Gene therapy, harnessing the power of CRISPR-Cas9 and/or DNAzyme systems, stands as a pivotal approach in cancer therapy, enabling the meticulous manipulation of genes pivotal to tumorigenesis and immunity. However, the pursuit of precise gene therapy encounters formidable hurdles. Herein, a near-infrared upconversion theranostic nanomachine is devised and tailors for CRISPR-Cas9/DNAzyme systems mediate precise gene therapy. An ingenious logic DNAzyme system consists of Chain 1 (C1)/Chain 2 (C2) and endogenous lncRNA is designed. We employ manganese modified upconversion nanoparticles for carrying ultraviolet-responsive C1-PC linker-C2 (C₂P) chain and Cas9 ribonucleoprotein (RNP), with outermost coats with hyaluronic acid. Upon reaching tumor microenvironment (TME), the released Mn²⁺ ions orchestrate a trifecta: facilitating endosomal escape, activating cGAS-STING signaling, and enabling T1-magnetic resonance imaging. Under near-infrared irradiation, Cas9 RNP/C₂P complex dissociates, releasing Cas9 RNP into the nucleus to perform gene editing of Ptpn2, while C1/C2 chains self-assemble with endogenous lncRNA to form a functional DNAzyme system, targeting PD-L1 mRNA for gene silencing. This strategy remodels the TME by activating cGAS-STING signaling and dual immune checkpoints blockade, thus realizing tumor elimination. Our theranostic nanomachine armed with the CRISPR-Cas9/DNAzyme logic systems, represents a resourceful and promising strategy for advancing cancer systemic immunotherapy and precise gene therapy.

OBJECTIVES: To investigate the expression of CDKN3 in gastric cancer and its impact on prognosis of gastric cancer patients. METHODS: We analyzed CDKN3 expression in clinical specimens from 114 gastric cancer patients and assessed its association with 5-year postoperative survival of the patients. GO and KEGG enrichment analyses were used to predict the biological function and possible mechanism of CDKN3. The effects of lentivirus-mediated CDKN3 knockdown on biological behaviors of gastric cancer cells were evaluated using Transwell assay, CCK-8 assay, TUNEL staining, flow cytometry, and Western blotting. RESULTS: CDKN3 expression was significantly higher in gastric cancer tissues than in the adjacent tissues with significant correlations with CEA level, CA19-9 level, and T and N staging (P<0.05). High CDKN3 expression was an independent risk factor affecting 5-year postoperative survival of the patients and predictive for long-term prognosis (P<0.01). Enrichment analyses suggested a probable association of CDKN3 with apoptosis. In MGC-803 cells, CDKN3 knockdown significantly lowered migration and invasion capacities of the cells, while CDKN3 overexpression produced the opposite effects. TUNEL staining revealed a significantly lower level of cell apoptosis in gastric cancer tissues than in adjacent tissues (P<0.01). CDKN3 knockdown obviously inhibited proliferation and increased apoptosis of MGC-803 cells. CDKN3 overexpression down-regulated the expressions of p53, p21 and Bax and up-regulated the expressions of p-p65 and Bcl-2. CONCLUSIONS CDKN3 is highly expressed in gastric cancer tissues and affects patient prognosis. CDKN3 overexpression promotes proliferation, invasion and migration and suppressed apoptosis of gastric cancer cells possibly through the p53/NF-κB signaling pathway.
Humans ; Stomach Neoplasms/pathology* ; Apoptosis ; Signal Transduction ; Tumor Suppressor Protein p53/metabolism* ; Cell Movement ; Cell Line, Tumor ; NF-kappa B/metabolism* ; Prognosis ; Cyclin-Dependent Kinase Inhibitor Proteins/metabolism* ; Cell Proliferation ; Neoplasm Invasiveness ; Male ; Female ; Dual-Specificity Phosphatases

