Hydrogen peroxide (H₂O₂) and nitric oxide (NO) has a short half-life, low bioavailability, poor tumor targeting and systemic adverse reactions in the physiological environment. In this study, phacoemulsification and nano-precipitation were used to synthesize didecyl dimethyl ammonium bromide (DDAB)/polylactic acid nanoparticles (PLA), then L-arginine (L-Arg) and glucose oxidase (GOx)-loaded nanoparticles (GADP) were prepared, and the in vitro antitumor activity was investigated．The particle size, potential, embedding rate and the ability to produce H₂O₂/NO of the nanoparticles were investigated. Meanwhile, in vitro cell cytotoxicity against human hepatoma cells (HepG2) was evaluated．The results showed that the prepared L-Arg-DDAB/PLA (ADP) nanoparticles were spherical particles. And the particle size and zeta potential were (225.7 ± 6.33) nm and (+23.5 ± 0.12) mV, respectively. The adsorption rate of GOx was 87.23% ± 0.02%. The drug loading of L-Arg was 15.6% ± 0.22%. The pH value of glucose solution and the amount of H₂O₂ showed that GADP had good catalytic activity. In vitro cytotoxicity experiments showed that blank nanoparticles were nontoxic, while the drug-loaded nanoparticles presented enhanced antitumor effect on HepG2 cells. And can inhibit tumor cell migration. The low dose nano-scale NO delivery system GADP can effectively inhibit the migration of tumor cells and kill tumor cells, thus producing therapeutic benefits.

OBJECTIVE: To explore the mechanism of electroacupuncture (EA) in promoting recovery of the facial function with the involvement of autophagy, glial cell line-derived neurotrophic factor (GDNF), and phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling pathway. METHODS: Seventy-two male Sprague-Dawley rats were randomly allocated into the control, sham-operated, facial nerve injury (FNI), EA, EA+3-methyladenine (3-MA), and EA+GDNF antagonist groups using a random number table, with 12 rats in each group. An FNI rat model was established with facial nerve crushing method. EA intervention was conducted at Dicang (ST 4), Jiache (ST 6), Yifeng (SJ 17), and Hegu (LI 4) acupoints for 2 weeks. The Simone's 10-Point Scale was utilized to monitor the recovery of facial function. The histopathological evaluation of facial nerves was performed using hematoxylin-eosin (HE) staining. The levels of Beclin-1, light chain 3 (LC3), and P62 were detected by immunohistochemistry (IHC), immunofluorescence, and reverse transcription-polymerase chain reaction, respectively. Additionally, IHC was also used to detect the levels of GDNF, Rai, PI3K, and mTOR. RESULTS: The facial functional scores were significantly increased in the EA group than the FNI group (P<0.05 or P<0.01). HE staining showed nerve axons and myelin sheaths, which were destroyed immediately after the injury, were recovered with EA treatment. The expressions of Beclin-1 and LC3 were significantly elevated and the expression of P62 was markedly reduced in FNI rats (P<0.01); however, EA treatment reversed these abnormal changes (P<0.01). Meanwhile, EA stimulation significantly increased the levels of GDNF, Rai, PI3K, and mTOR (P<0.01). After exogenous administration with autophagy inhibitor 3-MA or GDNF antagonist, the repair effect of EA on facial function was attenuated (P<0.05 or P<0.01). CONCLUSIONS EA could promote the recovery of facial function and repair the facial nerve damages in a rat model of FNI. EA may exert this neuroreparative effect through mediating the release of GDNF, activating the PI3K/mTOR signaling pathway, and further regulating the autophagy of facial nerves.
Rats ; Male ; Animals ; Rats, Sprague-Dawley ; Electroacupuncture ; Phosphatidylinositol 3-Kinase/metabolism* ; Facial Nerve Injuries/therapy* ; Phosphatidylinositol 3-Kinases/metabolism* ; Beclin-1 ; Glial Cell Line-Derived Neurotrophic Factor ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism* ; Autophagy ; Mammals/metabolism*

