AIM: To analyze the clinical features and multimodal imaging features of peripapillary hyper-reflective ovoid mass-like structure(PHOMS).METHODS: Retrospective observation study. Totally 35 patients(56 eyes)with PHOMS that diagnosed in the Affiliated Eye Hospital of Nanjing Medical University from January 2020 to March 2024 were included in the study. All patients underwent fundus photography, fundus fluorescein angiography, fundus autofluorescence, optical coherence tomography, and B-ultrasound.RESULTS:PHOMS occurred across diverse age groups, with an insidious onset often detected incidentally during routine ophthalmic examinations. More patients came to hospital for refractive errors due to blurred vision The boundary of the optic disc is blurred on fundus photography, and the nasal eminence is more significant, showing a “C” shaped halo. No obvious abnormal fluorescence was observed on fundus autofluorescence and fundus fluorescein angiography during different periods. An elevated appearance in vary degrees with more prominent in the nasal parts was showed on different OCT scans. Vertical scanning on the nasal side of the optic disc showed the best PHOMS structure, which could be seen under the retinal nerve fiber layer and on the Bruch membrane, with sharply marginated hyper-reflective ovoid mass-like structures, and no shielding effect on the choroid. The higher the elevation, the larger the volume. Ocular B-mode ultrasound showed a pre-optic disc bulge on the posterior wall of the eyeball, and there was no strong signal echo in it.CONCLUSION:PHOMS can be found frequently in myopic patients and often asymptomatic. Transient vision loss and floaters may occur in symptomatic cases. The most typical OCT feature is a nasally located hyper-reflective ovoid structure with distinct margins.

Objective: To evaluate the incremental vaccine effectiveness (VE) of two dose of the mumps containing vaccine (MuCV) in chidren, so as to provide a basis for optimizing mumps immunization strategies. Methods: A 1∶2 frequency matched case-control study was conducted by using reported mumps cases in childcare centers or schools from Lu an, Hefei, Ma anshan and Huainan cities of Anhui Province from September 1, 2023 to June 30, 2024, as a case group(383 cases). And healthy children in the same classroom were selected as a control group(766 cases). The MuCV immunization histories of participants were collected to estimate the incremental VE of the second dose of MuCV against mumps. Group comparisons were performed using the Chi square test or t-test. For matched case-control pairs, the Cox regression model was employed to calculate the odds ratio (OR) with 95% confidence interval (CI) for two dose MuCV vaccination and to estimate the incremental vaccine effectiveness (VE). Results: There were no statistically significant differences between the case and control groups regarding gender, age, dosage of MuCV vaccination and the time interval since the last dose vaccination( χ 2/t=0.05, 0.20, 0.94, -0.02, P >0.05). The proportions of the case and control groups vaccinated with two doses of MuCV were 26.63% and 29.37%, respectively, and the overall incremental VE of the second dose of MuCV was 40.73% (95% CI=3.03%-63.77%, P <0.05). Subgroup analyses revealed that the incremental VE for children with a period of ≥1 year between the two doses of MuCV was 54.13% (95% CI=1.90%-78.56%, P <0.05), while for children with a period of <1 year, it was 30.63% (95% CI=-28.59%-62.58%, P >0.05). The incremental VE of the second dose of MuCV was 30.36% (95% CI=-25.95%-61.50%, P >0.05) in kindergarten children and 66.73% (95% CI=14.92%-86.99%, P <0.05) in elementary and secondary school students. The incremental VE was 28.78% (95% CI=-27.46%-60.21%, P >0.05) within five years of the last dose of MuCV vaccination and 66.07% (95% CI=-41.56%-91.87%, P >0.05) for vaccinations administered beyond five years. Conclusions The second dose of MuCV may offer additional protection for children; however, extending the interval between two dose of MuCV (<1 year) has shown limited incremental protective effects. Therefore, it is crucial to consider optimizing current immunization strategies for mumps.

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.

ObjectiveThe detection of RNA single nucleotide polymorphism (SNP) is of great importance due to their association with protein expression related to various diseases and drug responses. At present, splintR ligase-assisted methods are important approaches for RNA direct detection, but its specificity will be limited when the fidelity of ligases is not ideal. The aim of this study was to create a method to improve the specificity of splintR ligase for RNA detection. MethodsIn this study, a dual-competitive-padlock-probe (DCPLP) assay without the need for additional enzymes or reactions is proposed to improve specificity of splintR ligase ligation. To verify the method, we employed dual competitive padlock probe-mediated rolling circle amplification (DCPLP-RCA) to genotype the CYP2C9 gene. ResultsThe specificity was well improved through the competition and strand displacement of dual padlock probe, with an 83.26% reduction in nonspecific signal. By detecting synthetic RNA samples, the method demonstrated a dynamic detection range of 10 pmol/L-1 nmol/L. Furthermore, clinical samples were applied to the method to evaluate its performance, and the genotyping results were consistent with those obtained using the qPCR method. ConclusionThis study has successfully established a highly specific direct RNA SNP detection method, and provided a novel avenue for accurate identification of various types of RNAs.