Objective To investigate the efficacy and safety of Linaclotide combined with Simethicone oil and compound polyethylene glycol electrolyte(PEG)for cleansing effect of bowel in patients with constipation.Methods A prospective randomized controlled trial was designed and implemented by single blind method.383 patients with constipation who underwent colonoscopy from April 2023 to August 2024 were enrolled and randomly divided into routine group(128 cases),experimental group A(128 cases)and experimental group B(127 cases).Routine group treated with 3 L PEG,experimental group A treated with 290 μg Linaclotide+2 L PEG and experimental group B treated with 290 μg Linaclotide+30 mL Simethicone+2 L PEG.Bowel preparation effect[Boston bowel preparation scale(BBPS)scores and foaming removal effect],lesion detection rate,first defecation interval,frequency of defecation,the success rate of cecal intubation,the insertion time of colonoscopy,the withdrawal time of colonoscopy,incidence of adverse reactions and willingness to repeat examination of the three groups were compared.Results No statistically significant differences were observed in the BBPS scores among the three groups(P>0.05);The foaming removal effect score in experimental group B was significantly lower than that in routine group and experimental group A,the difference was statistically significant(P<0.05);The total lesion detection rate and polyps detection rate of experimental group B were significantly higher than those of routine group and experimental group A,the differences were statistically significant(P<0.05).The first defecation interval of the routine group was significantly longer than that of experimental group A and experimental group B,the difference was statistically significant(P<0.05);The frequency of defecation was compared among the three groups,and the difference was no statistically significant(P>0.05).The success rate of cecal intubation in the three groups was 100.0%,and the insertion time of colonoscopy was similar,the differences were not statistically significant(P>0.05);The withdrawal time of colonoscopy in experimental group B was significantly shorter than that in routine group and experimental group A,the difference was statistically significant(P<0.05).The incidence of abdominal distension and total adverse reactions in the routine group were higher than those in experimental group A and experimental group B,the differences were statistically significant(P<0.05);The willingness to repeat examination rate of the routine group was significantly lower than that of experimental group A and experimental group B,the differences were statistically significant(P<0.05).Conclusion 290 μg Linaclotide combined with 30 mL Simethicone and 2 L PEG solution regimen has advantages in intestinal preparation for patients with constipation,and can achieve better intestinal cleaning effect than 3 L PEG solution and 290 μg linalopeptide+2 L PEG solution regimen,with higher safety and willingness to repeat examination.It can be recommended for bowel preparation for patients with constipation.

Objective:To construct a platform for quality control and performance management of medical equipment based on edge computing architecture,and connect the existing information systems of hospital to achieve interconnection and interworking of bottom layer architecture of medical equipment.Methods:By deeply integrating 5 generation(5G)communication technique and Internet of Things(IoT)technique,and using edge computing architecture,a platform for quality control and performance management of medical equipment was constructed through collected the data of operational log from large-scale medical equipment.A total of 27 medical equipment in clinical use at the Affiliated Wuxi People's Hospital of Nanjing Medical University were selected in the study periods from July to December 2022(pre-implementation phase)and from July to December 2023(post-implementation phase).The accuracy rates of recorded data about equipment's operation were calculated as statistical method before and after the platform was applied.The response times for maintenance,the rates of opening equipment,and frequencies of repairing equipment for computed tomography(CT)equipment were compared between before and after the platform was applied.Results:The platform's primary functions for quality control and performance management of medical equipment mainly encompassed asset ledger,early warning for operation and maintenance,operational dynamics,allocation management,evaluation for usage efficiency,and evaluation for quality control for large-scale medical equipment of hospital.After the platform was applied,the accuracy of recorded data of 27 medical equipment was increased to 97%from 70-80%before the platform was applied.For CT equipment,the average response time and frequency of maintenance after the platform was applied were significantly lower than those before it was applied,while the average rate of opening equipment was significantly higher than that before it was applied,and the differences were significant(t=7.084,3.196,2.537,P<0.05).Conclusion:The platform for quality control and performance management of medical equipment based on edge computing architecture can provide safeguards for the operational quality and safety of large-scale medical equipment,and provide basis for fine using evaluation and rational configuration decisions,and reduce response times and frequency of maintaining equipment,and improve rate of opening equipment,and realize standardization,informatization,and scientificization of the management for large-scale medical equipment.

The spread of antibiotic resistance genes(ARGs)poses a serious threat to global public health.Recent studies have shown that in addition to the difficulty in antibiotic selection,many non-anti-biotic environmental pollutants,such as microplastics,heavy metals,nanomaterials and non-antibiotic drugs,can accelerate the spread of ARGs.This paper begins by outlining the influence of non-antibiotic environmental pollutants on the conjugative transfer of ARGs.Then,the mechanisms of ARGs are analyzed from the perspective of molecular biology,which include inducing the generation of large amounts of reactive oxygen radicals,triggering cellular oxidative stress,increasing intercellular contact,altering the permeability of cell membranes,affecting energy metabolism,triggering group sensing effects,and regulating the expression of genes related to the transfer of ARGs.Finally,the limitations of current studies are presented,and tips are given about future research.In conclusion,the effects of non-antibi-otic environmental pollutants on the spread and dispersal of ARGs need to be studied more extensively.