Osteoporosis （OP） is a skeletal metabolic disease characterized by bone loss and destruction of bone microstructure. Changes in estrogen levels are not the only pathogenic factors for the occurrence and development of OP. MicroRNA （miRNA） plays an important regulatory role in cells. The complementary sequences of miRNA and targeted mRNA combine to inhibit the expression of targeted mRNA through post-transcriptional regulation， forming a complex regulatory network. Research suggests that miRNA is closely related to the occurrence and development of various diseases， including inflammatory diseases， metabolic diseases， and cancer. Targeted mRNA participates in post-transcriptional gene expression regulation in OP， mainly regulating the balance among bone construction， bone resorption， and osteoblast differentiation. Therefore， miRNA-based gene therapy is a rapidly developing disease treatment strategy. Traditional Chinese medicine can improve bone metabolism by intervening in miRNA differential expression to target and regulate osteogenic/osteoclast differentiation. This article summarized the targeting effects of miRNAs in physiological and developmental processes such as bone cell proliferation， differentiation， survival， and apoptosis， reviewed and classified their mechanisms of action and targets， and sorted out the current treatment methods of traditional Chinese medicine for preventing and treating OP and drugs that exert bone protective functions through miRNAs. This review is expected to provide theoretical reference and research guidance for future research on OP treatment by regulating miRNA.

Objective To investigate the effect of vitamin B6(VB6)on vascular endothelial injury of atherosclerosis(AS)mice and its mechanism.Methods Thirty-six ApoE-/-mice were randomly divided into control group,AS group,VB6 group,AS+LiCl group,AS+VB6 group and AS+VB6+LiCl group,with 6 mice in each group.The mice in the AS group,AS+LiCl group,AS+VB6 group and AS+VB6+LiCl group were fed with high-fat diet for 12 weeks to establish the AS model;the mice in the control group and VB6 group were given regular diet and normal drinking water for 12 weeks.After 12 weeks,the mice in the control group were given conventional diet and the same volume of physiological saline as the VB6 group daily by gavage;the mice in the VB6 group were given routine diet and VB6(50 mg·kg-1)by gavage daily;the mice in the AS+LiCl group were given high-fat diet continuously and LiCl(1 mg·kg-1)by gavage daily;the mice in the AS+VB6 group were given high-fat diet continuously and VB6(50 mg·kg-1)by gavage daily;the mice in the AS+VB6+LiCl group were given high-fat diet continuously and VB6(50 mg·kg-1),LiCl(1 mg·kg-1)by gavage daily;all mice were intervened for 4 weeks.After intervention,the serum nitric oxide(NO),malondialdehyde(MD A)levels and superoxide dismutase(SOD)activity of mice in each group were measured by enzyme linked immunosorbent assay.Hematoxylin-eosin staining was used to observe the morphology of thoracic aortic tissue of mice in each group and the percentage of AS plaque area to total vascular area was calculated.The vasodilatation rate of thoracic aorta was detected by isolated vascular ring experiment.The expression of sodium/hydrogen exchanger 1(NHE1)protein in thoracic aorta was detected by immunohistochemistry.Results Compared with the control group,the NO level and SOD activity in the serum of mice in the AS group decreased,while the MDA level increased(P＜0.05);there was no significant difference in the NO,MDA levels and SOD activity in the serum of mice between the VB6 group and the control group(P＞0.05).Compared with the AS group,the serum NO level and SOD activity of mice in the AS+VB6 group increased,while the MDA level decreased(P＜0.05);there was no significant difference in serum NO,MDA levels and SOD activity of mice between the AS+LiCl group,AS+VB6+LiCl group and AS group(P＞0.05).Compared with the AS+VB6 group,the serum NO level and SOD activity of mice in the AS+VB6+LiCl group decreased,while the MDA level increased(P＜0.05).The percentage of AS plaque area to total vascular area of mice in the AS group was significantly higher than that in the control group(P＜0.05);there was no significant difference in the percentage of AS plaque area to total vascular area of mice among the VB6 group and the control group(P＜0.05).The percentage of AS plaque area to total vascular area of mice in the AS+VB6 group was significantly lower than that in the AS group(P＜0.05);there was no significant difference in the percentage of AS plaque area to total vascular area of mice between the AS+LiCl group,AS+VB6+LiCl group and AS group(P＜0.05).The percentage of AS plaque area to total vascular area of mice in the AS+VB6+LiCl group was significantly higher than that in the AS+VB6 group(P＜0.05).In the control group,the vascular endothelium of mice was smooth with orderly arrangement of cells;in the AS group,AS+LiCl group and AS+VB6+LiCl group,the tissue structure of vascular of mice was disordered and the vascular endothelium was rough;in the VB6 group and AS+VB6 group,the vascular wall structure of mice was normal,the vascular endothelium was smooth,and the cells were arranged orderly.The vasodilatation rate of thoracic aorta of mice induced by acetylcholine(Ach)in the AS group was significantly lower than that in the control group(P＜0.05);there was no significant difference in the vasodilatation rate of thoracic aorta of mice induced by Ach between the VB6 group and the control group(P＞0.05).The vasodilatation rate of thoracic aorta of mice induced by Ach in the AS+VB6 group was significantly lower than that in the AS group(P＜0.05);there was no significant difference in the vasodilatation rate of thoracic aorta of mice induced by Ach between AS+LiCl group,AS+VB6+LiCl group and AS group(P＞0.05).The vasodilatation rate of thoracic aorta of mice induced by Ach in the AS+VB6+LiCl group was significantly higher than that in the AS+VB6 group(P＜0.05).There was no significant difference in the vasodilatation rate of thoracic aorta of mice induced by sodium nitroprusside among the six groups(P＞0.05).The percentage of NHE1 expression in the thoracic aorta of mice in the AS group was significantly higher than that in the control group(P＜0.05);there was no significant difference in the percentage of NHE1 expression in the thoracic aorta of mice between the VB6 group and the control group(P＞0.05).The percentage of NHE1 expression in the thoracic aorta of mice in the AS+VB6 group was significantly lower than that in the AS group(P＜0.05);there was no significant difference in the percentage of NHE1 expression in the thoracic aorta of mice among the AS+LiCl group,AS+VB6+LiCl group and the AS group(P＞0.05).The percentage of NHE1 expression in the thoracic aorta of mice in the AS+VB6+LiCl group was significantly higher than that in the AS+VB6 group(P＜0.05).Conclusion VB6 can improve vascular endothelial injury in AS mice via inhibiting the expression of NHE1 protein.

