AIM: To investigate the differences in morphological structure and retinal blood perfusion between the affected eye and the contralateral healthy eye using optical coherence tomography angiography(OCTA)in patients with idiopathic macular epiretinal membrane(IMEM)before and after surgery, and to evaluate the association of these parameters with functional and anatomical outcomes to inform prognostic assessment. METHODS:A prospective study was conducted at Zhejiang Provincial People's Hospital between January 2023 and December 2024. Consecutive patients diagnosed with unilateral IMEM were enrolled; the fellow eye served as an internal control. All participants underwent standardized ophthalmic evaluations, including optical coherence tomography(OCT), OCTA, and color fundus photography. Key quantitative parameters assessed included best-corrected visual acuity(BCVA), central macular thickness(CMT), foveal avascular zone(FAZ)area, vessel density in the inner capillary plexus(ICP), superficial capillary plexus(SCP), deep capillary plexus(DCP), and choroidal capillary perfusion area(CCPA). Measurements were obtained preoperatively and at 1 and 3 mo postoperatively. Correlation analyses were performed between the above parameters and postoperative BCVA and CMT.RESULTS: This study enrolled 30 patients(60 eyes)diagnosed with IMEM, comprising 14 males and 16 females, with a mean age of 65.4±10.8 y.At baseline, IMEM-affected eyes demonstrated significantly reduced BCVA, DCP density, and FAZ area, alongside significantly increased CMT and CCPA, compared with contralateral controls. Following vitrectomy with membrane peeling, CMT decreased significantly at both 1 and 3 mo(both P<0.05)postoperatively; DCP density and BCVA showed significant improvement(both P<0.05). No significant change in FAZ area was observed postoperatively(P>0.05). At 3 mo postoperatively, BCVA of the affected eye was negatively correlated with CMT(r=-0.549, P=0.022). At 1 mo postoperatively, CMT was negatively correlated with preoperative DCP and FAZ, positively correlated with preoperative CMT, and positively correlated with ICP and SCP at 1 mo postoperatively, and negatively correlated with FAZ at 1 mo postoperatively(all P<0.05). Furthermore, CMT at 3 mo postoperatively was negatively correlated with preoperative DCP(r=-0.498,P=0.042).CONCLUSION:In patients with IMEM, the affected eyes exhibit significantly reduced DCP density and FAZ area, alongside increased CMT and CCPA. Following vitrectomy with membrane peeling, CMT decreased progressively, DCP density demonstrated partial restoration, and vision improved gradually. Preoperatively, smaller CMT larger DCP, and FAZ were associated with more favorable surgical outcomes; postoperatively, smaller ICP and SCP densities—combined with a larger FAZ—also correlated with better functional recovery.

Although cisplatin is a widely used chemotherapeutic agent, it is severely toxic and causes irreversible hearing loss, restricting its application in clinical settings. This study aimed to determine the molecular mechanism underlying cisplatin-induced ototoxicity. Here, we established in vitro and in vivo ototoxicity models of cisplatin-induced hair cell loss, and our results showed that reducing STING levels decreased inflammatory factor expression and hair cell death. In addition, we found that cisplatin-induced mitochondrial dysfunction was accompanied by cytosolic DNA, which may act as a critical linker between the cyclic GMP-AMP synthesis-stimulator of interferon genes (cGAS-STING) pathway and the pathogenesis of cisplatin-induced hearing loss. H-151, a specific inhibitor of STING, reduced hair cell damage and ameliorated the hearing loss caused by cisplatin in vivo. This study underscores the role of cGAS-STING in cisplatin ototoxicity and presents H-151 as a promising therapeutic for hearing loss.
