Targeting ferroptosis for treatment of Alzheimer' s disease / 中国药理学通报

Alzheimer' s disease (AD) is a progressive neurodegenerative disorder histologically characterized by the presence of senile plaques and neurofibrillary tangles (NFTs) found in and around pyramidal neurons in cortical tissue. Mounting evidence suggests regional increased iron load and dyshomeostasis have been associated with oxidative stress, oxidation of proteins and lipids, and cell death, and appears to be a risk factor for more rapid cognitive decline, thereby involved in multiple aspects of the pathophysiology of AD. Ferroptosis is a newly identified iron-dependent lipid peroxidation-driven cell death and emerging evidences have demonstrated the involvement of ferroptosis in the pathological process of AD. Notably, some novel compounds targeting ferroptosis can relieve AD-related pathological symptoms in AD cells and animal model and exhibit potential clinical benefits in AD patients. This review systematically summarizes the growing molecular and clinical evidence implicating ferroptosis in the pathogenesis of AD, and then reviews the application of ferroptosis inhibitors in mouse/cell models to provide valuable information for future treatment and prevention of AD.

Clinical management and prognosis for descending necrotizing mediastinitis / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the clinical characteristics, treatment experiences and prognostic factors for descending necrotizing mediastinitis (DNM). Methods: A retrospective analysis was performed on the data of 22 patients with DNM diagnosed and treated in Henan Provincial People's Hospital from January 2016 to August 2022, including 16 males and 6 females, aged 29-79 years. After admission, all patients underwent CT scanning of the maxillofacial, cervical, and thoracic regions to confirm their diagnoses. Emergency incision and drainage were performed. The neck incision was treated with continuous vacuum sealing drainage. According to the prognoses, the patients were divided into cure group and death group, and the prognostic factors were analyzed. SPSS 25.0 software was used to analyze the clinical data. Rusults: The main complaints were dysphagia (45.5%, 10/22) and dyspnea (50.0%, 11/22). Odontogenic infection accounted for 45.5% (10/22) and oropharyngeal infection accounted for 54.5% (12/22). There were 16 cases in the cured group and 6 cases in the death group, with a total mortality rate of 27.3%. The mortality rates of DNM typeⅠand typeⅡwere respectively 16.7% and 40%. Compared with the cured group, the death group had higher incidences for diabetes, coronary heart disease and septic shock (all P<0.05). There were statistically significant differences between the cure group and the death group in procalcitonin level (50.43 (137.64) ng/ml vs 2.92 (6.33) ng/ml, M(IQR), Z=3.023, P<0.05) and acute physiology and chronic health evaluation Ⅱ(APACHEⅡ) score (16.10±2.40 vs 6.75±3.19, t=6.524, P<0.05). Conclution: DNM is rare, with high mortality, high incidence of septic shock, and the increased procalcitonin level and APACHE Ⅱ score combined diabetes and coronary heart disease are the poor prognostic factors for DNM. Early incision and drainage combined with continuous vacuum sealing drainage technique is a better way to treat DNM.

Phenotype-genotype analysis of the autosomal recessive hereditary hearing loss caused by OTOA variations / 中华耳鼻咽喉头颈外科杂志

Objective: To analyze the phenotypic-genotypic characteristics of hereditary deafness caused by OTOA gene variations. Methods: Family histories, clinical phenotypes and gene variations of six pedigrees were analyzed, which were diagnosed with hearing loss caused by OTOA gene variations at the PLA General Hospital from September 2015 to January 2022. The sequence variations were verified by Sanger sequencing and the copy number variations were validated by multiplex ligation-dependent probe amplification (MLPA) in the family members. Results: The hearing loss phenotype caused by OTOA variations ranged from mild to moderate in the low frequencies, and from moderate to severe in the high frequencies in the probands, which came from six sporadic pedigrees, among which a proband was diagnosed as congenital deafness and five were diagnosed as postlingual deafness. One proband carried homozygous variations and five probands carried compound heterozygous variations in OTOA gene. Nine pathogenic variations (six copy number variations, two deletion variations and one missense variation) and two variations with uncertain significance in OTOA were identified in total, including six copy number variations and five single nucleotide variants, and three of the five single nucleotide variants were firstly reported [c.1265G>T(p.Gly422Val),c.1534delG(p.Ala513Leufs*11) and c.3292C>T(p.Gln1098fs*)]. Conclusions: OTOA gene variations can lead to autosomal recessive nonsyndromic hearing loss. In this study, the hearing loss caused by OTOA defects mostly presents as bilateral, symmetrical, and postlingual, and that of a few presents as congenital. The pathogenic variations of OTOA gene are mainly copy number variations followed by deletion variations and missense variations.

