OBJECTIVE To optimize the management model of drugs used in investigator-initiated trial （IIT）. METHODS With benchmarking analysis， based on the practical work experience of a tertiary specialized hospital in the field of IIT drug management in Shanghai， a thorough review was conducted， involving relevant laws， regulations， and academic literature to establish benchmark criteria and the evaluation standards. Starting from the initiation of IIT projects， a detailed comparative analysis of key processes was carried out， such as the receipt， storage， distribution， use and recycling of drugs for trial. The deficiencies in the current management of IIT drugs were reviewed in detail and a series of optimization suggestions were put forward. RESULTS It was found that the authorized records of drug management were missing， the training before project implementation was insufficient， and the records of receipt and acceptance of IIT drugs were incomplete. In light of these existing problems， improvement measures were put forward， including strengthening the training of drug administrators and stipulating that only drug administrators with pharmacist qualifications be eligible to inspect and accept drugs， etc. The related systems were improved， and 17 key points of quality control for the management of IIT drugs were developed. CONCLUSIONS A preliminary IIT drug management system for medical institutions has been established， which helps to improve the institutional X2023076） framework of medical institutions in this field.

ObjectiveTo retrospectively analyze the epidemiological trends of birth defects in perinatal infants in Fengxian District, Shanghai from 2018 to 2022, so as to provide a scientific evidence for the formulation of related prevention and control strategies. MethodsBased on the data from the National Birth Defects Surveillance System, statistical analysis was conducted on the perinatal birth defects from monitored hospitals within the region from 2018 to 2022. ResultsFrom 2018 to 2022, a total of 20 870 perinatal infants delivered in the monitored hospitals in Fengxian District, with 472 cases with birth defects, showing a significant increase in the prevalence of birth defects (PRR=1.49, 95%CI: 1.39‒1.59). The risk of birth defects increased with maternal age, especially for advanced maternal age (PRR=1.58, 95%CI: 1.12‒2.25). Infants born to mothers with gestational diabetes had a higher prevalence of birth defects compared to those without gestational diabetes (PRR=1.99, 95%CI: 1.46‒2.70). Infants with birth defects were more likely to be born prematurely (PRR=2.07, 95%CI:1.56‒2.76). The top three types of birth defects were congenital heart disease (CHD), other anomalies of the external ear, and polydactyly. ConclusionThe prevalence of birth defects in Fengxian District monitored hospitals showed an upward trend from 2018 to 2022. Advanced maternal age and gestational diabetes were identified as risk factors for birth defects. CHD is the leading type of birth defect in Fengxian District over the five-year period. To reduce the prevalence of birth defects, it is crucial to implement comprehensive prevention and treatment measures for CHD.

Currently, researchers have identified several mutated genes associated with hereditary eye diseases; however, effective therapeutic options remain scarce. The emergence of clustered regularly interspaced short palindromic repeats(CRISPR)and its associated proteins(CRISPR-associated proteins, Cas)offers a promising approach for treating these diseases. CRISPR/Cas9 enables precise targeting and modification of specific genetic sequences, allowing for the correction of mutated genes, as well as knockout or replacement of pathogenic genes to achieve therapeutic effects. In ophthalmology, CRISPR/Cas9 has been applied to various hereditary eye disorders, including corneal dystrophy, congenital cataracts, glaucoma, and retinitis pigmentosa. Additionally, significant progress has been made to utilize CRISPR/Cas9 to develop disease models. Therefore, it has great potential for clinical applications. However, challenges such as delivery efficiency and off-target effects remain. This review summarizes the mechanism of CRISPR/Cas9, its applications in genetic eye diseases and disease models, as well as the existing challenges, aiming to provide new insights for treatment.