Objective To evaluate the value of miniprobe endoscopic ultrasound(EUS)in guiding endoscopic treatment of small-diameter(maximum diameter less than 1 cm)and low-grade(G1 grade)rectum neuroendocrine neoplasm(R-NEN),and to provide evidence and clues for its clinical application and further research.Methods The clinical data of 85 cases of low-grade(G1 grade)R-NEN with a maximum diameter of less than 1 cm who underwent endoscopic treatment in our center from January 2014 to December 2020 were retrospectively analyzed.The patients were divided into the EUS group(37 cases)and control group(48 cases)according to whether EUS was performed before endoscopic treatment.The positive rate of incision margin,the incidence of complications,the recurrence rate,the hospital stay,the cost of hospitalization and endoscopic therapy were compared between the two groups.Results The positive rate of incision margin in the EUS group was significantly lower than that in control group(P<0.05).There was no significant difference in the incidence of complications,tumor recurrence rate,hospital stay or hospital costs between the two groups(P>0.05).There was statistically significant difference in the endoscopic therapy between the two groups(P<0.05).Conclusion Evaluating the lesion depth of small-diameter and low-grade(G1 grade)R-NEN before surgery by miniprobe EUS and selecting endoscopic surgery according to its results of can significantly reduce the residual risk of resection margin tumors.

Objective:To explore the research hotspots and effective promotion paths of post market surveillance and supervise of medical consumables with non-active medical devices.Methods:Data mining methods were used to collect related journal literatures and documents from the websites of China regulatory institutions and the China National Knowledge Infrastructure(CNKI),order sub item data of medical device adverse event reports,extract the MeSH element words of literatures and documents,perform bibliometric analysis and visual display.Results:The number of medical devices adverse event reports in China has been increasing year by year,reaching 694 866 in 2022,in the four statistical years from 2019 to 2022,the number of reports on non-active medical devices and IVD reagents also showed a parallel increasing trend,accounting for about 65.00% of the total number of adverse event reports on medical devices in the year.The bibliometric analysis of journal literature shows that research in this field has received varying degrees of participation from regulatory institutions,universities,medical institutions,and enterprises.Regulatory institutions have contributed 46 articles,accounting for 56.79% of the total number of articles,followed by 28 articles from universities.The co-occurrence analysis shows that hot topic is focused in 5 clusters:quality management,risk management,international experiences discussion and adverse event surveillance and re-evaluation and real-world research.China regulatory institutions attach great importance to post market surveillance and supervise,and have issued more than 20 relevant documents since 2006,focusing on specific topics and gradually deepening around safety and effectiveness.Conclusion:The post market surveillance and supervise of medical devices,especially medical consumables based on non-active medical devices,need to be promoted synchronously in three dimensions:regulatory institutions,medical institutions,and enterprises.Universities,research institutes,and industry organizations should work in coordinating to strengthen the collection,identification,and active surveillance of risk signals based on adverse event surveillance,safety evaluation based on risk management,and conducting real-world research,research and develop risk control and corrective and preventive measures.