Quality analysis of surgical specimens of rectal cancer in the Chinese taTME registry coll-aborative database: a nationwide registered study / 中华消化外科杂志

Objective:To analyze the quality of surgical specimens of rectal cancer in the Chinese transanal total mesorectal excision (taTME) registry collaborative (CTRC) database.Methods:The retrospective and descriptive study was conducted. Based on the concept of real-world research, the clinicopathological data of 1 761 patients with rectal cancer in the CTRC database who underwent taTME in 40 medical centers, including the Beijing Friendship Hospital of Capital Medical University et al, from November 15, 2017 to December 31, 2022 were collected. There were 1 212 males and 549 females, aged 62(range, 53-68)years. Observation indicators: (1) preoperative examinations; (2) neoadjuvant therapy; (3) postoperative examinations. Measurement data with skewed distri-bution were represented as M(range). Count data were described as absolute numbers. Results:(1) Preoperative examinations. Of the 1 761 patients, 1 324 patients underwent preoperative pelvic magnetic resonance imaging examination, and the results showed that 4 cases as clinical T0 stage, 30 cases as clinical T1 stage, 250 cases as clinical T2 stage, 828 cases as clinical T3 stage, 141 cases as clinical T4 stage, 11 cases as clinical Tx stage, 60 cases missing clinical T staging data, 490 cases as clinical N0 stage, 373 cases as clinical N1 stage, 311 cases as clinical N2 stage, 86 cases as clinical Nx stage, 64 cases missing clinical N staging data, 156 cases with mesorectal fascia invasion, 223 cases with extraintestinal blood vessels invasion. The distance from lower margin of tumor to anal margin of 1 324 patients was 50(range, 40-60)mm. (2) Neoadjuvant therapy. Of the 1 761 patients, 873 patients underwent neoadjuvant therapy, including 17 cases receiving radiotherapy alone, 155 cases receiving chemotherapy alone, 43 cases receiving short-course simultaneous chemoradiotherapy, 26 cases receiving short-course simultaneous chemoradiotherapy and delayed surgery, 1 case receiving contact radiotherapy, 277 cases receiving long-course simultaneous chemoradiotherapy, 9 cases receiving other treatments, and 345 cases missing neoadjuvant therapy data. (3) Postoperative examinations. Of the 1 761 patients, 1 584 cases achieved R 0 resection, 23 cases achieved R 1 resection, 1 case achieved R 2 resection, and there were 153 cases missing surgical margin data. The tumor diameter, number of lymph nodes harvest and positive rate of intravascular tumor thrombus were 30(range, 20-45)cm, 13(range, 10-17) and 20.794%(330/1 587) in 1 761 patients. There were 1 647 patients with circumferential margin records, which showed positive in 51 cases, and the minimum distance from deep part of tumor to circumferential margin was 5(rang, 3-13)mm in 1 647 patients. There were 547 cases with distal margin records, which showed positive in 4 cases, and the distance from lower margin of tumor to distal margin was 20(10-25)mm in 547 cases. There were 1 698 patients with specimen integrity records, which showed intact specimen in 1 436 cases, fair specimen in 233 cases, poor specimen in 8 cases, unevaluated specimen in 21 cases, and there were 20 cases with rectal tube perforation. Of the 1 761 patients, cases as pathological T0 stage, Tis stage, T1 stage, T2 stage, T3 stage, T4 stage was 103, 23, 145, 515, 712, 179, respectively, and there were 4 cases of pathology that could not be evaluated and 80 cases missing pathological T staging data. Of the 1 761 patients, cases as pathological N0 stage, N1a stage, N1b stage, N1c stage, N2a stage, N2b stage was 1 117, 189, 133, 66, 109, 68, respectively, and there were 79 cases missing pathological N staging data. Of the 1 761 patients, there were 79 cases with distant metastasis, 1 591 cases without distant metastasis, and 91 cases without data of tumor metastasis. Of the 873 patients undergoing neoadjuvant therapy, there were 405 patients with tumor regression grade records including 105 cases as grade 1, 142 cases as grade 2, 91 cases as grade 3, 43 cases as grade 4, 24 cases as grade 5. Conclusions:In China, the quality of surgical specimens of taTME for rectal cancer is good with low positive rate of resection margin. It is recommended that using a formatted postoperative pathological report for good quality control of pathological report of surgical specimen.