Cisplatin/toxicity* ; Animals ; Nucleotidyltransferases/antagonists & inhibitors* ; Membrane Proteins/antagonists & inhibitors* ; Signal Transduction/drug effects* ; Mice ; Hair Cells, Auditory, Inner/pathology* ; Antineoplastic Agents/toxicity* ; Mice, Inbred C57BL ; Hearing Loss/metabolism* ; Male ; Ototoxicity/metabolism*

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder worldwide, causing dementia and affecting millions of individuals. One prominent characteristic in the brains of AD patients is glucose hypometabolism. In the context of galactose metabolism, intracellular glucose levels are heightened. Galactose mutarotase (GALM) plays a crucial role in maintaining normal galactose metabolism by catalyzing the conversion of β-D-galactose into α-D-galactose (α-D-G). The latter is then converted into glucose-6-phosphate, improving glucose metabolism levels. However, the involvement of GALM in AD progression is still unclear. In the present study, we found that the expression of GALM was significantly increased in AD patients and model mice. Genetic knockdown of GALM using adeno-associated virus did not change the expression of amyloid precursor protein (APP) and APP-cleaving enzymes including a disintegrin and metalloprotease 10 (ADAM10), β-site APP-cleaving enzyme 1 (BACE1), and presenilin-1 (PS1). Interestingly, genetic overexpression of GALM reduced APP and Aβ deposition by increasing the maturation of ADAM10, although it did not alter the expression of BACE1 and PS1. Further electrophysiological and behavioral experiments showed that GALM overexpression significantly ameliorated the deficits in hippocampal CA1 long-term potentiation (LTP) and spatial learning and memory in AD model mice. Importantly, direct α-D-G (20 mg/kg, i.p.) also inhibited Aβ deposition by increasing the maturation of ADAM10, thereby improving hippocampal CA1 LTP and spatial learning and memory in AD model mice. Taken together, our results indicate that GALM shifts APP processing towards α-cleavage, preventing Aβ generation by increasing the level of mature ADAM10. These findings indicate that GALM may be a potential therapeutic target for AD, and α-D-G has the potential to be used as a dietary supplement for the prevention and treatment of AD.
Animals ; ADAM10 Protein/metabolism* ; Alzheimer Disease/pathology* ; Amyloid Precursor Protein Secretases/metabolism* ; Disease Models, Animal ; Humans ; Mice ; Amyloid beta-Peptides/metabolism* ; Male ; Mice, Transgenic ; Membrane Proteins/metabolism* ; Cognitive Dysfunction/pathology* ; Mice, Inbred C57BL ; Amyloid beta-Protein Precursor/metabolism* ; Female ; Hippocampus/metabolism* ; Long-Term Potentiation/physiology*

Objective:To determine whether spinal cord injury (SCI) triggers secondary neuroinflammation and neuronal injury in remote brain regions by impairing the drainage function of the meningeal lymphatic vessels (MLVs).Methods:Fifty-two female C57BL/6 mice were assigned with the random number table into four groups ( n=13 per group): sham group, SCI group, adeno-associated virus negative control group (negative control group), and adeno-associated virus overexpressing VEGF-C group (VEGF-C group). The sham group underwent laminectomy without spinal cord injury. In the SCI group, negative control group and VEGF-C group, T 9 contusion was made to establish the SCI models using a modified Allen′s impactor. At 4 weeks before SCI modeling, the negative control group and VEGF-C group were injected via the cisterna magna with 3 μl adeno-associated virus for negative control or adeno-associated virus for VEGF-C overexpression. At 56 days after injury, Alexa Fluor? 647 ovalbumin conjugate (OVA-647) was injected via the cisterna magna as a tracer. Two hours later, the proportion of OVA-647 in the deep cervical lymph nodes (dCLN) was detected. Immunofluorescence was performed to assess the proportion of MLVs marker lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) and expression levels of microglial marker ionized calcium-binding adaptor molecule 1 (Iba1) in the cerebral cortex, hippocampus, midbrain, and thalamus across the experimental groups. ELISA was employed to quantify the levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) and Nissl staining was used to assess neuronal counts in these regions. Results:At 56 days after injury, the OVA-647 proportion in the dCLN was higher in the sham group than that in the SCI group and negative control group ( P<0.01), whereas the SCI group and negative control group showed a lower OVA-647 proportion in the dCLN than the VEGF-C group ( P<0.05). At 56 days after injury, the dural LYVE-1 proportion was higher in the sham group than that in the SCI group and negative control group ( P<0.01), whereas it was lower in the SCI group and negative control group than that in the VEGF-C group ( P<0.05). At 56 days after injury, the count of Iba1-positive microglia across all the above-mentioned regions was increased in the SCI group and negative control group ( P<0.01), compared with that in the sham group, whereas it was reduced in these regions in the VEGF-C group, compared with that in the SCI group and negative control group ( P<0.01). At 56 days after injury, TNF-α and IL-1β levels in these regions were both elevated in the SCI group and negative control group when compared with those in the sham group ( P<0.05), whereas they were reduced in the VEGF-C group, compared with those in the SCI group and negative control group ( P<0.05). At 56 days after injury, neuronal survival in the regions was decreased in the SCI group and negative control group, compared with that in the sham group ( P<0.05), whereas it was increased in the VEGF-C group, compared with that in the SCI group and negative control group ( P<0.05). Conclusion:SCI can induce secondary neuroinflammation and neuronal damage in remote brain regions by impairing the drainage function of MLVs.