The Piezo protein is a non-selective mechanosensitive cation channel that exhibits sensitivity to mechanical stimuli such as pressure and shear stress. It converts mechanical signals into bioelectric activity within cells, thus triggering specific biological responses. In the digestive system, Piezo protein plays a crucial role in maintaining normal physiological activities, including digestion, absorption, metabolic regulation, and immune modulation. However, dysregulation in Piezo protein expression may lead to the occurrence of several pathological conditions, including visceral hypersensitivity, impairment of intestinal mucosal barrier function, and immune inflammation.Therefore, conducting a comprehensive review of the physiological functions and pathological roles of Piezo protein in the digestive system is of paramount importance. In this review, we systematically summarize the structural and dynamic characteristics of Piezo protein, its expression patterns, and physiological functions in the digestive system. We particularly focus on elucidating the mechanisms of action of Piezo protein in digestive system tumor diseases, inflammatory diseases, fibrotic diseases, and functional disorders. Through the integration of the latest research findings, we have observed that Piezo protein plays a crucial role in the pathogenesis of various digestive system diseases. There exist intricate interactions between Piezo protein and multiple phenotypes of digestive system tumors such as proliferation, apoptosis, and metastasis. In inflammatory diseases, Piezo protein promotes intestinal immune responses and pancreatic trypsinogen activation, contributing to the development of ulcerative colitis, Crohn’s disease, and pancreatitis. Additionally, Piezo1, through pathways involving co-action with the TRPV4 ion channel, facilitates neutrophil recruitment and suppresses HIF-1α ubiquitination, thereby mediating organ fibrosis in organs like the liver and pancreas. Moreover, Piezo protein regulation by gut microbiota or factors like age and gender can result in increased or decreased visceral sensitivity, and alterations in intestinal mucosal barrier structure and permeability, which are closely associated with functional disorders like irritable bowel sydrome (IBS) and functional consitipaction (FC). A thorough exploration of Piezo protein as a potential therapeutic target in digestive system diseases can provide a scientific basis and theoretical support for future clinical diagnosis and treatment strategies.

Objective To analyze the risk of adverse drug events in pediatric clinical applications of tocilizumab versus inflixima.Methods Adverse event(AE)reporting data for tocilizumab versus infliximab in the U.S.Food and Drug Administration Adverse Event Reporting System database for the pediatric population from Q1 2013 to Q1 2023 were collected.AE risk signal mining was performed using the reporting odds ratio(ROR)method and the proportional reporting ratio(PRR)method.AEs were also classified and statistically analyzed according to the preferred system organ classification and preferred terminology(PT)of the International Dictionary of Medical Terminology.Results Data were extracted and cleaned to include 1 052 AE reports with 198 positive PT signals for tocilizumab as the suspected drug and 9 1 39 AE reports with 387 positive PT signals for infliximab as the suspected drug.The analyses suggested that the stronger positive risk signals for both drugs were focused on gastrointestinal disorders,infectious and invasive diseases,laboratory tests,musculoskeletal and connective tissue disorders,and blood,vascular,and lymphatic disorders.The risk signals for infliximab were focused on gastrointestinal disorders,infections,and infectious diseases,while the risk signals for tocilizumab were focused on the musculoskeletal muscle system.Conclusion Clinical use of both drugs in children has multi-system effects,tocilizumab may have effects on growth and development,and infliximab has effects on the gastrointestinal tract in children.

