Parkinson's disease (PD) is a chronic neurodegenerative disease. At present, levodopa and other drugs are mainly used for dopamine supplementation therapy. However, the absorption of levodopa in the gastrointestinal tract is unstable and its half-life is short, and long-term use of levodopa will lead to the end-of-dose deterioration, dyskinesia, the "ON-OFF" phenomenon and other symptoms. Therefore, new preparations need to be developed to improve drug efficacy, reduce side effects or improve compliance of patients. Based on the above clinical needs, this review briefly introduced the preparation modification strategies for the treatment of PD through case analysis, in order to provide references for the research and development of related preparations.

Objective To investigate the effects of inhibiting KDM2A gene on the proliferation,invasion and migration of liver cancer cells and its possible regulatory mechanism.Methods Forty pairs of HCC tissues and their adjacent normal counterparts were collected from 2014 to 2017 in Tongji Hospital,Tongji Medical College Affiliated to Huazhong University of Science and Technology.Human liver cancer cell lines HepG2,Huh7,HCCLM3,MHCC-97H and normal liver cells LO2 were cultured in vitro.The mRNA and protein expression levels of KDM2A in HCC tissues and cells were detected by qRT-PCR and Western blotting.Huh7 cells were taken and set up as follows:(1)si-NC group(transfected with si-NC)and si-KDM2A group(transfected with si-KDM2A);(2)mimic-NC group(transfected with mimic-NC),miRNA-29a-3p mimic group(transfected with miRNA-29a-3p mimic),inhibitor-NC group(transfected with inhibitor-NC)and miRNA-29a-3p inhibitor group(transfected with miRNA-29a-3p inhibitor).The mRNA and protein expression levels of KDM2A were detected by qRT-PCR and Western blotting.The invasion and migration of cells were detected by Transwell,the proliferation of cells was detected by CCK-8 methods.The online databases TargetScan,miRDIP,miRWalk,Starbase and miRDB were used to predict the binding sites of KDM2A and miR-29a-3p.The KDM2A 3'-UTR(WT)or KDM2A 3'-UTR(MUT)report plasmid was co-transfected with NC-miRNA or miR-29a-3p mimics respectively for 48 h in 293T cells,and the luciferase activity was detected by the luciferase reporter gene detection system.Results Compared with adjacent normal counterparts,the relative mRNA and protein expression levels of KDM2A in HCC tissues increased significantly(P＜0.05).Compared with LO2,the relative mRNA and protein expression levels of KDM2A in HepG2,Huh7,HCCLM3 and MHCC-97H increased significantly(P＜0.05).Compared with si-NC group,the proliferation,invasion and migration of Huh7 cells in si-KDM2A group decreased significantly(P＜0.05 or P＜0.01).The analysis results of TargetScan,miRDIP,miRWalk,Starbase and miRDB showed that there were binding sites between KDM2A and miR-29a-3p.The results of the dual luciferase reporter assay showed that miR-29a-3p mimic significantly reduced KDM2A-MUT luciferase activity(P＜0.01).After overexpression of miRNA-29a-3p,the relative mRNA and protein expression levels of KDM2A were decreased(P＜0.01),the proliferation,invasion and migration abilities were decreased(P＜0.05)in Huh7 cells.After inhibiting the expression of miRNA-29a-3p,the relative mRNA and protein expression levels of KDM2A were increased(P＜0.05),the proliferation,invasion and migration abilities were enhanced(P＜0.05)in Huh7 cells.Conclusion Inhibiting the expression of KDM2A can reduce the proliferation and migration ability of Huh7 cells.miR-29a-3p may be the upstream regulator of KDM2A and participate in the occurrence and development of hepatocellular carcinoma.

