Early-life exposure to ambient air pollutants and kidney function in adolescents: a cohort study based on the 'Children of 1997' Hong Kong birth cohort.

OBJECTIVES: Air pollution is increasingly linked to impaired kidney function in adults. However, little is known about how early-life exposure to air pollutants affects kidney function in adolescents. STUDY DESIGN: Cohort study. METHODS: We leveraged data from the 'Children of 1997' Hong Kong population-representative birth cohort (N = 8327). Residential exposure to average ambient levels of four air pollutants, including inhalable particle (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), and nitrogen monoxide (NO), during in utero, infancy, and childhood periods was estimated using the inverse distance weighting. Kidney function was assessed using estimated glomerular filtration rate (eGFR) calculated from age-adjusted equations for adolescents. Generalized linear regression was used to examine the association of air pollutant exposure in each period with kidney function at 17.6 years. Two-pollutant models tested the robustness of the association. RESULTS: Of the 3350 participants included, 51.4% were boys. Exposure to PM10 was associated with poorer kidney function. Each interquartile range increment in PM10 was inversely associated with eGFR (ß: -2.933, 95% confidence interval -4.677 to -1.189) in utero, -2.362 (-3.992 to -0.732) infancy, -2.708 (-4.370 to -1.047) childhood, and -2.828 (-4.409 to -1.247) overall. Exposure to PM10 and SO2in utero had a stronger inverse association with kidney function in males. The associations were robust to PM10 exposure in two-pollutant models. CONCLUSIONS: Our findings suggest that early-life exposure to ambient PM10 and SO2 is associated with reduced kidney function in adolescents, especially exposure in utero.

Independent and combined effects of smoking, drinking and depression on periodontal disease.

BACKGROUND: Periodontitis is a complex chronic inflammatory disease that is particularly associated with health-related conditions such as smoking, excessive drinking and depression. This research aimed to investigate the interaction between these lifestyles factors on periodontitis risk. METHODS: This study included participants who participated in the National Health and Nutrition Examination Survey in the United States between 2009 and 2014. They had completed oral health-periodontal examination, Smoking-Cigarette Use Questionnaire, Alcohol Use Questionnaire, and Patient Health Questionnaire. Periodontal clinical attachment loss (CAL) of 3 mm or more and Patient Health Questionnaire-9 (PHQ-9) of 10 scores or more were used to identify periodontitis and depression, respectively. Daily alcohol consumption in the past year was classified into three levels: low (1 drink or less), moderate (between 1 and 3 drinks), and heavy drinking (4 drinks or more), while smoking was defined as having smoked at least 100 cigarettes in one's lifetime. Then, the logistic regression combined with interaction models were used to analyze the independent and combined effects of smoking, drinking and depression on periodontitis risk. RESULTS: The results indicated a statistically significant multiplicative interaction between smoking and depression in relation to the development of periodontitis, both in the overall population (P = 0.03) and among male participants (P = 0.03). Furthermore, among individuals experiencing depression, smoking was found to significantly increase the prevalence of periodontitis by 129% in the younger age group compared to non-smokers (odds ratio [OR]: 2.29; 95% confidence interval [CI]: 1.10 to 4.76). However, the interaction between smoking and alcohol consumption was only significant among females (P < 0.05). There was a dose-dependent relationship between drinking frequency and smoking on periodontitis prevalence. In the smoking population, occasional drinking (OR: 1.70; 95% CI: 1.22 to 2.37) and regular drinking (OR: 2.28; 95% CI: 1.68 to 3.11) significantly increased the prevalence of periodontitis compared to individuals without these two factors. CONCLUSION: These results suggested that there were interactive effects between smoking, drinking and depression on periodontitis risk and policies aimed at healthy behaviours and mental health may be beneficial for our oral health.

[Clinical analysis of cytomegalovirus infection-associated hemophagocytic lymphohistiocytosis in five patients without underlying diseases].

The clinical data of five patients [one male and four female; median age: 31 (21-65) years] with cytomegalovirus (CMV)-induced hemophagocytic lymphohistiocytosis (HLH) diagnosed and treated in the First Affiliated Hospital of Nanjing Medical University were retrospectively analyzed from January 2011 to December 2020. None of the patients had any underlying disease, and all were immunocompetent. The main clinical presentations were fever in all five patients, splenomegaly in four, enlarged lymph nodes in two, liver enlargement in one, and rash in three. Pulmonary infection was found in three patients, two of whom developed respiratory failure. Two patients had jaundice. Central nervous system symptoms and gastrointestinal bleeding were observed in one case. All patients received glucocorticoids and antiviral therapy. One patient was treated with the COP (cyclophosphamide+vincristine+prednisone) chemotherapy regimen after antiviral therapy failed and he developed central nervous system symptoms. After treatment, four patients achieved remission, but the fifth pregnant patient eventually died of disease progression after delivery. CMV-associated HLH in an immunocompetent individual without underlying diseases is extremely rare, and most patients have favorable prognosis. Antiviral therapy is the cornerstone of CMV-HLH treatment.