Clinical value of esophageal-jejunal Orvil TM anastomosis and Overlap anastomosis in laparos-copic radical total gastrectomy of adenocarcinoma of esophagogastric junction / 中华消化外科杂志

Objective:To investigate the clinical value of esophageal-jejunal OrVil TM anas-tomosis and Overlap anastomosis in laparoscopic radical total gastrectomy of adenocarcinoma of esophagogastric junction (AEG). Methods:The retrospective cohort study was conducted. The clinicopathological data of 112 patients with AEG who were admitted to the First Hospital of Jilin University from July 2017 to August 2022 were collected. There were 87 males and 25 females, aged (64±8)years. All 112 patients underwent laparoscopic total gastrectomy and D 2 lymphadenectomy, in which 61 cases with esophageal-jejunal OrVil TM anastomosis were divided into the OrVil TM group, 51 cases with esophageal-jejunal Overlap anastomosis were divided into the Overlap group. Observa-tion indicators: (1) surgical situations; (2) postoperative complications; (3) influencing factors for patients undergoing esophageal-jejunal OrVil TM anastomosis. Measurement data with normal distri-bution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the non-parameter test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Logistic regression model was used for multivariate analysis. Results:(1) Surgical situations. The esophageal invasion length and tumor diameter was 1.0(0.7,2.0)cm and (6.3±2.7)cm in patients of the OrVil TM group, versus 0.2(0.1,0.5)cm and (4.7±2.2)cm, respectively, in patients of the Overlap group, showing significant differences in the above indicators between the two groups ( Z=?6.14, t=3.26, P<0.05). (2) Postoperative complications. Cases with complications ≥Ⅲa grade of Clavien-Dindo classification, cases with respiratory system complications, cases with hydrothorax were 13, 17, 13 in the OrVil TM group, versus 4, 5, 4 in the Overlap group, showing significant differences in the above indicators between the two groups ( χ2=3.91, 5.74, 3.91, P<0.05). Cases underwent readmission within postoperative 30 days were 3 and 1 in the OrVil TM group and the Overlap group, respectively, and all patients recovered after symptomatic treatment. There were 2 cases died after operation in the OrVil TM group and none of patients died after operation in the Overlap group. (3) Influencing factors for patients undergoing esophageal-jejunal OrVil TM anastomosis. Results of multivariate analysis showed that esophageal invasion length was an independent factor influencing for patients undergoing esophageal-jejunal OrVil TM anastomosis ( odds ratio=8.25, 95% confidence interval as 3.41?19.96, P<0.05). Conclusions:Compared with esophageal-jejunal Overlap anastomosis, choosing the esophageal-jejunal Orvil TM anastomosis during laparoscopic radical total gastrectomy can take benefit to the proximal margin of patients with AEG. However, the ratios of complications ≥ Ⅲa grade of Clavien-Dindo classification, respiratory system complications and hydrothorax associated to OrVil TM anastomosis are relatively increased. Esophageal invasion length is an independent influencing factor for patients undergoing esophageal-jejunal OrVil TM anastomosis.