Limosilactobacillus reuteri is a microbe intricately linked to humans and animal health.A thor-ough assessment of its safety and potential benefits is imperative prior to its application in human and ani-mals.In this investigation,we performed a comprehensive analysis encompassing genome sequencing,genomic analysis,and phenotypic characterization of L.reuteri Q35,an exceptionally proficient producer of reuterin.The whole genome sequencing results showed that the complete genome sequence spans 2145158 bp with a GC content of 38.9％ and encompasses 2121 genes.Initial identification of antibiotic-re-sistant genes,virulence factors,and toxin-coding genes in the genome substantiated the strain' s low-risk status.Subsequent tests for antibiotic resistance,acute oral toxicology,and hemolysis further confirmed its elevated safety level.The genome of L.reuteri Q35 was found to contain genes associated with adhe-sion and stress tolerance.Following exposure to artificial gastric juice and bile salt,the strain exhibited a higher survival rate and demonstrated a strong scavenging ability for hydroxyl free radicals in antioxidant capacity tests.These findings suggested that L.reuteri Q35 possesses unique probiotic properties.Addi-tionally,the genome of strain Q35 harbors three truncated oxaloyl-CoA decarboxylase genes (oxc1,oxc2 and oxc3),overexpression of which resulted in a significant increase in ammonium oxalate degradation from 29.5％ to 48.8％.These findings highlight that L.reuteri Q35 exhibits both favorable safety charac-teristics alongside beneficial properties,making it a promising candidate for treating metabolic disorders such as hyperoxaluria.

The taste of drugs has an important impact on the compliance of patients, but most of the active drug ingredients have an uncomfortable taste, especially traditional Chinese medicine. Through a variety of pharmaceutical excipients with taste masking properties combined with corresponding technologies can improve the taste of drugs and the characteristics of other dosage forms, so as to improve patient compliance. Here, we mainly summarize the auxiliary materials used for taste masking, explain the mechanism of taste masking from the point of view of excipients and introduces related uses, so as to provide reference for further research on taste masking of pediatric preparations.

Good medicine tastes bitter, but it is often difficult to swallow because the drug is bitter and astringent, so that the compliance of patients with medication is poor. However, the use of taste masking technology can better improve this situation. Appropriate and effective taste masking technology can improve the drug compliance of patients, especially children, it can also improve the curative effect and the clinical value of drugs. Herein, we summarize the latest research progress of taste masking technology, and summarize the traditional taste masking technology from the aspects of action mechanisms and application scopes. Finally, the novel and efficient taste masking technologies were presented.

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

Objective:To evaluate the clinical outcome of Robot-assisted sacroiliac screw fixation in the treatment of fragility fracture of the sacrum in the elderly.Methods:From March 2016 to June 2022, a retrospective analysis was performed on 30 patients with fragility fractures of the sacrum in the elderly who accepted robot-assisted sacroiliac screw to treat fragility fractures of the sacrum in our hospital. There were 12 males and 18 females with average age 71.03±8.25 years (range, 60-89 years). According to the classification of fragility fractures of the pelvis (FFP) in the elderly, there were 22 patients with FFP II, 2 patients with FFP III, and 6 patients with FFP IV. Surgical planning was based on the average CT value of S 1 channel and whether there is a transsacral screw channel. Robot-assisted sacroiliac screw fixation was performed during surgery. The pain of pre-operation and post-operation was evaluated using the visual analogue scale (VAS), the position of sacroiliac screws was evaluated by Gras grading, and the degree of functional recovery after surgery was evaluated using the Majeed function score. Results:All 30 patients successfully completed the operation. The mean operation time was 27.00±6.68 min (range, 18-35 min), the mean fluoroscopy times were 27.13±5.16 (range, 18-34), and the mean blood loss was 30.53±6.61 ml (range, 23-38 ml). All patients were followed up, and the mean follow-up time was 19.03±7.8 months (range, 8-25 months). The VAS was 5(5, 6), 4(3, 4), 3(2, 3), 0(0, 1) points before surgery, 1 week, 2 months and 6 months after surgery, respectively, and the difference was statistically significant ( H=103.26, P<0.001). After the surgery of 2 months, 6 months and the last follow-up time, the Majeed function scores were 88(83, 90), 91(87, 92), 92(90, 93) points, respectively, and the difference was statistically significant ( H=19.59, P<0.001). Screw position was evaluated according to Gras grading at 3 days after surgery, including 28 cases of level I, 2 cases of level II, and no screw penetrated the cortical bone or entered the sacral canal or sacral foramen. No vascular or nerve injury occured during the operation. 28 patients with FFS met the fracture healing criteria, and the healing time was 4.54±1.57 months (range, 3-7 months). Two patients had bone nonunion, one of whom underwent anterior ring plate removal due to infection of the pelvic anterior wound, and one month later, pelvic CT scan revealed loosening of the sacroiliac screw; the other one is considered to be related to too early weight bearing. Conclusion:For fragility fractures of the sacrum in elderly, Robot-assisted sacroiliac screw is an effective minimally invasive treatment, with high accuracy of screw placement, effective pain reduction, improved fracture healing rate, and achieve the satisfactory clinical efficacy.