[Objective] To investigate the pathological characteristics of false-positive lesions of prostate cancer on ⁶⁸Ga-PSMA-11 PET/CT based on the pathology of whole mount specimens, in order to more accurately assess the degree of malignancy within the prostate tissue and avoid overdiagnosis and unnecessary treatment. [Methods] A total of 77 patients who underwent ⁶⁸Ga-PSMA-11 PET/CT before radical prostatectomy in Nanjing Drum Tower Hospital during Jan.2018 and Dec.2022 were retrospectively analyzed.The pathology of whole mount specimens was detected.Two nuclear physicians examined all imaging plates without knowing the pathological results.Two pathological physicians completed all pathological diagnosis without knowing the imaging results.The pathological characteristics of false-positive lesions were determined by matching ⁶⁸Ga-PSMA-11 PET/CT and pathological specimens.To analyze the pathological features of false-positive lesions, true-negative lesions were randomly delineated and defined.The pathological features of false-positive and true-negative lesions were analyzed and compared using Fisher exact test. [Results] After the imaging and pathological sections were matched, 21(16.3%) false-positive lesions were identified.The pathological characteristics of the 21 false-positive lesions were as follows: 16 (76.2%) simple atrophy with cyst formation, 3(14.3%) prostatic nodular hyperplasia, and 2(9.5%) inflammation.The pathological characteristics of 21 true-negative lesions were: 13(61.9%) normal glands, 5(23.8%) prostatic nodular hyperplasia and 3(14.3%) simple atrophy with cyst formation.Fisher exact test showed that the proportion of simple atrophy with cyst formation in the pathological features of false-positive lesions and true-negative lesions was statistically significant (76.2% vs.14.3%, P<0.001). [Conclusion] Simple atrophy with cyst formation may be a characteristic pathological type of the false-positive lesions of prostate cancer on ⁶⁸Ga-PSMA-11 PET/CT.

Objective:To investigate the effect of tocilizumab (TCZ) on ventricular arrhythmias (VAs) after myocardial infarction (MI) in Sprague-Dawley rats and explore its potential mechanism.Methods:The random number table method was used to divide 32 adult male Sprague-Dawley rats into 4 groups: Sham group, TCZ group, MI group and MI+TCZ group, with 8 rats in each group. The MI model was established by ligation of the left anterior descending branch of the coronary artery in the MI and MI+TCZ groups, and only sutured without ligation in the Sham and TCZ groups. TCZ was injected into the left superior cervical ganglion (SCG) of rats in the TCZ and MI+TCZ groups after successful modeling or sham operation, and the same amount of normal saline was injected in the Sham and MI groups. 24 h after successful modeling, ECG of rats in each group was recorded, heart rate variability (HRV, including low frequency power (LF), high frequency power (HF), LF/HF ratio), QT interval, QTc interval were calculated, and left ventricular effective refractory period (ERP) and VA inducibility were measured. Myocardial infarct size and tissue changes were observed with triphenyl tetrazolium chloride staining and HE staining. Real-time PCR analysis was used to detect the messager RNA (mRNA) expression of interleukin-6 (IL-6) and signal transducer and activator of transcription (STAT) 3 in SCG and potassium voltage-gated channel subfamily D member 2 (Kcnd2) in myocardial infarction periphery. The expression of c-fos in SCG was detected by immunofluorescence staining.Results:Compared with Sham group and MI+TCZ group, rats in MI group had higher LF and LF/HF ratio, longer QT interval and QTc interval, more VAs induced, lower HF and shorter ERP ( P all<0.05). Triphenyl tetrazolium chloride staining and HE staining showed that rats in the Sham and TCZ groups had normal myocardial tissue structure, those in the MI group had severe myocardial injury, and those in the MI+TCZ group had less myocardial injury than those in the MI group. Real-ime PCR analysis showed that compared with Sham group and MI+TCZ group, mRNA expression levels of IL-6 and STAT3 in SCG of rats in MI group were higher, and mRNA expression level of myocardial Kcnd2 was lower ( P all<0.05). Immunofluorescence staining showed that the content of c-fos in SCG of rats in MI group was higher than that of Sham group and MI+TCZ group ( P all<0.05). Conclusions:TCZ may reduce neural activity of the SCG after MI by inhibiting the IL-6/STAT3 signaling pathway, thereby alleviating myocardial injury and inhibiting VAs.