The safety and short-term efficacy of laparoscopic proximal gastrectomy for proximal gastric cancer and adenocarcinoma of esophagogastric junction: a multicenter study / 中华消化外科杂志

Objective:To investigate the safety and short-term efficacy of laparoscopic pro-ximal gastrectomy (LPG) for proximal gastric cancer and adenocarcinoma of esophagogastric junction.Methods:The retrospective cohort study was conducted. The clinicopathological data of 385 patients with proximal gastric cancer and adenocarcinoma of esophagogastric junction who underwent LPG in the 15 medical centers, including the First Affiliated Hospital of Xiamen University et al, from January 2014 to March 2022 were collected. There were 304 males and 81 females, aged (63±9)years. Of the 385 patients, 335 cases undergoing LPG were divided into the laparoscopic group and 50 cases undergoing open proximal gastrectomy were divided into the open group. Observation indicators: (1) intraoperative and postoperative situations; (2) follow-up; (3) stratified analysis. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Wilcoxon rank sum test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Repeated measurement data were analyzed using the repeated ANOVA. Results:(1) Intraoperative and postoperative situations. The operation time, cases with reconstruction of digestive tract as esophagogastric anastomosis and esophageal-jejunal anastomosis, cases with postoperative pathological staging as stage 0?Ⅰ and stage Ⅱ?Ⅲ, duration of postoperative hospital stay, cases with postoperative early complications were (212±96)minutes, 270, 65, 177, 107, 10(range, 8?14)days, 40 in patients of the laparoscopic group, with 51 cases missing the data of postoperative pathological staging. The above indicators were (174±90)minutes, 39, 11, 22, 28, 10(range, 8?18)days, 10 in patients of the open group. There were significant differences in the opera-tion time and postoperative pathological staging between the two groups ( t=2.62, χ2=5.93, P<0.05), and there was no significant difference in the reconstruction of digestive tract, duration of post-operative hospital stay, postoperative early complications between the two groups ( χ2=0.19, Z=0.40, χ2=2.50, P>0.05). (2) Follow-up. Of the 385 patients,202 cases were followed up during the post-operative 12 months, including 187 cases in the laparoscopic group and 15 cases in the open group. Cases with reflux esophagitis, cases with esophageal anastomotic stenosis were 48, 11 in patients of the laparoscopic group, versus 5, 2 in patients of the open group, showing no significant difference in the above indicators between the two groups ( P>0.05). The body mass index (BMI), hemoglobin (Hb), albumin (Alb) at postoperative 6 months and 12 months were (21±3)kg/m 2, (130±15)g/L, (40±4)g/L and (21±3)kg/m 2, (132±14)g/L, (41±4)g/L in patients of the laparoscopic group, versus (21±3)kg/m 2, (121±19)g/L, (37±5)g/L and (21±3)kg/m 2, (125±21)g/L, (43±6)g/L in patients of the open group. There were significant differences in postoperative Hb between the two groups ( Fgroup=5.88, Ftime=5.49, Finteraction=19.95, P<0.05) and there were significant differences in time effect of postopera-tive BMI and Alb between the two groups ( Ftime=9.53, 49.88, P<0.05). (3) Stratified analysis. ① Incidence of postoperative of reflux esophagitis and esophageal anastomotic stenosis in patients with different reconstruction of digestive tract. Of the 202 patients, cases with reconstruction of digestive tract as esophagogastric anastomosis and esophageal-jejunal anastomosis were 168 and 34, respectively. The incidence rates of postoperative of reflux esophagitis were 26.79%(45/168)and 23.53%(8/34)in cases with reconstruction of digestive tract as esophagogastric anastomosis and esophageal-jejunal anastomosis, showing no significant difference between them ( χ2=0.16, P>0.05). Cases undergoing esophageal anastomotic stenosis were 13 in patients with reconstruction of diges-tive tract as esophagogastric anastomosis. ② The BMI, Hb, Alb in patients with different reconstruc-tion of digestive tract. The BMI, Hb, Alb were (24±3)kg/m 2, (135±20)g/L, (41±5)g/L in the 168 patients with reconstruction of digestive tract as esophagogastric anastomosis before the operation, versus (23±3)kg/m 2, (130±19)g/L, (40±4)g/L in the 34 patients with reconstruction of digestive tract as esophageal-jejunal anastomosis before the operation, showing no significant difference between them ( t=1.44, 1.77, 1.33, P>0.05). The BMI, Hb, Alb at postoperative 6 months and 12 months were (21±3)kg/m 2, (128±16)g/L, (39±4)g/L and (21±3)kg/m 2, (131±16)g/L, (41±4)g/L in the 168 patients with reconstruction of digestive tract as esophagogastric anastomosis, versus (20±4)kg/m 2, (133±13)g/L, (43±3)g/L and (21±3)kg/m 2, (135±12)g/L, (44±3)g/L in the 34 patients with reconstruction of digestive tract as esophageal-jejunal anastomosis. There were significant differences in the group effect and time effect of postoperative Alb between patients with different reconstruction of diges-tive tract ( Fgroup=15.82, Ftime=5.43, P<0.05), and there was also a significant difference in the time effect of postoperative BMI between them ( Ftime=4.22 , P<0.05). Conclusion:LPG can be used to the treatment of proximal gastric cancer and adenocarcinoma of esophagogastric junction, with a good safety and short-term efficacy.