Objective:To investigate the differences of the glymphatic system (GS) function between patients with mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE-HS) and healthy controls and between different seizure types by using diffusion tensor imaging along perivascular space (DTI-ALPS), and to analyze the correlation between GS function and the course of disease, as well as the efficacy of predicting the surgical outcome.Methods:This study was a cross-sectional study. A total of 171 patients with mTLE-HS (mTLE-HS group) and 75 healthy volunteers (HC group) were retrospectively enrolled from July 2009 to July 2021 at Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University. The general information of all subjects, such as seizure type (partial seizure, secondary generalized seizure), surgical outcome, etc., was analyzed. The 3D magnetization prepared rapid gradient echo T 1WI and DTI sequence images were collected. The VBM analysis method was used to segment cerebrospinal fluid and calculate the volume. The ALPS index of the bilateral brain was calculated using the Atlas-based DTI-ALPS method. Independent sample t-test or paired t test were used to compare the ALPS index between the mTLE-HS group and HC group, and between patients with different seizure types. Pearson correlation analysis was used to analyze the correlation between bilateral ALPS index and disease duration in mTLE-HS group. The predictive value of the ALPS index for surgical outcomes was evaluated by receiver operating characteristics curve and area under the curve. Results:Among the 171 mTLE-HS patients, 98 patients were mTLE with left-side HS (mTLE-LHS) and 73 patients were mTLE with right-side HS (mTLE-RHS); 37 patients underwent surgical treatment, including 27 with good prognosis and 10 with poor prognosis. Compared with the HC group, the left-side ALPS index of mTLE-LHS and mTLE-RHS were both decreased ( P<0.05). The right-side ALPS index in mTLE-RHS was lower than that in the HC group ( P<0.001). There was no significant difference in the right-side ALPS index between mTLE-LHS and HC group ( P=0.080). The ALPS index on the affected side of patients with secondary generalized seizures was significantly lower than that of patients with only partial seizures (all P<0.05), but the difference in ALPS index on the healthy side was not statistically significant( P>0.05). The left-side and right-side ALPS index in mTLE-LHS were negatively correlated with disease duration ( r=-0.272, P=0.007; r=-0.307, P=0.002), but no significant correlation was found between the left-side or right-side ALPS index in mTLE-RHS (all P>0.05). The DTI-ALPS index on the affected side in mTLE-HS patients exhibited good diagnostic accuracy for surgical outcome classification, with an area under the curve of 0.778. Conclusions:The patients with mTLE-HS exhibit dysfunction of the GS, and the degree of impairment is related to the type of seizure and the course of epilepsy. The ALPS index, which characterizes the function of GS, demonstrates good diagnostic accuracy for classifying surgical outcomes.

Objective:To compare the efficacy of body posture combined with pharmacotherapy and pharmacotherapy alone in the treatment of chronic subdural hematoma(CSDH).Methods:Firstly, retrospective case series study was conducted. Thirty cases of CSDH that had received body posture combined with pharmacotherapy at Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University from December 2016 to October 2020 were studied retrospectively. Twenty-seven patients were male, and 3 patients were female. The age of patients ( M(IQR)) was 66(16) years (range:28 to 84). Nineteen patients had unilateral hematoma, and 11 patients had bilateral hematoma. All patients received pharmacotherapy and body posture therapy that was to raise their lower limbs 20 to 30 cm with leg lift pad and get abdominal compressed with customized abdominal belt in supine position. Patients were required to maintain the body posture as much as possible, with the maximum to 16 to 18 hours per day. Patients with unilateral hematoma should tilt the head to the affected side and avoid tilting it to the opposite side. For patients with bilateral hematoma, there was no need for head lateralization. Patient were treated with oral dexamethasone and atorvastatin simultaneously. The preliminary efficacy of body posture combined with pharmacotherapy was determined by hematoma improvement rate which was analyzed by Clopper-Pearson method. Then, the multi-center, prospective, randomized controlled trial had carried out in 9 medical centers from August 2020 to November 2021. The stratified block randomization method was adopted. Patients were randomized in a ratio of 1∶1 to either receive pharmacotherapy alone(the control group) or body posture combined with pharmacotherapy(the experiment group) for 3 months and followed up for 6 months. Effective treatment was defined as complete absorption of hematoma, or the hematoma volume decreased by more than 10 ml and Markwalder grading scale score had improved by more than 1 point compared to the baseline. The efficacy rate and surgery conversion rate at 3 months and recurrence at 6 months were observed. Comparison between groups was performed with paired sample t test, Mann-Whitney U test, χ2 test, corrected χ2 test, or Fisher exact probability method. Logistic regression was used to compare the effective rate and operation rate between the two groups. Results:In the respective study, 30 patients completed follow-up 13 to 353 days after treatment. At the last follow-up, the incidence of almost complete absorption or significantly absorption of hematoma (hematoma volume was significantly reduced accompanied by symptom improvement) was 93.3%. The 95% CI for the incidence that analyzed by the Clopper-Pearson method was 77.9% to 99.2%. One hundred and six patients were enrolled in the multicenter study. Fifty-five patients underwent body posture combined with pharmacotherapy. The age was 74(17) years (range:26 to 92). Thirty-nine patients were males and 16 were females. Fifty-one patients underwent pharmacotherapy alone. The age was 69(12) years (range:48 to 84). Thirty-seven patients were males and 14 were females. The length of body posture recorded in diary card was (15.7±2.3) hours(range:7.6 to 19.3 hours). The efficacy rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 83.6% (46/55) and 56.9% (29/51), respectively at 3 months. The result of the logistic regression analysis showed that the efficacy of body posture combined with pharmacotherapy group was better than that of pharmacotherapy alone group ( OR=3.88,95% CI:1.57 to 9.58, P=0.003). Surgery rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 5.5% (3/55) and 21.6% (11/51) respectively. The result of Logistic regression showed that the pharmacotherapy alone group was more likely to be converted to surgery ( OR=0.21,95% CI:0.05 to 0.80, P=0.023). At the 6 months, no recurrence of cases was found in the body posture combined with pharmacotherapy group. However, the recurrence rate of pharmacotherapy alone group was 6.3% (3/48), there was no significant difference between the two groups ( P>0.05). Conclusion:The effect of body posture combined with pharmacotherapy for chronic subdural hematoma is better than that of pharmacotherapy alone.