[Analysis of the change in human resources of centers for disease control and prevention in different regions of China from 2010 to 2020].

Objective: To analyze the change in human resources within China's Centers for Disease Control and Prevention (CDC) from 2010 to 2020. Methods: The self-reported information from provincial, prefectural (city), and county (district) levels of China's CDC, covering employee counts, staff composition, professional qualifications, educational backgrounds, technical titles, and tenure, were extracted from the China Disease Prevention and Control Information System. The demographic context was provided by the annual population figures from the China Statistical Yearbook (2010-2020). The profile of CDC personnel was described, and the average annual percentage rate change (AAPC), average annual percentage rate change (APC), human resource agglomeration degree (HRAD) and the difference between HRAD and population agglomeration degree (PAD) were calculated. The Joinpoint regression model was used to analyze the time trend. Results: The decade under review witnessed a net increase of 17 300 active and 18 300 enrolled personnel in the CDC, surpassing the national population growth rate with AAPCs of 0.93% and 1.03%, respectively. This upward trajectory was statistically significant (P<0.05). The ratio of disease control personnel per 10 000 population escalated from 1.14 to 1.21. An initial decline in active CDC workforce density (from 1.31 to 1.27 per 10 000 population between 2010 and 2017) was followed by an increase (from 1.28 to 1.37 between 2018 and 2020), with APCs of -0.40% and 3.73%, respectively. The proportion of professional and technical staff in 2019 was highest in the eastern region (86.01%), followed by the western (83.75%) and central regions (79.54%). The period also saw an enhancement in the average academic degree (from 1.91 to 2.43 points) and professional title scores (from 1.39 to 1.53 points) of CDC personnel. While the average tenure in the eastern and western regions showed a slight decline, the central region experienced an increase, with HRAD values indicating a higher concentration in the eastern and central regions compared to the western region. The HRAD-PAD discrepancy revealed a negative value in the eastern region, nearing zero in the central and western regions. Conclusion: Between 2010 and 2020, China's CDC experienced notable growth in human resources and underwent structural optimization, albeit with significant regional disparities in concentration.

[Attach importance to the orderly development of different corneal transplant procedures].

There are various surgical methods for corneal transplantation, each requiring precise treatment tailored to the characteristics and different layers of corneal opacity or lesions. These layers include the corneal epithelium, stroma (lamellar), and corneal endothelium, with options for full-thickness (penetrating) corneal transplantation or artificial corneal transplantation. However, a current issue in clinical practice is that, regardless of the degree of corneal disease, the availability of corresponding eye bank support, or surgical conditions, classic penetrating (full-thickness) corneal transplantation is universally performed. Alternatively, there is a trend toward adopting technically demanding procedures such as endothelial transplantation and artificial corneal transplantation. This trend has led to increased postoperative complications and the wastage of corneal donor materials. Choosing the appropriate corneal transplant procedure can offer advantages such as preserving more healthy corneal tissue, conserving corneal donors, facilitating rapid vision recovery, and minimizing the risk of immune rejection. Corneologists need to master the indications for various corneal transplant surgeries and systematically perform different corneal transplant procedures based on the surgeon's skills, hospital conditions, and eye bank conditions. This approach aims to enhance the success rate of the surgery.

[Intraoperative optical coherence tomography guided precise corneal suture in the treatment of acute keratoconus].