AIM: To explore the efficacy of 0.05% cyclosporine A combined with olopatadine eye drops in treating allergic conjunctivitis-related dry eye disease.METHODS: A total of 63 patients(63 eyes)with allergic conjunctivitis-related dry eye disease in the People's Hospital of Guangxi Zhuang Autonomous Region from August 2022 to April 2023 were enrolled and randomly divided into control group(n=33)and observation group(n=30). The patients of the control group were administrated with 0.1% olopatadine eye drops and 0.3% sodium hyaluronate eye drops, while the observation group was administrated with 0.1% olopatadine eye drops and 0.05% cyclosporine A eye drops. The ocular surface disease index(OSDI), total ocular symptom score(TOSS), conjunctival congestion score, conjunctival papillae and follicle score, Schirmer I test(SⅠt), tear meniscus height(TMH), meibomian gland secretion ability and property score, meibomian gland loss area score, corneal fluorescein staining(CFS), tear film break-up time(BUT), noninvasive first tear film break-up time(NIBUTf), noninvasive average tear film break-up time(NIBUTav)before and after treatment and the drug safety during the treatment period of both groups of patients were evaluated.RESULTS: After treatment, OSDI, TOSS, conjunctival congestion score, conjunctival papillae and follicle score, SⅠt, TMH, meibomian gland secretion ability score and property score, CFS, BUT, NIBUTf, and NIBUTav of the observation group showed improvements compared with those before treatment(all P<0.017). Among these, OSDI, TOSS, conjunctival congestion score, conjunctival papillae and follicle score, BUT, NIBUTf, and NIBUTav demonstrated significant improvement compared with the control group(all P<0.05). There was no statistically significant difference in meibomian gland loss area score between the two groups before and after treatment(P>0.05). During the treatment period, there were no local or systemic adverse reactions.CONCLUSION: The combined use of 0.05% cyclosporine A and olopatadine eye drops can significantly improve ocular discomfort symptoms of patients with dry eye disease associated with allergic conjunctivitis, such as red eyes, itchy eyes and foreign body sensation, promote tear film stability and have high safety.

BackgroundPrevious studies on subgroups of adolescent non-suicidal self-injury （NSSI） behaviors have predominantly focused on community and school-based samples， with limited research on clinical samples. The precise identification of clinically distinct NSSI subgroups in adolescents is critical for optimizing medical resource allocation. ObjectiveTo explore the subgroups of NSSI in adolescent outpatients， and to provide references for intervening of NSSI behaviors. MethodsFrom May 2021 to April 2022， 192 adolescents who met the NSSI diagnostic criteria as outlined in the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） were recruited from psychiatry or psychology clinics at 6 hospitals in Fujian Province. Participants were assessed using the Adolescent Non-suicidal Self-injury Assessment Questionnaire （ANSAQ）， the Childhood Trauma Questionnaire （CTQ）， the Depression Anxiety Stress Scale-21 item（DASS-21） and the Difficulties in Emotion Regulation Scale （DERS）. Latent profile analysis was conducted using Mplus 8.0. ResultsA total of 192 adolescents with NSSI behaviors completed the study， and the analysis yielded three subgroups of self-injurers： the mild self-injury group （50 cases， 26.04%）， the emotional disorder group （81 cases， 42.19%）， and the severe self-injury group （61 cases， 31.77%）. There were significant differences in the total scores of CTQ， DASS-21 and DERS among the three groups （F=8.058， 51.414， 48.742， P<0.01）. The severe self-injury group exhibited significantly higher scores in CTQ， DASS-21 and DERS when compared to both the mild self-injury group and the emotional disorder group （P<0.05）. Moreover， the emotional disorder group also reported notably higher DASS-21 and DERS scores in comparison to the mild self-injury group （P<0.05）. ConclusionClinical studies on adolescent outpatients engaging in NSSI behaviors reveal three distinct typological profiles， mild self-injury， emotional disorder-related self-injury， and severe self-injury. ［Funded by Fujian Social Science Planning Project （number， FJ2019B173）］

