AIM: To develop a novel gene-delivery therapeutic based on CRISPR/Cas9 genome editing technology capable of specifically targeting and knocking out the VEGFA gene, thereby achieving sustained suppression of VEGFA expression in retinal pigment epithelial(RPE)cells and providing a new strategy for gene therapy in retinal neovascular diseases.METHODS:Single guide RNAs targeting the human VEGFA gene for knockout were designed, and corresponding recombinant plasmids were constructed. A novel polymer(PTEE)was used to encapsulate the plasmids to prepare a PTEE-loaded anti-VEGFA plasmid(PLAP)gene delivery system. PTEE materials at concentrations of 0.1, 0.2, 0.4, 0.8, and 1.6 μg/μL were co-incubated with ARPE-19 cells, and the biocompatibility of PTEE was evaluated using the cell counting kit-8(CCK-8)assay. Recombinant plasmids expressing green fluorescent protein(GFP)were constructed. Lipofectamine 3000 and jetOPTIMUS®DNA transfection reagents were used as control groups, and PTEE nanomaterials were used as the experimental group to encapsulate the plasmids. When the cell confluence reached 80%, the formulations were transfected into ARPE-19 and 293T cells. GFP expression was observed under light microscopy, and the transfection efficiencies of each group were compared. ARPE-19 cells were induced under hypoxia, and PLAP was transfected into the cells. The expression level of VEGFA was detected by enzyme-linked immunosorbent assay(ELISA)to evaluate the efficacy of this novel gene delivery system.RESULTS: After co-incubation of ARPE-19 cells with different concentrations of PTEE for 24 h and 48 h, no significant effect on cell viability was observed in any group. The transfection efficiency of PLAP in ARPE-19 cells was higher than that in the Lipo3000 and jetOPTIMUS groups, with statistically significant differences(P<0.01). Hypoxia for 6 h significantly induced the upregulation of VEGFA mRNA expression in ARPE-19 cells, and under hypoxic conditions, the PTEE group exhibited a significant inhibitory effect on VEGFA expression(P<0.01).CONCLUSION:PLAP exhibits favorable biocompatibility and prominent VEGFA inhibitory effects in vitro, making it a potential candidate drug for gene therapy of retinal neovascular diseases.

Sj?gren's syndrome(SS)is one of the common rheumatic diseases in clinical practice.Modern medicine commonly uses drugs such as artificial tears,saliva,glucocorticoids,immunosuppressants,and biologics to control the condition.Clinical practice has shown that in addition to modern medical basic treatment,the use of traditional Chinese medicine(TCM)can help improve the clinical efficacy of SS.According to the symptoms and signs of Sj?gren's syndrome in TCM,it is classified as"dryness and obstruction",and the core pathogenesis of the disease is spleen deficiency and deficiency of body fluids.Subsequently,toxic and pathogenic factors gather,leading to the decline of internal organs.The initial causes are spleen damage,unstable barrier,and invasion of pathogenic factors.The core link is spleen dysfunction,insufficient body fluid,and dryness arising from it.Spleen deficiency generates evil,obstruction of qi,and lack of body fluids are the root causes of illness.The main treatment method is the"spleen strengthening method",which treats spleen deficiency,dampness and stagnation,and the body fluid is not distributed.The treatment focuses on strengthening the spleen and qi,supplementing the lungs and generating fluids.Spleen deficiency leads to loss of vitality,blood stasis obstructs blood vessels,and the treatment is to strengthen the spleen,soothe the liver,remove blood stasis,and unblock the orifices.The spleen yang is not vigorous,and qi transformation is impaired.The treatment is to invigorate the spleen and warm the stomach,promote yang circulation,and promote diuresis.