Objective:To identify the bacteria isolated from sepsis patients in a tertiary hospital in Shanghai and analyze their antimicrobial resistance features.Methods:This study included 439 patients with clinically diagnosed sepsis who underwent microbiological culture in a tertiary hospital in Shanghai from July 2021 to October 2024. Results of microbiological culture and antimicrobial susceptibility testing were retrospectively collected and analyzed. Differences between groups were analyzed using Chi-square test and Fisher′s exact test. Results:The positive rate of microbiological culture was 49.0% (215/439). The positive rate of blood culture was 24.1% (93/386) and 100 strains were isolated from the samples, including 57 Gram-negative bacteria (57.0%). The predominant isolates in blood samples were Escherichia coli, Klebsiella pneumoniae, and coagulase-negative staphylococci. The positive rate of bacterial culture from bronchoalveolar lavage fluid samples was 84.1% (37/44), with Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa being the predominant strains. The positive rate of bacterial culture from urine samples was 35.6% (127/357), with Escherichia coli, Klebsiella pneumoniae, and Enterococcus faecium being the most common. Escherichia coli, Klebsiella pneumoniae, Enterococcus faecium, coagulase-negative staphylococci, Pseudomonas aeruginosa, and Acinetobacter baumannii exhibited high resistance rates to fluoroquinolones [46.8% (29/62)-97.0% (32/33)]. The resistance rates of Acinetobacter baumannii to most commonly used antibiotics were >80.0%. The resistance rates of Escherichia coli and Klebsiella pneumoniae to the third-generation cephalosporins ranged from 41.8% (28/67) to 66.0% (31/47). Carbapenem resistance was observed in 38.1% (24/63)-40.3% (25/62) of Klebsiella pneumoniae isolates, and most of the isolates from bronchoalveolar lavage fluid samples showed a higher resistance rate than those from blood or urine samples ( P<0.05). Conclusions:The positive rate of bacterial culture is nearly 50% in this study, with Gram-negative bacteria being the most common. Six major pathogenic bacteria exhibit high resistance rates to fluoroquinolones. Klebsiella pneumoniae isolates have high resistance rates to the third-generation cephalosporins and carbapenems, with significant differences in the resistance rate between isolates from different samples, and it should be cautious to choose the third-generation cephalosporins and carbapenems in clinical practice.

