analysis included 10 RCTs involving 1409 GC patients, 714 of whom were assigned to EIN and 695 to EN. After EIN treatment, serum proalbumin, serum transferrin, lymphocyte count, and CD4+/CD8+ ratio had statistically significant standardised mean differences (SMDs) of 2.39, 2.39, 1.34, and 0.72, respectively. EIN reduces postoperative infectious complications with an OR of 0.63 (95% CI: 0.41-0.77) for infections, an OR of 0.63 for complications, and an SMD of -1.05 for systemic inflammations. A network diagram with high-quality data and a well-defined network design with consistent and accurate connection shows that EIN can improve serum protein levels, immunological parameters, and post-operative problems. Conclusions: The use of EIN has been shown to enhance cellular immunity, regulate inflammatory response, and decrease postoperative complications in GC patients who underwent major GI surgery.

OK-432 Sclerotherapy of Giant Cervicomediastinal Cystic Hygroma.

Cystic hygroma is one type of the benign malformations and typically located in the neck, clavicle, and others, in children under the age of 5 years. However, the incidence of giant cervicomediastinal giant cystic hygroma is very rare, especially in adulthood. Such a location and age make its diagnosis difficult because they are usually asymptomatic. Complete surgical resection seems impossible while multiple sites are involved. Herein, we present a case of giant cervicomediastinal cystic hygroma, describing the clinical presentation, radiographic features, and OK-432 sclerotherapy. In conclusion, repeated OK-432 sclerotherapy may be an effective treatment option in giant cervicomediastinal cystic hygroma. Pay close attention to patient's symptoms and vital signs, adjusting the OK-432 dose throughout the process.

Molecular Characterization of Predominant Serotypes, Drug Resistance, and Virulence Genes of Streptococcus pneumoniae Isolates From East China.

Streptococcus pneumoniae is a common diplococcus pathogen found worldwide. The characterization of predominant serotypes, drug resistance, and virulence genes of S. pneumoniae isolates prevailing in different areas and countries is clinically important for choice of antibiotics and improvement of vaccines. In this study, pneumonia (78.7%) and meningitis (37.0%) were the predominant diseases observed in the 282 (children) and 27 (adults) S. pneumoniae-infected patients (p < 0.05) from seven hospitals in different areas of East China. Of the 309 pneumococcal isolates, 90.3% were classified by PCR into 15 serotypes, with serotypes 19F (27.2%) and the 6A/B (19.1%) being most predominant (p < 0.05). Importantly, serotypes 15A and 15B/C combined for a total of 10.4% of the isolates, but these serotypes are not included in the 13-valent pneumococcal capsule conjugate vaccine used in China. Antimicrobial susceptibility analysis by the E-test showed that >95% of the 309 pneumococcal isolates were susceptible to moxifloxacin and levofloxacin, as well as 18.4, 85.8, and 81.6% of the isolates displayed susceptibility to penicillin, cefotaxime, and imipenem, respectively. A significant correlation between the prevalence of predominant serotypes and their penicillin resistance was observed (p < 0.05). In particular, >95% of all the pneumococcal isolates showed resistance to erythromycin and azithromycin. Of the nine detected virulence genes, the lytA, ply, hysA, and nanA were the most common with 95-100% positive rates in the 309 pneumococcal isolates, while the pavA and psaA genes displayed a significant correlation with pneumococcal bacteremia and meningitis (p < 0.05). Overall, our data suggested that the predominant serotypes, drug resistance, and virulence genes of the S. pneumoniae isolates prevailing in East China are distinct from those observed in other areas of China and adjacent countries.

Efficacy of systematic voice training combined with swallowing function exercises for the prevention of swallowing dysfunction in stroke patients: a retrospective study.

Background: Stroke is a common clinical brain disease, and swallowing dysfunction is one of the most common complications in stroke patients. Despite multiple treatments for swallowing dysfunction, it often leads to a series of complications. Interventions such as systematic voice training and swallowing function exercises have emerged in recent years, but their effectiveness remains unclear. Therefore, this study was conducted to investigate the effect of systematic voice training combined with swallowing function exercise for the prevention of swallowing dysfunction and improving the quality of life of stroke patients. Methods: We retrospectively analyzed 90 stroke patients admitted to Baotou Central Hospital from October 2018 to October 2021 as study subjects, and divided the patients into a combined voice training group (n=45) and a single swallowing exercise group (n=45) according to the interventions. The single swallowing exercise group received routine swallowing function exercise, and the combined voice training group used systematic voice training combined with swallowing function exercise. The incidence of swallowing dysfunction, malnutrition, aspiration pneumonia, and exercise compliance rate were compared between the two groups, and the quality of life of the two groups was evaluated by the Generic Quality of Life Inventory 74 (GQOLI-74) before and after the interventions, respectively. Results: The incidence of swallowing dysfunction, aspiration pneumonia, and malnutrition were lower in the combined voice training group than in the single swallowing exercise group (P<0.05), and there was no statistically significant difference in the exercise compliance rate between the two groups. The combined voice training group had higher psychological dimensions, physical dimensions, social adaptation, and total quality of life scores than the single swallowing exercise group (all P<0.05). Compared with the conventional intervention group, the combined voice training group had higher patient satisfaction (P<0.05). Conclusions: Systematic voice training combined with swallowing function exercise can effectively prevent the occurrence of swallowing dysfunction and improve the quality of life of patients with stroke.