Cell-free biosensors are detection tools that involve cell-free protein synthesis and consist of recognition elements and reporting elements.These biosensors offer several advantages,such as the ease of construction,a significant specificity and a high sensitivity.By overcoming the limitations associated with cell survival and cell membrane barriers,cell-free biosensors can considerably reduce response times.This article reviewed the recognition and reporting compo-nents of cell-free biosensors,summarizes recent research advancements in their applications to such spheres of public health as environmental monitoring and disease diagnosis,and explores the programmability and logical analysis capabili-ties of these biosensors.Future developments in this field are also predicted.

With the increasing abuse of antibiotics,the development of rapid,accurate and sensitive methods for antibiotic detection has become critical.Nucleic acid sensors as new biosensors have shown great potential in the field of antibiotic detection due to their high selectivity,high sensitivity and real-time monitoring ability.This paper reviews the research progress in antibiotic detection based on nucleic acid sensors,including colorimetric,optical and electrochemical nucleic acid sensors,in the hope of providing a reference for the research and development of new types of antibiotic detection technologies based on nucleic acid sensors.

Objective To evaluate the efficacy and safety of Jiawei Dihuang Decoction in the treatment of vascular dementia(VD);To explore its mechanism and the VD susceptibility genesby using whole exome sequencing.Methods A total of 75 patients with VD who were hospitalized or received outpatient treatment at The Second Affiliated Hospital of Shaanxi University of Chinese Medicine were included.They were divided into the control group(37 cases,treated with conventional Western medicine)and the experimental group(38 cases,treated with conventional Western medicine+Jiawei Dihuang Decoction)using random number table method.The treatment course was 3 months.The general data,TCM syndrome scores,MMSE scores,ADL scores,Blessed scores and adverse reactions of the two groups were compared.Peripheral blood samples from 36 patients with kidney-yin deficiency type VD were selected for whole exome sequencing.Susceptible genes were screened,and the targets of Jiawei Dihuang Decoction were analyzed by network pharmacology.A"drug-gene"network was constructed,and key pathways were enriched.Results There was no statistical significance in the baseline data between the two groups(P>0.05),and they were comparable.Compared with before treatment,the MMSE scores of patients in both groups significantly increased after treatment,while TCM syndrome scores and ADL scores significantly decreased(P<0.05).Compared with the control group,the TCM syndrome scores,MMSE scores,ADL scores and clinical efficacy of the experimental group were significantly better than those of the control group(P<0.05).Moreover,the Blessed score showed that the experimental group had more advantages in improving the patients'living ability and daily habits(P<0.05).No adverse reactions were observed in both groups during the treatment period.A total of 1 250 744 single nucleotide polymorphism(SNP)loci and 37 314 insertion and deletion(InDel)loci were detected by whole exome sequencing.After screening,3 041 VD susceptibility genes were obtained.It was found that they were involved in biological processes such as the response to nutrient levels,positive regulation of the MAPK cascade,vascular processes in the circulatory system,the response to nutrients,etc.And enriched in PI3K-Akt,cholinergic/glutamatergic synapses,lipid metabolism and atherosclerosis pathways.The potential targets of 854 of Jiawei Dihuang Decoction were intersected with the susceptibility genes to obtain 353 common targets.The top 10 key genes were analyzed and found to be involved in positive regulation of cytosine-serine phosphorylation,miRNA-mediated gene silencing regulation,and the response of cells to decreased oxygen levels,etc.They were enriched in PI3K-Akt,lipid and atherosclerosis signaling pathways.Conclusion Jiawei Dihuang Decoction can alleviate the symptoms of patients with VD,protect cognitive function,enhance their ability of daily living,and has good safety profile.Its mechanism may involve regulating susceptibility genes through PI3K-Akt signaling pathway and lipid atherosclerosis signaling pathway,and improving lipid metabolism,inflammatory response and oxidative stress.