Objective: To explore the current status of hyperopic reserve and its related factors among non-myopia preschool and primary school students aged 5 to 12 years in Guangdong Province, so as to provide a basis for formulating intervention strategies for the pre myopia stage of children. Methods: From October to December 2023, by using stratified cluster random sampling method, a survey on hyperopic reserve among preschool children and primary school students in Guangdong were conducted. And a total of 10 567 children from the senior class of kindergarten to the sixth grade of primary school who completed autorefraction measurements with and without cycloplegia and the questionnaire survey were included in the study. The prevalence characteristics of low hyperopic reserve among non-myopia children were analyzed, and multivariable Logistic regression was used to analyze the related factors. Results: The prevalence rate of low hyperopic reserve among 8 790 non-myopia children was 62.4%. The average spherical equivalent (SE) for children aged 5 to 12 years was 0.88 (0.25, 1.25)D, decreasing from 1.13 ( 0.75 , 1.50)D in senior kindergarten to -1.00 (-2.50, 0.38)D in sixth grade, with the difference was statistically significant ( H=2 475.3, P <0.01). Multivariable Logistic regression analysis, after adjusting for confounders including gender, urban and rural, and grade, revealed that parental myopia was a risk factor for low hyperopic reserve in the preschool stage (one parent with myopia: OR=1.62, 95%CI =1.35-1.93; both parents with myopia: OR=2.05, 95%CI = 1.66 -2.55); in the lower primary school stage, parental myopia (one parent with myopia: OR=1.46, 95%CI =1.27-1.68; both parents with myopia: OR=1.58, 95%CI =1.33-1.89), frequently or always reading or using electronic screens while lying down or on one s stomach ( OR=1.43, 95%CI =1.13-1.81), and never or occasionally maintaining a viewing distance of over 3 meters when watching TV/playing video games ( OR=1.34, 95%CI =1.04-1.72) were risk factors; in the higher primary school stage, failing to take a break every hour during near work ( OR=1.79, 95%CI =1.16-2.75) was a risk factor (all P <0.05). Conclusions The emmetropization of children aged 5-12 years in Guangdong Province is accelerated, and non-myopia children generally exhibit insufficient hyperopic reserve. The contributing factors for insufficient hyperopia reserve in non-myopia children vary across different educational stages, necessitating targeted precision interventions.

Professor ZHANG Boli believed that the core pathogenesis of heart failure with preserved ejection fraction （HFpEF） is weak pulse at yang and wiry pulse at yin. By referring to the theory of “damp-turbidity and phlegm-rheum type of diseases”， he proposed that yin pathogens of damp-turbidity and phlegm-rheum may damage yang qi in each stage of HFpEF， thus aggravating the trend of weak pulse at yang and wiry pulse at yin， which played an important role in the deterioration of HFpEF. Therefore， Professor ZHANG Boli advocated that importance should be attached to the elimination of yin pathogen and the protection of yang qi during the various stages of HFpEF in order to delay the aggravation of weak pulse at yang and wiry pulse at yin； he put forward the idea of staged treatment that “yin pathogen should be dispelled and yang qi should be demonstrated”； and he formulated the treatment strategy of treating the disease as early as possible， eliminating pathogens and protecting yang， interrupting the disease trend， using warm-like medicinals， and activating blood circulation， to enrich the theoretical system of traditional Chinese medicine in the treatment of HFpEF.