Objective: To investigate the application effect of augmented reality and mixed reality navigation technology in three-dimensional(3D) laparoscopic narrow right hepatectomy(LRH). Methods: A retrospective analysis was performed on the clinical data of 5 patients with hepatic malignancy admitted to the First Department of Hepatobiliary Surgery,Zhujiang Hospital,Southern Medical University from September 2020 to June 2021,all of whom were males,aged from 42 to 74 years.Preoperative evaluation was performed using the self-developed 3D abdominal medical image visualization system; if all the 5 patients were to receive right hemihepatectomy,the remnant liver volume would be insufficient,so LRH were planned.During the operation,the independently developed 3D laparoscopic augmented reality and mixed reality surgical navigation system was used to perform real-time multi-modal image fusion and interaction between the preoperative 3D model and 3D laparoscopic scene.Meanwhile,intraoperative ultrasound assisted indocyanine green fluorescence was used to determine the surgical path.In this way,the LRH under the guidance of augmented reality and mixed reality navigation was completed.The predicted liver resection volume was evaluated before surgery,actual resected liver volume,surgical indicators and postoperative complications were analyzed. Results: All the 5 patients completed LRH under the guidance of augmented reality and mixed reality navigation technology,with no conversion to laparotomy.The median operative time was 300 minutes(range:270 to 360 minutes),no intraoperative blood transfusion was performed,and the median postoperative hospital stay was 8 days(range:7 to 9 days).There were no perioperative deaths,or postoperative complications such as liver failure,bleeding,or biliary fistula. Conclusion: For patients who need to undergo LRH,the use of augmented and mixed reality navigation technology can safely and effectively guide the implementation of surgery,retain more functional liver volume,improve surgical safety,and reduce postoperative complications.
Adult ; Aged ; Augmented Reality ; Hepatectomy/methods* ; Humans ; Imaging, Three-Dimensional ; Laparoscopy/methods* ; Liver Neoplasms/surgery* ; Male ; Middle Aged ; Retrospective Studies ; Technology

Three tricyclic [6,5,7] and six tetracyclic [6,5,5,5] novel indole alkaloids were synthesized and evaluated on triglyceride inhibitory activities for the first time. Among them, compound 4c showed the most potent activity with IC₅₀ value of 6.35 μmol·L^-1. Meanwhile, compound 4c also exhibited a good safety profile at the cellular level. Preliminary mechanism study indicated that 4c might increase intracellular lipid metabolism by activating AMPK. These results provide a novel family of lead compounds for the discovery of anti-NAFLD candidates.

Aim To investigate the reeovery of I FN-7- tion and the protective effect of Prepared Radix Reh- secreting T and NK cells after low dose X-ray irradia- manniae ( PRR ).Methods X-ray 2.5Gy was used to establish a mouse irradiated model,and some irradiated mice were used to establish a melanoma lung cancer metastasis model or to be treated by PRR.The propor¬tion and number of Tel , Thl and NK1 cells with the phenotypes of IL-12R and IL-15R were detected by flow cytometry.The transcription levels of IL-12,1L- 15 ,STAT4 and T-bet were detected by RT-qPCR.Re¬sults Within four days after irradiation,Thl ,Tcl and NK1 cells were significantly reduced ( P < 0.05 , P < 0.01).The expression of IL-12R and IL-15R de¬creased in Thl and Tel cells , and increased in NK1 cells ( P < 0.05 ).On day 8 of irradiation , NK1 and Tc 1 cells recovered or exceeded basic level, but Th 1 was still lower than normal level ( P < 0.05 ) , and tumor load of irradiated mice increased significantly (P <0.01).Compared with radiation group, the propor¬tion and absolute numbers of NK1 ,Tel and Thl were up-regulated by PRR (P <0.05 <0.01) ,and tumor load was down-regulated ( P < 0.05 ).Conclusions The impaired reconstitution of Thl cells after irradia¬tion affects the anti-tumor ability.PRR promotes the recover}' of IFN-∗y-secreting T and NK cells after radia¬tion and reduces the risk of tumor metastasis in mice.