Objective:To evaluate the repeatability of anterior segment biometry measurements obtained using ultrasound biomicroscopy (UBM) and the ArcScan Insight 100, and to compare the agreement between the two devices.Methods:A cross-sectional study was conducted.Seventy myopic patients (70 eyes) who underwent V4c implantable collamer lens implantation at Henan Eye Hospital from March to May 2023 were included.The ArcScan Insight 100 and UBM were used to measure the following parameters three times: angle-to-angle distance (ATA), sulcus-to-sulcus distance (STS), anterior chamber depth (ACD), crystalline lens rise (CLR), anterior chamber width (ACW), ciliary body inner diameter (CBID), anterior chamber angle (ACA), trabecular-ciliary angle (TCA) and maximum ciliary body thickness (CBTmax). The repeatability of anterior segment biological measurements obtained using the two devices was assessed by intraclass correlation coefficient (ICC). The consistency between the two instruments was evaluated by Bland-Altman consistency test.This study complied with the Declaration of Helsinki and was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECKY-2021[13]). All patients understood the purpose and significance of this study and signed the informed consent form.Results:The repeatability of ATA, STS, ACD, CLR, ACW, CBID, ACA, TCA and CBTmax measured by UBM and ArcScan Insight 100 was good (all ICC>0.9). There was no significant difference in ACD, ACW, and ACA between the two instruments ( t=0.696, -1.025, -1.447; all P>0.05). ATA, STS, CLR and CBID measured by UBM were lower and TCA and CBTmax were higher than those measured by UBM ArcScan Insight 100, and the differences were statistically significant ( t=-8.586, -12.551, -4.481, -4.420, 4.535, 7.812; all P<0.05). The differences of ATA, STS, ACD, CLR, ACW, CBID and CBTmax between UBM and ArcScan Insight 100 were 0.38, 0.47, -0.01, 0.07, 0.3, 0.26 and -0.21 mm, respectively, with the 95% limits of agreement (LoA) of (-0.34, 1.10), (-0.15, 1.09), (-0.28, 0.26), (-0.20, 0.35), (-0.33, 0.93), (-0.71, 1.23) and (-0.64, 0.23)mm, respectively, which showed good coherence.The differences in ACA and TCA measurements were 2.26° and -7.81°, respectively, and the 95%LoA values were (-23.36°, 27.89°) and (-36.05°, 20.43°), respectively, with poor coherence.There was a strong positive correlation in ACD measurements measured by UBM and ArcScan Insight 100 ( r=0.827, P<0.05). There were moderate positive correlations in ATA, STS, CLR, ACW and CBID ( r=0.678, 0.749, 0.617, 0.765, 0.519; all P<0.05). There was no significant correlation in ACA, TCA and CBTmax ( r=0.270, 0.032, 0.178; all P>0.05). Conclusions:The repeatability of ArcScan Insight 100 and UBM in measuring anterior segment biological parameters is good.However, the consistency of ACA, TCA and CBTmax measured by the two instruments is poor and may be affected by self-regulation of the body.ATA, STS, ACD, CLR, ACW and CBID have good consistency and can be used interchangeably.

In recent years,using digital health technology can improve the quality and effect of nutrition management for patients with gestational diabetes mellitus(GDM).This article provides an overview of digital health technology,reviews the application form and effect of digital health technology in nutrition manage-ment of pregnant women with GDM,puts forward suggestions,in order to provide references and bases for promoting the more scientific,effective and standardized application of digital health technology in nutrition management of GDM patients.

Objective:To evaluate the repeatability of anterior segment biometry measurements obtained using ultrasound biomicroscopy (UBM) and the ArcScan Insight 100, and to compare the agreement between the two devices.Methods:A cross-sectional study was conducted.Seventy myopic patients (70 eyes) who underwent V4c implantable collamer lens implantation at Henan Eye Hospital from March to May 2023 were included.The ArcScan Insight 100 and UBM were used to measure the following parameters three times: angle-to-angle distance (ATA), sulcus-to-sulcus distance (STS), anterior chamber depth (ACD), crystalline lens rise (CLR), anterior chamber width (ACW), ciliary body inner diameter (CBID), anterior chamber angle (ACA), trabecular-ciliary angle (TCA) and maximum ciliary body thickness (CBTmax). The repeatability of anterior segment biological measurements obtained using the two devices was assessed by intraclass correlation coefficient (ICC). The consistency between the two instruments was evaluated by Bland-Altman consistency test.This study complied with the Declaration of Helsinki and was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECKY-2021[13]). All patients understood the purpose and significance of this study and signed the informed consent form.Results:The repeatability of ATA, STS, ACD, CLR, ACW, CBID, ACA, TCA and CBTmax measured by UBM and ArcScan Insight 100 was good (all ICC>0.9). There was no significant difference in ACD, ACW, and ACA between the two instruments ( t=0.696, -1.025, -1.447; all P>0.05). ATA, STS, CLR and CBID measured by UBM were lower and TCA and CBTmax were higher than those measured by UBM ArcScan Insight 100, and the differences were statistically significant ( t=-8.586, -12.551, -4.481, -4.420, 4.535, 7.812; all P<0.05). The differences of ATA, STS, ACD, CLR, ACW, CBID and CBTmax between UBM and ArcScan Insight 100 were 0.38, 0.47, -0.01, 0.07, 0.3, 0.26 and -0.21 mm, respectively, with the 95% limits of agreement (LoA) of (-0.34, 1.10), (-0.15, 1.09), (-0.28, 0.26), (-0.20, 0.35), (-0.33, 0.93), (-0.71, 1.23) and (-0.64, 0.23)mm, respectively, which showed good coherence.The differences in ACA and TCA measurements were 2.26° and -7.81°, respectively, and the 95%LoA values were (-23.36°, 27.89°) and (-36.05°, 20.43°), respectively, with poor coherence.There was a strong positive correlation in ACD measurements measured by UBM and ArcScan Insight 100 ( r=0.827, P<0.05). There were moderate positive correlations in ATA, STS, CLR, ACW and CBID ( r=0.678, 0.749, 0.617, 0.765, 0.519; all P<0.05). There was no significant correlation in ACA, TCA and CBTmax ( r=0.270, 0.032, 0.178; all P>0.05). Conclusions:The repeatability of ArcScan Insight 100 and UBM in measuring anterior segment biological parameters is good.However, the consistency of ACA, TCA and CBTmax measured by the two instruments is poor and may be affected by self-regulation of the body.ATA, STS, ACD, CLR, ACW and CBID have good consistency and can be used interchangeably.