Neurologic involvement in children with coronavirus disease 2019 / 中国小儿急救医学

The clinical manifestations of neuropathies associated with novel coronavirus infection are diverse, including headache, mental disorders, acute encephalitis(meningitis), acute disseminated cerebrospinal meningitis, Guillain-Barre syndrome, acute encephalopathy and even acute (hemorrhagic) necrotic encephalopathy, which can be attributed to a variety of potential pathophysiological mechanisms.The severity of cytokine storm, vascular endothelial cell injury (including blood-brain barrier) and hypoxic ischemic injury determines the prognosis of infected patients.The treatment mainly includes general supportive therapy and immune regulation.Clinicians need to monitor and evaluate the degree of brain dysfunction and prognosis, and ensure timely treatment.

Research progress of circadian rhythm and circadian clock gene regulation in the development of myopia / 国际眼科杂志(Guoji Yanke Zazhi)

With the development of society, the incidence of myopia and the population of myopia has increased year by year, which has become a major public health problem. Therefore, the research on the pathogenesis and prevention and control measures of myopia is imminent. In recent years, the role of the biological clock in the development of myopia has gradually attracted scholars interest. Now the author starts from the impact of the biological clock on the axial length, retina and choroid in the development of myopia. In order to provide new ideas for the study of prevention and control measures and the pathogenesis of myopia, a brief review is made from the perspective of contemporary society and disrupted body clock.

Therapeutic potential of targeting SIRT1 for the treatment of Alzheimer's disease / 生理学报

Silent information regulator 1 (SIRT1) is one of the seven mammalian proteins of the sirtuin family of NAD+-dependent deacetylases. SIRT1 plays a pivotal role in neuroprotection and ongoing research has uncovered a mechanism by which SIRT1 may exert a neuroprotective effect on Alzheimer's disease (AD). Growing evidence demonstrates that SIRT1 regulates many pathological processes including amyloid-β precursor protein (APP) processing, neuroinflammation, neurodegeneration, and mitochondrial dysfunction. SIRT1 has recently received enormous attention, and pharmacological or transgenic approaches to activate the sirtuin pathway have shown promising results in the experimental models of AD. In the present review, we delineate the role of SIRT1 in AD from a disease-centered perspective and provides an up-to-date overview of the SIRT1 modulators and their potential as effective therapeutics in AD.

Empirical analysis on lumbar disc herniation treated with "sinew-bone three needling technique" of Chinese medicine / 中国针灸

The paper presents professor WU Han-qing's experience in treatment of lumbar disc herniation (LDH) with "sinew-bone three needling technique" of Chinese medicine. Based on the theory of meridian sinew, the points are located by "three-pass method" in terms of the distribution of meridian sinew and syndrome/pattern differentiation. The cord-like muscles and adhesion are relieved by relaxing technique to work directly on the affected sites and alleviate the local compression to the nerve root. The needle technique is operated flexibly according to the affected regions involved, due to which, the needling sensation is increased while the safety ensured. As a result, the meridian qi is enhanced, the mind and qi circulation is regulated; and the clinical effect is improved.