Objective:To investigate the efficacy of naloxone in improving health-related quality of life in patients with chronic arsenic exposure-related pruritus, and to explore the modification effect of gene polymorphisms associated with arsenic metabolism and endorphin receptors.Methods:A randomized, double-blind, placebo-controlled trial was conducted between January and March 2019 in Changde City, Hunan Province, China. Eligible patients with moderate to severe chronic pruritus under arsenic exposure were recruited, and randomly assigned to the naloxone group and the control group to receive sublingual naloxone and placebo (0.4 mg/d) respectively for 7 consecutive days. Outcomes were assessed before treatment and on day 7 after treatment, including the primary outcome (the dermatology life quality index [DLQI]) and secondary outcomes (depression symptoms, anxiety symptoms, and quality of sleep). Genotyping of the arsenic (+3 oxidation state) methyltransferase and 3 opioid receptor genes was performed using ligase detection reaction. Data analysis was performed using t test for normally distributed continuous variables, non-parametric tests for skewed continuous variables, and chi-square test for categorical data. Linear regression analysis was carried out to evaluate the effect of naloxone on outcome measures, while the interactive effect of demographic factors, genotypes and treatment methods on changes in DLQI were assessed by the generalized linear model. Results:A total of 126 patients with chronic arsenic exposure-related pruritus were enrolled, including 73 males and 53 females. They were randomly divided into the control group (64 cases) and the naloxone group (62 cases), with the ages being 60.0 ± 9.1 years and 58.4 ± 8.6 years, respectively. There were no significant differences between the two groups in terms of age, gender, income, education levels, or hair arsenic concentrations (all P > 0.05). After treatment, the decrease in DLQI scores was significantly higher in the naloxone group than in the control group (-8.79 ± 6.84 vs. -5.19 ± 8.10; P = 0.008). However, there were no significant changes in depression symptoms, anxiety symptoms, or quality of sleep between the naloxone group and control group (all P > 0.05). Linear regression analysis showed that naloxone significantly affected DLQI with a crude regression coefficient of -3.60 (95% CI: -6.25, -0.96; P = 0.008). Stratification analysis revealed that patients with the κ-opioid receptor gene rs1051660 (wild-type, CC) responded better to the treatment than those with the mutated genotype (CA), and there was a significant interaction between the rs1051660 genotype and therapeutic drugs in relation to DLQI changes ( P = 0.014) . Conclusion:Naloxone can effectively improve health-related quality of life in patients with chronic arsenic exposure-related pruritus, and its efficacy is modified by the gene polymorphism of the κ-opioid receptors.

Objective:To explore the position and length of anchor placement during the repair of anterior talofibular ligament (ATFL) in adolescents with unclosed epiphyseal plates by measuring the relevant data in three-dimensional CT.Methods:A total of 100 three-dimensional CT images of adolescent patients with unclosed epiphyseal plates were collected from the database of the Radiology Center of Renhe Hospital Affiliated to China Three Gorges University from January 1, 2017 to January 1, 2024. There were 69 males and 31 females, aged 12.38±0.90 years (range, 11-14 years), 47 on the left side and 53 on the right side, with a height of 155.72±5.84 cm (range, 145-175 cm), a weight of 48.02±5.93 kg (range, 40-72 kg), and a body mass index (BMI) of 19.77±1.61 kg/m 2 (range, 17.69-24.91 kg/m 2). The built-in measurement tool of the picture archiving and communication system (PACS) was used to measure the angle (α) between the direction of the nail placement and the longitudinal axis of the fibula, the distance between the nail placement point and the posterior edge of the fibula ( d), and the height from the nail placement point to the level of the fibula tip ( h) to evaluate the position and length of the anchor placement. Results:In adolescent patients, α was 47.50°±3.28° (range, 40.00°-56.00°), d was 17.12±1.80 mm (range, 11.70-21.90 mm), and h was 5.21±1.17 mm (range, 3.40-7.90 mm). The α, d and h of male patients were 47.48°±3.13° (range, 42.00°-56.00°), 17.49±1.54 mm (range, 14.45-21.90 mm) and 5.25±1.07 mm (range, 3.70-7.90 mm), respectively. Those of female patients were 47.55°±3.66° (range, 40.00°-53.00°), 16.30±2.07 mm (range, 11.65-20.30 mm) and 5.07±1.56 mm (range, 3.40-7.00 mm), respectively. There was a significant difference in d between male and female patients ( t=3.193, P=0.002), but there was no significant difference in α and h ( t=0.098, P=0.922; t=0.296, P=0.770). Conclusions:The safe range of anchor placement during ATFL anatomical repair in adolescents with unclosed epiphyseal plates is about 3.40-7.90 mm above the tip of fibula and 56°-90° with the longitudinal axis of fibula. Male patients with unclosed epiphyseal plates should choose anchors with a length of 14 mm and shorter, while females should choose anchors with a length of 10.8 mm.