Background::Ainuovirine (ANV) is a new generation of non-nucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus (HIV) type 1 infection. This study aimed to evaluate the population pharmacokinetic (PopPK) profile and exposure-response relationship of ANV among people living with HIV.Methods::Plasma concentration-time data from phase 1 and phase 3 clinical trials of ANV were pooled for developing the PopPK model. Exposure estimates obtained from the final model were used in exposure-response analysis for virologic responses and safety responses.Results::ANV exhibited a nonlinear pharmacokinetic profile, which was best described by a two-compartment model with first-order elimination. There were no significant covariates correlated to the pharmacokinetic parameters of ANV. The PopPK parameter estimate (relative standard error [%]) for clearance adjusted for bioavailability (CL/F) was 6.46 (15.00) L/h, and the clearance of ANV increased after multiple doses. The exposure-response model revealed no significant correlation between the virologic response (HIV-RNA <50 copies/mL) at 48 weeks and the exposure, but the incidence of adverse events increased with the increasing exposure ( P value of steady-state trough concentration and area under the steady-state curve were 0.0177 and 0.0141, respectively). Conclusions::Our PopPK model supported ANV 150 mg once daily as the recommended dose for people living with HIV, requiring no dose adjustment for the studied factors. Optimization of ANV dose may be warranted in clinical practice due to an increasing trend in adverse reactions with increasing exposure.Trial registration::Chinese Clinical Trial Registry https://www.chictr.org.cn (Nos. ChiCTR1800018022 and ChiCTR1800019041).

Objective To determine the effective dose of dexmedetomidine administered intranasally combined with oral midazolam sedation before pediatric magnetic resonance image(MRI).Methods This is a prospective modified sequential study.Children scheduled for MRI at the Children's Hospital of Zhejiang University School of Medicine from February to March 2023,aged 1 month to 6 years old,with a weight of 6.0-23.5 kg,were enrolled in this study.All children received 0.5 mg/kg oral midazolam,followed by intranasal dexmedetomidine.The initial dose of dexmedetomidine was 0.5 μg/kg,and the intranasal dose of dexmedetomidine was determined using the modified Dixon's up-and-down method with increments or decrements of 0.1 μg/kg.Probit analysis was used for calculating the half effective dose(ED50),95%effective dose(ED95)and the corresponding 95%confidence interval(CI)of intranasal dexmedetomidine combined with oral midazolam for pediatric sedation during MRI.The sedation onset time,wake-up time,vital signs and adverse reactions were recorded.Results Among all the children,the sedation onset time of successful sedation children was(31.21±7.47)min,and the wake-up time was(81.21±26.04)min.The ED50 for effective sedation with intranasal dexmedetomidine combined with oral medication at a dose of 0.5 mg/kg was calculated to be 0.392 μg/kg,with a 95%CI of 0.302-0.461 μg/kg;the ED95 was 0.549 μg/kg,with a 95%CI of 0.473-0.996 μg/kg.There was a statistically significant difference(P<0.05)in heart rate and diastolic blood pressure after sedation compared to the baseline before medication.Two cases of restlessness during the awakening period were observed,but no other adverse reactions occurred.Conclusions The sedation regimen of intranasal dexmedetomidine combined with oral midazolam is non-invasive,easy to implement,safe,and effective.It can be widely used in pediatric MRI.

Objective: To investigate the resistance to rifampicin and isoniazid and the changing trends among patients with pulmonary tuberculosis in Luohu District, Shenzhen City, Guangdong Province from 2012 to 2022, so as to provide insights into improving drug-resistant pulmonary tuberculosis control and prevention strategies. Methods: Basic information, treatment classification and drug resistance data of patients with pulmonary tuberculosis and positive pathogenic detection in Luohu District from 2012 to 2022 were collected through the Tuberculosis Surveillance System of Chinese Disease Prevention and Control Information System, and resistance rates of rifampicin and isoniazid and the changing trends were analyzed. Results: A total of 2 126 patients with pulmonary tuberculosis were collected and had a median age of 34 (interquartile range, 25) years, including 1 334 males (62.75%) and 792 females (37.25%). There were 302 patients with drug-resistance in Luohu District from 2012 to 2022, with a resistance rate of 14.21%. Among them, 60 patients were monoresistant to rifampicin (2.82%), 113 patients were monoresistant to isoniazid (5.32%), and 129 patients were multidrug resistant (6.07%). The rate of rifampicin monoresistance showed a downward trend from 2012 to 2022, while the rate of multidrug resistance showed an upward trend (both P<0.05). There was no significant tendency in the rate of isoniazid monoresistance (P>0.05). The rate of multidrug resistance among patients without Shenzhen residence was higher than that among patients with Shenzhen residence; the rates of rifampicin resistance and multidrug resistance among retreated patients were higher than those among treatment-naïve patients (all P<0.05). Conclusions The rate of rifampicin monoresistance appeared a downward trend and the rate of multidrug resistance appeared an upward trend among patients with pulmonary tuberculosis in Luohu District from 2012 to 2022. Attention should be given to non-Shenzhen residence and retreated patients.

