Messenger ribonucleic acid (mRNA) is a promising therapeutic drug with great potential in the fields of immunology, oncology, vaccines and inborn metabolic diseases. However, due to its instability and susceptibility to nuclease degradation, efficient delivery vectors are required. Lipid nanoparticles (LNPs) are recognized as the most mature delivery vectors due to their advantages of easy formulation, high stability, efficient cell uptake and endosomal escape. However, the accumulation of LNPs in the liver severely limits the targeting and treatment of mRNA-LNP technology beyond the liver. To overcome this obstacle, researchers have been focusing on various means to achieve precise delivery of extrahepatic tissues and organs. This article mainly expounds the research progress of LNP-specific delivery mRNA from three aspects: endogenous targeting, active targeting and selection of administration route, in order to provide ideas and directions for the design of new mRNA-LNP delivery systems in the future.

ObjectiveTo compare the effect of toe-spread-out exercises (TSO) and modified TSO in females with hallux valgus. MethodsFrom September to December, 2023, a total of 45 females with hallux valgus were recruited in Capital University of Physical Education and Sports and randomly divided into blank control group (n = 15), TSO group (n = 15), and modified TSO group (n = 15). The blank control group received no intervention, the TSO group received routine TSO, and the modified TSO group received fibularis longus fascia release followed by TSO, for eight weeks. Changes in the hallux valgus angle (HVA) and the cross-sectional area (CSA) of the abductor hallucis muscle were measured before intervention, and four and eight weeks after intervention, respectively. ResultsOne case dropped out from the blank control group. The changes of HVA in the TSO and modified TSO groups were significantly greater than in the blank control group (F > 15.263, P < 0.05). After four weeks of intervention, the change of left HVA in the modified TSO group was significantly greater than in the TSO group (P < 0.05). The main effect of time was significant on the CSA of the abductor hallucis muscle (F > 13.245, P < 0.05). The main effect of group was significant on the left foot's CSA of the abductor hallucis (F = 3.798, P < 0.05). The interaction effect of time and group was also significant (F > 4.744, P < 0.05). The CSA of the abductor hallucis in both the TSO and modified TSO groups after four weeks and eight weeks of intervention was significantly greater than before intervention (P < 0.05). At eight weeks, the CSA of the right foot in the modified TSO group was significantly greater than in the blank control group (P < 0.05). ConclusionBoth TSO and modified TSO can improve HVA and the CSA of the abductor hallucis muscle in females with hallux valgus, and modified TSO is better.

Background Obsessive-compulsive personality disorder and obsessive-compulsive disorder(OCD)are common psychological disorders with similar clinical symptoms,but the differences between the two need further clarification.Objective To explore the clinical features of and influencing factors of obsessive-compulsive personality disorder in patients with OCD,so as to provide references for further relevant clinical diagnosis and treatment.Methods A total of 195 patients with OCD were selected as the research subjects,who received treatment at the outpatient and inpatient departments of the Affiliated Brain Hospital of Nanjing Medical University from July 2022 to December 2023 and met the diagnostic criteria for OCD in the International Classification of Diseases,tenth edition(ICD-10).Evaluation was conducted by using the Yale-Brown Obsessive Compulsive Scale(Y-BOCS),Personality Diagnostic Questionnaire-4+(PDQ-4+),Obsessive-Compulsive Inventory-Revised(OCI-R),Beck Depression Inventory(BDI),Beck Anxiety Inventory(BAI)and Sheehan Disability Scale(SDS).In accordance with the score of Obsessive-Compulsive Personality Disorder Scale in PDQ-4+,patients were divided into the OCD group with obsessive-compulsive personality disorder(n=58)and the OCD group without obsessive-compulsive personality disorder(n=137).Pearson correlation analysis and Spearman correlation analysis were adopted to examine the correlation between clinical features and the score of the Obsessive-Compulsive Personality Disorder Scale.Multiple linear regression analysis was used to explore the influencing factors of OCD patients with obsessive-compulsive personality disorder.Results Statistically significant differences were observed between OCD patients with and without obsessive-compulsive personality disorder in the age,family history of mental illness,time without treatment,hoarding and ranking dimension scores in OCI-R,OCI-R total score,score of Obsessive-Compulsive Personality Disorder Scale in PDQ-4,and BDI score(P≤0.05).OCD patients with obsessive-compulsive personality disorder in the time without treatment,OCI-R total score,hoarding and ranking dimension scores in OCI-R and BDI score are all positively correlated with the score of the Obsessive-Compulsive Personality Disorder Scale(r=0.120,0.526,0.364,0.492,0.414,P<0.05).The results of multiple linear regression analysis showed that time without treatment(β=0.132,P<0.05),hoarding dimension score(β=0.283,P<0.05)and ranking dimension score in OCI-R(β=0.418,P<0.05)were the influencing factors of OCD patients with obsessive-compulsive personality disorder.Conclusion OCD patients with obsessive-compulsive personality disorder may have longer untreated periods,more pronounced functional impairments in hoarding and sorting and more severe depressive symptoms.Untreated time,hoarding symptoms and sorting symptoms may be influencing factors for OCD patients with obsessive-compulsive personality disorder.