In recent years,using digital health technology can improve the quality and effect of nutrition management for patients with gestational diabetes mellitus(GDM).This article provides an overview of digital health technology,reviews the application form and effect of digital health technology in nutrition manage-ment of pregnant women with GDM,puts forward suggestions,in order to provide references and bases for promoting the more scientific,effective and standardized application of digital health technology in nutrition management of GDM patients.

Sj?gren's syndrome(SS)is one of the common rheumatic diseases in clinical practice.Modern medicine commonly uses drugs such as artificial tears,saliva,glucocorticoids,immunosuppressants,and biologics to control the condition.Clinical practice has shown that in addition to modern medical basic treatment,the use of traditional Chinese medicine(TCM)can help improve the clinical efficacy of SS.According to the symptoms and signs of Sj?gren's syndrome in TCM,it is classified as"dryness and obstruction",and the core pathogenesis of the disease is spleen deficiency and deficiency of body fluids.Subsequently,toxic and pathogenic factors gather,leading to the decline of internal organs.The initial causes are spleen damage,unstable barrier,and invasion of pathogenic factors.The core link is spleen dysfunction,insufficient body fluid,and dryness arising from it.Spleen deficiency generates evil,obstruction of qi,and lack of body fluids are the root causes of illness.The main treatment method is the"spleen strengthening method",which treats spleen deficiency,dampness and stagnation,and the body fluid is not distributed.The treatment focuses on strengthening the spleen and qi,supplementing the lungs and generating fluids.Spleen deficiency leads to loss of vitality,blood stasis obstructs blood vessels,and the treatment is to strengthen the spleen,soothe the liver,remove blood stasis,and unblock the orifices.The spleen yang is not vigorous,and qi transformation is impaired.The treatment is to invigorate the spleen and warm the stomach,promote yang circulation,and promote diuresis.

The development of medical research is completed by the cooperation of sponsors, investigators, subjects, and ethics committees. Clinically, it mainly includes clinical trials of medical devices, clinical medicine and new technology research. This paper analyzed the game and the relationship between rights, responsibilities and interests of relevant parties in medical research, combined with the relevant costs and sharing principles involved in medical research, and found that the use of the word "free" in the informed consent is easy to cause misunderstanding and the lack of relevant compensation costs in the informed consent, while the compensation and insurance costs had some problems, such as the imperfect subject compensation mechanism and the insufficient insurance purchase by the sponsor, which can not protect the basic rights and interests of the subjects. Therefore, in order to standardize the cost management of clinical medical research, it is necessary to standardize the process and content of informed consent, strengthen the supervision of medical research process, establish medical research damage compensation fund and research damage insurance system, so as to better protect the rights and interests of subjects.

Under the "patient-centered" drug regulation concept,the inclusion of patient dimensions in real-world evidence becomes increasingly important. Patient experience data can complement and interpret existing data,generate evidence directly from patients,and achieve patient participation in drug development. Data types include patient-reported outcomes and free-text data,which can be collected autonomously or obtained from databases. Application scenarios involve new drug registration,safety evaluation,and additional indications. In China,applying patient experience data to real-world study mainly faces the following challenges:lack of conditions,standards,and motivation to collect high-quality data,a single type of data,and the difficulty of balancing data security with freedom,etc. It is recommended to issue special guidelines,establish a measurement tool certification process,expand data collection channels,explore data source integration methods,optimize the informed consent mechanism,and establish an evidence synergy mechanism to promote the practical application of the "patient-centered" concept in real-world study of drugs.

As a neurological disorder in the brain, epilepsy is not only associated with abnormal synchronized discharging of neurons, but also inseparable from non-neuronal elements in the altered microenvironment. Anti-epileptic drugs (AEDs) merely focusing on neuronal circuits frequently turn out deficient, which is necessitating comprehensive strategies of medications to cover over-exciting neurons, activated glial cells, oxidative stress and chronic inflammation synchronously. Therefore, we would report the design of a polymeric micelle drug delivery system that was functioned with brain targeting and cerebral microenvironment modulation. In brief, reactive oxygen species (ROS)-sensitive phenylboronic ester was conjugated with poly-ethylene glycol (PEG) to form amphiphilic copolymers. Additionally, dehydroascorbic acid (DHAA), an analogue of glucose, was applied to target glucose transporter 1 (GLUT1) and facilitate micelle penetration across the blood‒brain barrier (BBB). A classic hydrophobic AED, lamotrigine (LTG), was encapsulated in the micelles via self-assembly. When administrated and transferred across the BBB, ROS-scavenging polymers were expected to integrate anti-oxidation, anti-inflammation and neuro-electric modulation into one strategy. Moreover, micelles would alter LTG distribution in vivo with improved efficacy. Overall, the combined anti-epileptic therapy might provide effective opinions on how to maximize neuroprotection during early epileptogenesis.