Objective To analyze the effect of baseline cytokines in aqueous humor in predicting the improvement of the central macular thickness(CMT)and best corrected visual acuity(BCVA)of patients with macular edema secondary to retinal vein obstruction(RVO-ME)after anti-vascular endothelial growth factor(VEGF)treatment for 3 months.Meth-ods Totally 30 eyes of 30 patients initially diagnosed with RVO-ME in the Affiliated Eye Hospital of Nanjing Medical Uni-versity from October 2021 to January 2023 were enrolled.Aqueous humor was collected by anterior chamber puncture be-fore the anti-VEGF drug injection.The levels of 11 cytokines in aqueous humor,including VEGF,intercellular adhesion molecule(ICAM)-1,interleukins(ILs)and interferon-γ(IFN-γ),were measured by Luminex xMAP technology.The cor-relation between baseline aqueous humor cytokine levels and CMT,BCVA(logMAR)as well as their changes(difference between baseline and anti-VEGF treatment for 3 months)in RVO-ME patients was analyzed;the correlation between CMT and BCVA(logMAR)was analyzed at baseline and 3 months after anti-VEGF treatment.CMT and BCVA responders were defined as patients with 50％or more reduction in CMT and BCVA(logMAR)from baseline to the third month.A Logistic regression model was used to analyze the relationship between baseline aqueous humor cytokines and RVO-ME patients be-coming CMT or BCVA responders after 3 months of anti-VEGF treatment.Results Compared with baseline,the CMT sig-nificantly decreased and BCVA significantly improved in RVO-ME patients after anti-VEGF treatment for 3 months(both P＜0.001).The CMT was positively correlated with BCVA(logMAR)of RVO-ME patients at baseline and after anti-VEGF treatment for 3 months(P=0.026,0.002).At baseline,the levels of VEGF and IL-8 of RVO-ME patients were positively correlated with CMT(P=0.032,0.035);the levels of IL-6 and IL-8 were positively correlated with BCVA(logMAR)(P=0.018,0.002).The baseline IL-8 level in RVO-ME patients was negatively associated with the change in CMT(P=0.024).Logistic regression analysis showed that elevated baseline ICAM-1 level could increase the risk of RVO-ME patients becom-ing BCVA non-responders after 3 months of anti-VEGF treatment(P=0.023).Conclusion Baseline IL-8 and ICAM-1 may be predictors of CMT and BCVA improvement after anti-VEGF treatment of RVO-ME.

Objective:To investigate the efficacy of trimetazidine in the treatment of atrial arrhythmias in patients with ischemic cardiomyopathy and heart failure and analyze the effect of trimetazidine on cardiac function and atrial arrhythmias.Methods:A total of 79 patients with ischemic cardiomyopathy and heart failure who received treatment at the Second Hospital of Jiaxing from December 2018 to June 2020 were included in this study. These patients were randomly divided into an observation group ( n = 41) and a control group ( n = 38). Patients in the control group received conventional drugs, while those in the observation group received trimetazidine sustained-release tablets twice daily, each time taking 35 mg in addition to conventional drugs. The treatment lasted for 24 weeks. Before and after treatment, cardiac function indicators (left ventricular ejection fraction, B-type brain natriuretic peptide, 6-minute walking distance), cardiac color Doppler ultrasound indicators [ratio of early to late peak filling rate (E/A ratio)], left ventricular fractional shortening), electrocardiogram parameters (maximum P-wave duration, minimum P-wave duration, and P-wave dispersion), dynamic electrocardiogram parameters [number of single atrial premature beats, total number and duration of paroxysmal atrial tachycardia episodes, total number and duration of paroxysmal atrial flutter/fibrillation attacks, standard deviation of RR intervals, root mean square of successive differences between normal heartbeats, proportion of successive RR intervals that differ by more than 50 ms divided by the total number of NN intervals (PNN50), standard deviation of average NN intervals, high frequency and low frequency], as well as changes in high sensitivity C-reactive protein were analyzed in each group. Results:After treatment, left ventricular ejection fraction, B-type brain natriuretic peptide, 6-minute walking distance, maximum P-wave duration, P-wave dispersion, total number of atrial flutter/atrial fibrillation attacks, and duration of atrial flutter/atrial fibrillation in the observation group were (51.05 ± 7.68)%, (1 615.59 ± 1 129.78) ng/L, (350.02 ± 62.99) m, (99.73 ± 11.60) ms, (22.44 ± 12.03) ms, (0.22 ± 0.61), and (4.59 ± 12.30) minutes, respectively, which were significantly superior to (46.82 ± 7.34)%, (2 267.47 ± 1 539.03) ng/L, (294.16 ± 58.20) m, (111.71 ± 10.00) ms, (36.77 ± 15.07) ms, (0.76 ± 1.13), (15.66 ± 22.30) minutes in the control group, t = -2.95, 2.16, -4.08, 4.89, 4.68, 2.69, 2.76, all P < 0.01). Conclusion:Trimetazidine can effectively reduce atrial arrhythmias and improve the prognosis of patients with ischemic cardiomyopathy and heart failure, which warrants clinical promotion.