ObjectiveTemporal heterogeneity in lung cancer presents as fluctuations in the biological characteristics, genomic mutations, proliferation rates, and chemotherapeutic responses of tumor cells over time, posing a significant barrier to effective treatment. The complexity of this temporal variance, coupled with the spatial diversity of lung cancer, presents formidable challenges for research. This article will pave the way for new avenues in lung cancer research, aiding in a deeper understanding of the temporal heterogeneity of lung cancer, thereby enhancing the cure rate for lung cancer. MethodsRaman spectroscopy emerges as a powerful tool for real-time surveillance of biomolecular composition changes in lung cancer at the cellular scale, thus shedding light on the disease’s temporal heterogeneity. In our investigation, we harnessed Raman spectroscopic microscopy alongside multivariate statistical analysis to scrutinize the biomolecular alterations in human lung epithelial cells across various timeframes after benzo(a)pyrene exposure. ResultsOur findings indicated a temporal reduction in nucleic acids, lipids, proteins, and carotenoids, coinciding with a rise in glucose concentration. These patterns suggest that benzo(a)pyrene induces structural damage to the genetic material, accelerates lipid peroxidation, disrupts protein metabolism, curtails carotenoid production, and alters glucose metabolic pathways. Employing Raman spectroscopy enabled us to monitor the biomolecular dynamics within lung cancer cells in a real-time, non-invasive, and non-destructive manner, facilitating the elucidation of pivotal molecular features. ConclusionThis research enhances the comprehension of lung cancer progression and supports the development of personalized therapeutic approaches, which may improve the clinical outcomes for patients.

Objective To investigate the changes of serum metabolites in patients with occupational chronic lead poisoning using non-targeted metabolomics, and to screen differential metabolic pathways. Methods A total of 14 patients with occupational chronic lead poisoning were selected as the poisoning group, and 14 healthy people without occupational hazard exposure history were selected as the control group using the judgment sampling method. Serum of the individuals from the two groups was collected. Non-targeted metabolomics technology based on ultra high performance liquid chromatography-tandem mass spectrometry was used to detect serum metabolite levels in the two groups. Differential metabolites (DMs) were screened by the principal component analysis, partial least squares discriminant analysis and orthogonal partial least squares discriminant analysis, and related metabolic pathways were explored. Results The blood lead level in the poisoning group was higher than that in the control group (median: 359.59 vs 5.04 μg/L, P<0.01). There were significant differences in serum metabolites between the poisoning group and control group. After the combination of results from the positive and negative ion patterns, a total of 89 DMs were screened in serum of patients in the poisoning group, including 50 upregulated and 39 downregulated metabolites compared with the control group. The serum DMs of poisoning group were mainly enriched in arginine biosynthesis, ABC transporter, purine metabolism, choline metabolism in malignant tumor, glycerophospholipid metabolism and ether lipid metabolism compared with the control group (all P<0.05). Conclusion Abnormal changes of serum metabolic profile occurred in patients with occupational chronic lead poisoning. The metabolic pathways such as arginine biosynthesis, ABC transporter, purine metabolism, choline metabolism, glycerophospholipid metabolism and ether lipid metabolism may be involved in the occurrence and development of lead poisoning.

Aim To explore the effect and mechanism of the artesunate(ART)on hepatocellular carcinoma(HCC).Methods The cell lines MHCC-97H and HCC-LM3 were used to be detected.MTT and clone formation were used to determine the cell proliferation;Wound healing was used to detect the cell migration;Transwell was used to test the cell invasion.Flow-cy-tometry was used to detect cell apoptosis and cell cy-cle.RNA-seq and qRT-PCR was used to detect the genes expression.Results The proliferation,migra-tion and invasion of treated cells were obviously inhibi-ted(P＜0.01).Moreover,the apoptosis rate in-creased significantly,so did the proportion of G2/M cells.Transcriptomic analysis identified GADD45A as a potential target of ART through RNA-sequencing da-ta,and suggested that ART might induce apoptosis and cell cycle arrest through regulating the expression of GADD45A.In addition,the results of mechanism studies and signaling analysis suggested that GADD45A had interaction with its upstream gene NACC1(nucle-us accumbens associated 1).Moreover,after ART treatment,the expressions of GADD45A and NACC1 were changed significantly.Conclusion ART may be a potential drug to resist HCC by affecting the expres-sion of GADD45A and its upstream gene NACC1,which provides a new drug,a new direction and a new method for the clinical treatment of HCC.