Objective:To investigate the clinical characteristics, prevalent serum groups, and drug sensitivity test results of epidemic cerebrospinal meningitis in children in Shanghai area.Methods:The study was a retrospective case-control study. The children hospitalized for epidemic cerebrospinal meningitis in Children′s Hospital of Fudan University from January 2003 to December 2023 were enrolled. Clinical data were collected, including demographic characteristics, clinical manifestations, pathogen detection results, strain typing, and drug sensitivity test results.Results:A total of 77 children with confirmed epidemic cerebrospinal meningitis were hospitalized, including 50 males (64.94%) and 27 females (35.06%). The age was 24(8, 60) months, with 16 cases (20.78%) aged 0 to five months, nine cases (11.69%) aged six to 11 months, 21 cases (27.27%) aged 12 to 35 months, 16 cases (20.78%) aged three to five years, 13 cases (16.89%) aged six to 11 years, and two cases (2.60%) aged 12 years. The highest number of cases was in spring, with 36 cases (46.75%), followed by winter with 25 cases (32.47%). Thirty-three cases (42.86%) had vaccinated with meningococcal vaccine. The clinical symptoms included fever in all 77 cases (100.00%), skin petechiae and ecchymosis in 58 cases (75.32%), vomiting in 56 cases (72.73%), respiratory symptoms in 12 cases (15.58%), convulsions in 17 cases (22.08%), conscious disturbance in 24 cases (31.17%), shock in 38 cases (49.35%), circulatory failure in 13 cases (16.88%), and respiratory failure in seven cases (9.09%). Among the 77 children, fifty-seven cases (74.03%) were common type and 20 cases (25.97%) were fulminant type, with seven deaths (9.09%). Neisseria meningitidis (Nm) was detected in 55 cases (71.43%), with the positive rates of skin petechiae smear and cerebrospinal fluid smear of 23.26%(10/43) and 19.44%(14/72), respectively. The positive rates of cerebrospinal fluid culture and blood culture were 36.51%(23/63) and 31.51% (23/73), respectively. The positive rate of polymerase chain reaction detection was 79.17%(38/48). The serogroups were determined in the 38 Nm strains, including 18 cases (47.37%) of group B, 14 cases (36.84%) of group C, five cases (13.16%) of group A, and one case (2.63%) of group Y. Among the 29 Nm strains tested for antimicrobial susceptibility, one strain (3.45%) was resistant to penicillin, two strains (6.90%) were resistant to cefotaxime, 21 strains (72.41%) were resistant to ciprofloxacin, and 25 strains (86.21%) were resistant to sulfamethoxazole/trimethoprim. All strains were sensitive to ceftriaxone, azithromycin, meropenem, rifampicin, chloramphenicol, and minocycline. Conclusions:Epidemic cerebrospinal meningitis presents a low prevalence trend in children in Shanghai area. Infants and toddlers remain the major susceptible individuals. Nm has reduced sensitivity to penicillin, but remains sensitive to ceftriaxone. Ceftriaxone is recommended as the first-line choice for antibiotic therapy. The prevalent serogroups are Group B, Group C, Group A and Group Y in sequence. Immunization plan adjustment should be suggested. Vaccination covering the current epidemic serum population as early as possible should be recommended.

A 37-year-old male patient was admitted to a certain tertiary hospital in Shanghai on May 10, 2024 due to "sudden cough accompanied by chest pain for 2 days". Smear examination of pleural effusion revealed Gram-positive cocci. A positive result was reported after 3.8 days of anaerobic culture, and the isolate was identified as Parvimonas micra by mass spectrometry. Based on the patient′s medical history, imaging and etiological examination results of pleural effusion, the patient was diagnosed with encapsulated empyema caused by Parvimonas micra infection. After anti-infection treatment with imipenem and linezolid and pleural effusion drainage, the patient improved and was discharged. Whole-genome sequencing analysis revealed that this bacterium carried the drug resistance gene tetM and phylogenetic tree analysis showed that it was closely related to a strain from an apical abscess in South Korea.