Recent progress of epigallocatechin 3-gallate for treatment of Parkinson's disease / 中国药理学通报

Epigallocatechin 3-gallate (EGCG) is an abundant polyphenolie component originating from green tea extract that has exhibited versatile bioactivities in combating several diseases. During the last decade, EGCG are effective in experimental models of Parkinson's disease (PD). Several experimental studies suggest the pleiotropic neuroprotective effects, aiding to EGCG as an appealing therapeutic strategy in PD. Therefore, in this review we focus on the effects of EGCG on anti-apoptosis, anti-oxidant, anti-inflammation, modulation of dopamine production, and the aggregation of a-synuclein. We aim to compile the recent updates and cellular and molecular mechanisms of neuroprotection of EGCG in PD. This review highlights the pharmacological features of EGCG and its therapeutic implications in PD.

Advance on small molecule self-assembled nano-drug delivery system / 药学学报

Since the application of biomedical nanotechnology in the field of drug delivery breathes new life into the research and development of high-end innovative agents, a substantial number of novel nano-drug delivery systems (nano-DDSs) have been successively developed and applied in the clinical practice. Among them, small molecule pure drug and prodrug-based nanoassemblies have grasped great attention, owing to the facile fabrication, ultrahigh drug loading and feasible industrial production. Herein, we provide an overview on the latest updates of small-molecule nanoassemblies. Firstly, the self-assembled prodrug-based nano-DDSs are introduced, including nanoassemblies formed by amphiphilic monomeric prodrugs, hydrophobic monomeric prodrugs and dimer monomeric prodrugs. Then, the recent advances on nanoassemblies of small molecule pure chemical drugs and biological drugs are presented. Furthermore, carrier-free small-molecule hybrid nanoassemblies of pure drugs and/or prodrugs are summarized and analyzed. Finally, the rational design, application prospects and clinical challenges of small-molecule self-assembled nano-DDSs are discussed and highlighted. This review aims to provide scientific reference for constructing the next generation of nanomedicines.

Role of lipopolysaccharide in the development and progression of liver cancer / 临床肝胆病杂志

Liver cancer is an important public health issue worldwide. With the improvements in high-throughput sequencing and gene editing techniques in recent years, studies have further revealed the biological mechanism of intestinal microflora in the development, progression, and metastasis of liver cancer via the gut-liver axis, and in particular, it has been found that lipopolysaccharide, a component of the outer membrane of gram-negative bacteria, can cause downstream immune cascade reactions. This article reviews the possible mechanism of action of intestinal microflora lipopolysaccharide in the development and progression of liver cancer from the aspects of the association between intestinal environmental changes and liver cancer, immunoregulation by lipopolysaccharide, and preclinical treatment.

Discovery of novel phosphodiesterase-1 inhibitors for curing vascular dementia: Suppression of neuroinflammation by blocking NF-κB transcription regulation and activating cAMP/CREB axis

Vascular dementia (VaD) is the second commonest type of dementia which lacks of efficient treatments currently. Neuroinflammation as a prominent pathological feature of VaD, is highly involved in the development of VaD. In order to verify the therapeutic potential of PDE1 inhibitors against VaD, the anti-neuroinflammation, memory and cognitive improvement were evaluated in vitro and in vivo by a potent and selective PDE1 inhibitor 4a. Also, the mechanism of 4a in ameliorating neuroinflammation and VaD was systematically explored. Furthermore, to optimize the drug-like properties of 4a, especially for metabolic stability, 15 derivatives were designed and synthesized. As a result, candidate 5f, with a potent IC50 value of 4.5 nmol/L against PDE1C, high selectivity over PDEs, and remarkable metabolic stability, efficiently ameliorated neuron degeneration, cognition and memory impairment in VaD mice model by suppressing NF-κB transcription regulation and activating cAMP/CREB axis. These results further identified PDE1 inhibition could serve as a new therapeutic strategy for treatment of VaD.