Objective To explore the current research status,collaboration situation,hot spots and development trend of thermal ablation therapy for the treatment of hepatocellular carcinoma(HCC).Methods The Web of Science core collection database was searched,and the visualization analysis of the recent core literature was accomplished by using CiteSpace software.Results A total of 1385 core collections were enrolled in this study,and China was the country with the largest number of published academic papers.The most cited references was the theses published by Bruix,et al.The key words included radiofrequency ablation,microwave ablation,percutaneous ethanol injection,immunotherapy,fusion imaging,etc.,which could be divided into 6 clusters and 15 emergent words.Conclusion Thermal ablation of HCC has been a research hot spot in HCC treatment.This technology has been gradually maturing,and it,being combined with imaging technology and other therapeutic methods,has achieved continuous development and plays an important role in the clinical treatment of HCC.

Objective To discuss the development trend of radiofrequency ablation for benign thyroid nodules.Methods The Web of Science core ensemble database was searched for the published literature concerning the radiofrequency ablation for benign thyroid nodules,and CiteSpace software was used to complete the visualization analysis of the core literature published in recent years.Results A total of 396 core ensembles were included in this analysis,and during the period from 2013 to 2022 the number of published papers had maintained an increasing trend.China was the country that had the largest number of published papers.Baek and Jung Hwan were the authors who had the largest number of published papers,and Ulsan University had the largest number of published papers.The theses published by Kim et al were the most cited.Among the key words,the safety,effectiveness and long-term follow-up of radiofrequency ablation were more important.Conclusion Studies on radiofrequency ablation of benign thyroid nodules are increasing year by year,this therapy becomes gradually maturing,and more ablation methods are constantly emerging.

ObjectiveTo compare the effect of three kinds of intrinsic foot muscle exercise on flatfoot. MethodsFrom September to November, 2022, 45 subjects with flatfoot from Capital University of Physical Education and Sports were randomly divided into short foot exercise (SFE) group (n = 15), toe-spread-out exercise (TSOE) group (n = 15) and short foot & toe-spread-out exercise (SF+TSOE) group (n = 15), who received SFE, TSOE and SF+TSOE, respectively, for eight weeks. The cross-sectional area of abductor hallucis muscle, navicular drop test (NDT) and Chippaux-Smirak index (CSI) were measured before treatment, four weeks after treatment and eight weeks after treatment. ResultsThree subjects dropped out in each group. The main effect of time was significant for left and right cross-sectional area of abductor hallucis muscle, NDT and CSI (F > 13.906, P < 0.001). The main effect of group was not significant for left and right cross-sectional area of abductor hallucis muscle, NDT and CSI (F < 1.934, P > 0.05). The interaction effect of group and time was significant for left and right NDT (F > 3.044，P < 0.05), and it was better in SF+TSOE group than in SFE group and TSOE group (P < 0.05). ConclusionSF and TSOE can improve the cross-sectional area of abductor hallucis muscle and foot morphology in subjects with flatfoot, and the combination of them may be more effective.

Bariatric surgery is the most effective treatment for patients with severe obesity, which can significantly improve the metabolic disorders, especially type 2 diabetes mellitus. Bariatric and metabolic surgery is the latest and fastest-growing branch of surgery, with the types of procedure and other novel treatment modalities are still evolving and in progress. The authors summarize the recent advancement related to novel bariatric and metabolic surgery in the treat-ment of morbid obesity and type 2 diabetes mellitus in recent years through literature search, which can be divided into the following three parts: (1) novel surgical procedures and new guideline of indication. Sleeve gastrectomy and Roux-en-Y gastric bypass are the most performed bariatric surgery. Duodenal switch or the variant of one anastomosis duodenal ileostomy are also accredited procedures but been less performed. One anastomosis gastric bypass is the most recently accredited bariatric surgical procedures with better safety profile and weight loss efficacy than most of the procedures. For other novel procedures, bipartition procedure may be the next accredited proce-dure. A new worldwide guideline is recently launched and the indication for bariatric surgery is lowered BMI 27.5 kg/m 2 for Asian. (2) The effect and mechanism of bariatric surgery. Bariatric surgery can significantly reduce the incidence of cardiovascular disease and mortality in obese patients. The main beneficiary group is patients with diabetes mellitus. Along with the recent basic research and the success of new gut hormone related drugs, the mechanism of bariatric surgery can be mostly attributed to gut hormonal effect, however, gastric volume still play an important role. (3) Novel obesity treatment modalities. Endoscopic obesity treatment has a major progress in the success of endoscopic gastroplasty by endoscopic suturing designs. More noteworthy is the development of new intestinal hormone drug therapy, which can achieve a weight loss of 14% in one year by injec-ting once a week glucagon-like peptide-1 preparation, and then combining two or three intestinal hormone drugs can achieve a weight loss of 24% in one year, which is close to the effectiveness of bariatric surgery. Pharmacologic treatment of obesity is very promising and expected. With the increasing severity of obesity and diabetes mellitus in the world, in addition to the explosive develo-pment of bariatric and metabolic surgery in recent years, many new surgical methods and new treatments, especially new and effective intestinal hormone related therapeutic drugs, have been developed. The success of bariatric and metabolic surgery depends on a multidisciplinary team with rich clinical experience: precise preoperative planning and comprehensive postoperative manage-ment, as well as patient understanding and cooperation, in order to achieve the best results.