Genetic Effects of the Schizophrenia-Related Gene DTNBP1 in Temporal Lobe Epilepsy.

Recent studies have reported patients who concurrently exhibit conditions of epilepsy and schizophrenia, indicating certain shared pathologies between them. This study aimed to investigate the genetic effects of the schizophrenia-related gene DTNBP1 in temporal lobe epilepsy (TLE). A total of 496 TLE patients and 528 healthy individuals were successfully genotyped for six DTNBP1 polymorphisms (rs760665, rs1011313, rs2619528, rs2619522, rs909706, and rs2619538), including 335 TLE patients and 325 healthy controls in cohort 1, and 161 TLE patients and 203 healthy controls in cohort 2. The frequency of the TT genotype at rs909706 T > C was lower in TLE patients than in normal controls in the initial cohort (cohort 1), which was confirmed in an independent cohort (cohort 2). However, the intronic T allele failed to be in linkage disequilibrium (LD) with any functional variations nearby; thus, together with the CCAC and TCAT haplotypes (rs1011313-rs2619528-rs2619522-rs909706) observed in the study, this allele acts only as a protective factor against susceptibility to TLE. Meanwhile, a novo mutant allele rs2619538 T > A was exclusively observed in TLE patients, and a dual-luciferase assay revealed that the mutant allele was increased by approximately 22% in the DTNBP2 promoter compared with the wild-type allele. Together with the trend of increasing DTNBP1 expression in epilepsy patients and animal models in this study, these are the first findings to demonstrate the genetic association of DTNBP1 with TLE. Homozygous mutation of rs2619538 T > A likely promotes DTNBP1 expression and facilitates subsequent processes in epilepsy pathologies. Thus, the role of DTNBP1 in TLE deserves further exploration in the future.

Intranasal Delivery of miR-155-5p Antagomir Alleviates Acute Seizures Likely by Inhibiting Hippocampal Inflammation.

INTRODUCTION: To confront the resistance to existing antiepileptic drugs, studies have gradually begun to investigate alternative pathologies distinct from the traditional treatments that overwhelmingly target ion channels. Microglia activation is the first inflammatory response in the brain, in which miR-155-5p plays a key proinflammatory role and thus represents a promising target for inflammatory modulation in epilepsy pathologies. METHODS: In this study, a pentetrazol-induced acute seizure model was established, and the seizure degree was evaluated within 60 min after pentetrazol administration. Animals were then sacrificed for hippocampal tissue collection for biological experiments. RESULTS: Intranasal delivery of miR-155-5p antagomir (30 min before pentetrazol administration) increased the percentage of animals with no induced seizures by 20%, extended the latency to generalized convulsions, and decreased seizure severity. In addition, miR-155-5p antagomir treatment alleviated hippocampal damage and decreased the expression of typical inflammatory modulators (TNF-α, IL-1ß and IL-6). Further research revealed that intranasal delivery of miR-155-5p antagomir significantly decreased the relative level of miR-155-5p and increased the expression of its targets LXRα and SOCS1 in IBA1-labeled microglial cells in the hippocampus. CONCLUSION: These findings demonstrate that intranasal delivery of miR-155-5p antagomir alleviated acute seizures, likely by blocking hippocampal inflammation. However, other potential mechanisms of the effects of miR-155-5p antagomir and its long-term safety for epilepsy treatment remain to be investigated.

The Regulatory Role of Long Noncoding RNAs in Different Brain Cell Types Involved in Ischemic Stroke.

Stroke results in high morbidity and high mortality worldwide, with ischemic stroke accounting for 80% to 85%. As effective treatments for ischemic stroke remain limited because of the narrow therapeutic time window, a better understanding of the pathologic mechanism and new therapeutic intervention targets are needed. Due to the development of next-generation sequencing technologies and the genome-wide analysis of eukaryotic transcriptomes, a large amount of evidence to date demonstrates that long noncoding RNAs (lncRNAs) play a vital role in gene regulation and in ischemic stroke. In recent years, many studies have been focused on the clinical significance of lncRNAs in ischemic stroke, and data shows that the pathological processes underlying ischemic stroke are driven by interactions among different brain cell types, including neurons, glial cells, and vascular cells, which actively participate in the mechanisms of tissue injury and repair. In this mini review article, we provide an overview of the characteristics and underlying regulation mechanisms of lncRNAs relevant to different brain cell types during the course of ischemic stroke. Moreover, we reveal the roles of lncRNAs as potential biomarkers and treatment targets in ischemic stroke.