Whole-course management strategies for gastroesophageal reflux disease: an evidence mapping study based on clinical practice guidelines / 中华胃肠外科杂志

Gastroesophageal reflux disease (GERD) is one of the most common digestive diseases with high incidence, complicated clinical symptoms, difficulties in standard treatment, and heavy medical burden. At present, some GERD-relevant clinical practice guidelines (CPGs) have been issued by different countries and academic organizations, but some recommendations were inconsistent, which has caused some problems for the current clinical whole-course management of GERD. To summarize the relevant evidence among the CPGs on GERD and formulate the whole- course management strategies, we included GERD-relevant CPGs published or updated after 2010 by searching websites of guidelines, relevant professional societies, and electronic databases. We extracted the recommendations and summarized the evidence from the aspects of symptoms, epidemiology, diagnosis and treatment, which was presented in the form of evidence mapping. We included 24 CPGs, including three in Chinese and 21 in English. The clinical practice management strategies of GERD were formulated based on the evidence from the aspects of clinical symptoms, diagnostic methods, medical treatment, anti-reflux surgery and endoscopic treatment, psychological treatment, and traditional Chinese medicine treatment.

Salvianolic acid A contributes to cartilage endplate cell restoration by regulating miR-940 and miR-576-5p / 中国骨伤

OBJECTIVE@#To investigate whether Salvianolic acid A (SAA) can restore cartilage endplate cell degeneration of intervertebral discs and to identify the mechanism via regulation of micro-RNA.@*METHODS@#Cartilage endplate cells were isolated from lumbar intervertebral disc surgical samples and were treated with serum containing a series of concentrations of SAA (2, 5, and 10 ?M) for 24, 48, and 72 h to identify a proper dose and treatment time of SAA. The effect SAA on interlenkin-1β (IL-1β)-induced extracellular matrix degradation of cartilage endplate cells were analyzed by Alcian blue staining and assessment of the expression levels of ADAMTS-5, MMP3 and Col2a1. Further, the potential target miRNAs were preliminarily screened by micro-RNA sequencing combining qRT-PCR and Western blot, and then, the miRNAs mimics and inhibitors were used to verify the regulatory effect of SAA on potential target miRNAs.@*RESULTS@#The 10 μM SAA treatment for 48 h significantly enhanced the viability of cartilage endplate cells, and increased Col2a1 expression and glycosaminoglycan accumulation that were repressed by IL-1β, and reduced the effect of IL-1β on ADAMTS-5, and MMP3. Screening analysis based on micro-RNA sequencing and Venny analysis identified the downstream micro-RNAs, including miR-940 and miR-576-5p. Then, the miR-940-mimic or miR-576-5p-mimic were transfected into CEPCs. Compared with the SAA group, the expression of ADAMTS-5 and MMP3 increased significantly and the expression of COL2A1 obviously decreased after overexpression of miR-940 or miR-576-5p in CEPCs.@*CONCLUSION@#Salvianolic acid A attenuated the IL-1β-induced extracellular matrix degradation of cartilage endplate cells by targeting regulate the miR-940 and the miR-576-5p.

Isolation and identification of chemical constituents from aerial parts of Glycyrrhiza uralensis / 中国中药杂志

The present study investigated the chemical constituents from the aerial parts of Glycyrrhiza uralensis. The ethanol extract of the aerial parts of G. uralensis was separated and purified by different column chromatographies such as macroporous resin, silica gel, and Sephadex LH-20, and through preparative HPLC and recrystallization. Thirteen compounds were isolated and identified as(2S)-6-[(Z)-3-hydroxymethyl-2-butenyl]-5,7,3'-trihydroxy-4'-methoxy-dihydroflavanone(1),(2S)-8-[(E)-3-hydroxymethyl-2-butenyl]-5,7,3',5'-tetrahydroxy-dihydroflavanone(2), α,α'-dihydro-5,4'-dihydroxy-3-acetoxy-2-isopentenylstilbene(3), 6-prenylquercetin(4), 6-prenylquercetin-3-methyl ether(5), formononetin(6), 3,3'-dimethylquercetin(7), chrysoeriol(8), diosmetin(9),(10E,12Z,14E)-9,16-dioxooctadec-10,12,14-trienoic acid(10), 5,7,3',4'-tetrahydroxy-6-prenyl-dihydroflavanone(11), naringenin(12), dibutylphthalate(13). Compounds 1-3 are new compounds, and compounds 10 and 13 are isolated from aerial parts of this plant for the first time.