BACKGROUND: Management of gastric leak after sleeve gastrectomy (SG) is challenging due to its unpredictable outcomes. We aimed to summarize the characteristics of SG leaks and analyze interventions and corresponding outcomes in a real-world setting. METHODS: To retrospectively review of 15,721 SG procedures from 2010 to 2020 based on a national registry. A cumulative sum analysis was used to identify a fitting curve of gastric leak rate. The Kaplan-Meier method and log-rank tests were performed to calculate and compare the probabilities of relevant outcomes. The logistic regression analysis was conducted to determine the predictors of acute leaks. RESULTS: A total of 78 cases of SG leaks were collected with an incidence of 0.5% (78/15,721) from this registry (6 patients who had the primary SG in non-participating centers). After accumulating 260 cases in a bariatric surgery center, the leak rate decreased to a stably low value of under 1.17%. The significant differences presented in sex, waist circumference, and the proportion of hypoproteinemia and type 2 diabetes at baseline between patients with SG leak and the whole registry population ( P = 0.005, = 0.026, <0.001, and = 0.001, respectively). Moreover, 83.1% (59/71) of the leakage was near the esophagogastric junction region. Leakage healed in 64 (88.9%, 64/72) patients. The median healing time of acute and non-acute leaks was 5.93 months and 8.12 months, respectively. Acute leak (38/72, 52.8%) was the predominant type with a cumulative reoperation rate >50%, whereas the cumulative healing probability in the patients who required surgical treatment was significantly lower than those requring non-surgical treatment ( P = 0.013). Precise dissection in the His angle area was independently associated with a lower acute leak rate, whereas preservation ≥2 cm distance from the His angle area was an independent risk factor. CONCLUSIONS Male sex, elevated waist circumference, hypoproteinaemia, and type 2 diabetes are risk factors of gastric leaks after SG. Optimizing surgical techniques, including precise dissection of His angle area and preservation of smaller gastric fundus, should be suggested to prevent acute leaks.
Humans ; Male ; Retrospective Studies ; Diabetes Mellitus, Type 2/complications* ; Obesity, Morbid ; Anastomotic Leak/epidemiology* ; Gastrectomy/methods* ; Reoperation/methods* ; Registries ; Laparoscopy/methods* ; Treatment Outcome

ObjectiveTo systematically review the effects of short-foot exercise on adult flatfoot. MethodsArticles related to short-foot exercise for flatfoot were searched from PubMed, Web of Science, Cochrane, Embase, Scopus, CNKI, Wanfang Data and CBM, from January, 2010 to December, 2022. The methodological quality was evaluated with the Physiotherapy Evidence Database (PEDro) scale, and the relevant data were extracted. ResultsTen randomized controlled trials were included, involved 335 individuals. The mean score of the PEDro scale was 7.1. Short-foot exercise improved the navicular drop, posture index score, balance and cross-sectional area of abductor hallucis muscle for patients with flatfoot, but plantar pressure. ConclusionShort-foot exercise can improve the foot structure, balance and adductor hallucis muscle in adult flatfoot, but plantar pressure.

OBJECTIVE To research the effect and mechanism of fermentation of Astragalus membranaceus on endogenous metabolites in hyperuricemia model rats using serum UHPLC-HRMS. METHODS The SD rats were randomly divided into different groups, including blank group, model group, benzbromarone group(20 mg·kg-1), as well as fermentation of Astragalus membranaceus high-dose(3 g·kg-1) and low-dose group(1.5 g·kg-1). Model group and each treatment group were disposed with 300 mg·kg-1 oxonic acid potassium to establish hyperuricemia models. At the time of 1 h after modeling, rats in each treatment group were given corresponding drugs for intervention. Collected rat serum after 14 d. The serum of different groups were collected for endogenous metabolites research using UHPLC-HRMS. After multivariate statistical analysis, the different metabolites and metabolic pathways were selected. RESULTS The hyperuricemia rat modes were successfully established by oxonic acid potassium 14 d, and fermentation of Astragalus membranaceus showed good uric acid reducing effect. Compared with the blank group, 17 potential biomarkers associated with hyperuricemia were found in the model group. Among them, 9 potential biomarkers were significantly recalled by fermentation of Astragalus membranaceus. It mainly involved sphingolipid metabolism, pyrimidine metabolism, tryptophan metabolism, pantothenic acid and CoA biosynthesis, glycine, serine and threonine metabolism and other pathway. CONCLUSION This study can provide a basis for revealing the mechanism of reducing uric acid by fermentation of Astragalus membranaceus, and lay a foundation for the further development and utilization of Astragalus.