Recommendations on off-label antibiotics use in PICU / 中国小儿急救医学

Off-label antibiotics use in pediatric intensive care unit is not rare.Off-label antibiotics use is due to indication, age, dosage, frequency, route and method of administration, course of treatment, etc.It is necessary and reasonable for off-label antibiotics use in clinical practice, but there are also some risks.Off-label antibiotics use in clinical practice should follow the corresponding principles and standardized management.Drug treatment decisions should always be made on the basis that the individual child would be ultimately benefit.

Comparison of perioperative complications and oncological results of transanal total mesorectal excision and robot assisted total mesorectal excision / 国际外科学杂志

Objective:To explore the perioperative safety and oncological results of laparoscopic assisted transanal total mesorectal excision (TaTME) and robot assisted total mesorectal excision (TME) in radical resection of low rectal cancer.Methods:A single center retrospective study was conducted. Analyzed the clinical data of 54 patients with low rectal cancer who received robot assisted TME or laparoscopic assisted TaTME in the first hospital of Jilin University from January 2020 to July 2022, including 39 males and 15 females, with a median age of 61 years old. They were divided into robot assisted TME group ( n=29) and laparoscope assisted TaTME group ( n=25) according to the surgical methods. Follow-up was carried out through outpatient, telephone and wechat. The follow-up time was 30 days after operation. The quality of mesorectal excision was divided into high quality and low quality according to the evaluation of the integrity of the mesentery of the specimen after total mesorectal excision and the circumferential cutting edge. The primary outcome was the quality of mesorectal excision, and the secondary end points were surgery related information, postoperative pathological information, and postoperative complications. SPSS25.0 software was used for statistical analysis. The measurement data of skew distribution were expressed by M( Q1, Q3), and the Mann Whitney U test was used for comparison between groups. The counting data were expressed by n(%), and the comparison between groups was conducted by χ2 test or Fisher exact probability method. Results:The high-quality mesorectal excision rate in TaTME group was 88% (22 cases), and the high-quality mesorectal excision rate in robot group was 100%, with no statistical difference( χ2=3.69, P=0.093). The operation time of TaTME group and robot assisted TME group was [180 (165, 220)] min and [140 (117, 168)] min, respectively, with statistical significance ( U=125.00, P<0.001). The preventive ileostomy rate was 100% in the TaTME group and 37.9% in the robot group( χ2=23.27, P<0.001). Compared with TaTME group, robot assisted TME had a longer distance from the lower tumor to the distal cutting edge [10 (5, 25) mm vs 35 (21, 41) mm, U=117.00, P<0.001], a longer distance from the deepest tumor to the circumferential cutting edge [15 (10, 25) mm vs 25 (20, 34) mm, U=165.50, P=0.003], and a larger tumor maximum meridian [20 (4, 52) mm vs 42 (30, 48) mm, U=202.50, P=0.005]. The total incidence of complications within 30 days after operation was 16.7%, of which the incidence of Clavien-Dindo Ⅰ to Ⅱ complications was 11.1%, and the incidence of Clavien-Dindo ⅢA complications was 5.6%. The overall complication rate of TaTME group was higher, but there was no significant difference (20.0% vs 13.8%, χ2=0.37, P=0.718). Conclusion:Both TaTME and robot assisted TME can ensure good quality of TME operation and can be used as an effective and safe treatment for low rectal cancer. When performing TaTME surgery for low rectal cancer, it is more necessary to ensure sufficient distal margin distance.

Recent progress of neuroprotective mechanisms of luteolin in Alzheimer's disease / 中国药理学通报

Luteolin is a widely distributed type of flavone herbsand vegetables, which has diverse pharmacological activities against human ailments including Alzheimer's disease(AD). Recently, luteolin has been the most widely studied phytochemicals for their neuroprotective effects against experimental models of AD. Luteolin also improves brain insulin sensitivity and neuroinflammation, which attenuates the phosphorylation of tau and the formation of tangles, and the tendency of Aβ to form deposits. Furthermore, luteolin has anti-oxidative stress and anti-apoptosis effect in AD. The present study aims at reviewing experimental studies and describing the possible underlying molecular mechanisms by which luteolin and the related compounds protect against AD.