Objective: This study aimed to observe the clinical efficacy of precise suturing of posterior elastic layer fissures guided by intraoperative optical coherence tomography (OCT) in conjunction with anterior chamber puncture and drainage, and corneal thermokeratoplasty for the treatment of severe acute edematous keratoconus. Methods: Non-randomized controlled trial. Data were collected for a study involving 31 cases of acute edematous keratoconus patients who underwent surgical treatment at the Shandong Eye Hospital between June 2017 and July 2021. Among them, there were 30 male and 1 female patients, with an age range of 11 to 32 years and a mean age of (19.80±5.80) years. Eighteen patients in the study group underwent precise suturing of posterior elastic layer fissures guided by intraoperative OCT, in combination with anterior chamber puncture and drainage, and corneal thermokeratoplasty. Thirteen patients in the control group did not undergo suturing. Preoperative visual acuity, corneal edema diameter, corneal thickness, and posterior elastic layer fissure length were collected. Evaluation was performed using slit lamp microscopy, anterior segment OCT, and other methods to assess the time of initial postoperative corneal edema resolution and closure of the posterior elastic layer fissure. Deep lamellar keratoplasty was performed 2 to 4 weeks after edema resolution, and the corneal bed scar repair and visual acuity of the two groups were compared. Results: In the suturing group, the corneas of all 18 patients were accurately sutured to the deep stromal layer near the posterior elastic layer. The time for corneal edema resolution was 2.50 (1.00, 6.25) days in the suturing group and 7.00 (6.00, 10.50) days in the control group. The fissure healing time was 7.50 (7.00, 12.00) days in the suturing group and 14.00 (9.00, 14.00) days in the control group. The differences were statistically significant (all P<0.05). After 2 weeks, the central corneal thickness decreased to (529.80±174.50) µm in the suturing group and (612.00±205.12) µm in the control group. The suturing group showed accurate corneal suturing to the deep stromal layer near the posterior elastic layer, resulting in central corneal flattening, closure of voids in the stroma, and a significant decrease in corneal thickness. All 18 patients in the suturing group successfully completed deep lamellar keratoplasty, with 6 cases (6/18) experiencing mild graft bed leakage during surgery but without affecting the deep lamellar keratoplasty. One year postoperatively, the visual acuity (logarithm of the minimum resolution angle) was 0.23±0.12 in the suturing group and 0.33±0.11 in the control group, with a statistically significant difference (P<0.05). Conclusions: In the treatment of severe acute edematous keratoconus, precise suturing of posterior elastic layer fissures guided by intraoperative OCT, in conjunction with anterior chamber puncture and drainage, and corneal thermokeratoplasty, can rapidly alleviate corneal edema and promote the healing of posterior elastic layer fissures. This approach achieves better visual outcomes for subsequent lamellar keratoplasty surgeries. The use of intraoperative OCT guidance allows accurate positioning of the posterior elastic layer fissure in terms of location, direction, and depth of corneal stromal voids, thereby assisting surgeons in precise suturing.

The Effectiveness of Interventions for Reducing Loneliness Among Chinese Older Adults: A Systematic Review and Meta-Analysis.

This review assesses interventions to reduce loneliness in Chinese older adults, analyzing 36 studies involving 3965 participants. Focusing on individuals aged 50 and over, the meta-analysis reveals a significant overall effect size (Hedges' g = 0.937, 95% CI [0.71,1.16], p<0.001), highlighting the effectiveness of psychological and mixed-method approaches. Despite promising results, methodological concerns suggest cautious interpretation. Future research should aim to refine intervention quality and examine the impact of technology-supported methods on loneliness.

DNA sensing in the pathological process of ischemic stroke.

The innate immune response plays an important role in the pathological process of ischemic stroke. Increasing evidence suggests that the inflammatory response triggered by the innate immune system hinders neurological and behavioural recovery after stroke. The perception of abnormal DNA and its downstream effects are an essential part of the innate immune system. The abnormal DNA is the major inducing factor for innate immune response and is sensed by a series of DNA sensors. In this review, we discussed the multiple roles of DNA sensing in the pathological process of ischemic stroke, with a special focus on DNA sensors Toll-like receptor 9 (TLR9), absent in melanoma 2 (AIM2) and cyclic GMP-AMP synthase (cGAS).

Transient depletion of macrophages alters local inflammatory response at the site of disc herniation in a transgenic mouse model.

OBJECTIVE: Macrophages are abundantly detected at sites of disc herniation, however, their function in the disease progression is unclear. We aim to investigate the functions of macrophages in acute disc herniation using a macrophage Fas-induced apoptosis (MaFIA) transgenic mouse strain. METHOD: To transiently deplete macrophages, a dimerizer, AP20187, or vehicle solution was administered via intraperitoneal injection to MaFIA mice immediately, day 1 and 2 after annular puncture induced disc herniation. Local infiltrated tissues at disc hernia and DRGs at corresponding levels were harvested to analyze immune cells and neuroinflammation on postoperative day (POD) 6 by flow cytometry and/or immunostaining. Mouse spines were harvested to analyze structures of degenerated discs and adjacent vertebrae and to assess osteoclast activity by histology and tartrate-resistant acid phosphatase (TRAP) staining on POD 6, 13, and 20, respectively. RESULTS: On POD 6, abundant macrophages were confirmed at disc hernia sites. Compared to vehicle control, AP20187 significantly reduced GFP+ cells in blood, spleen, and local inflammatory tissue. At disc hernia sites, AP20187 markedly reduced macrophages (CD11b+, F4/80+, GFP+CD11b+, CD11b+F4/80+) while increasing neutrophils and B cells. Transient macrophage depletion decreased ectopic bone formation and osteoclast activity in herniated discs and adjacent cortical bones for up to 20 days post herniation. Disc herniation elevated expressions of TNF-α, IL-6, substance P, calcitonin gene-related peptide, accompanied by increasing GFP+, CD11b+ and F4/80+ macrophages. Macrophage depletion did not attenuate these markers of neuroinflammation. CONCLUSIONS: Transient depletion of macrophages altered local inflammatory response at the site of disc herniation.

Prevalence and risk factors of erectile dysfunction in COVID-19 patients: a systematic review and meta-analysis.

PURPOSE: Studies have found that erectile dysfunction (ED) may be a short-term or long-term complication in coronavirus disease 2019 (COVID-19) patients, but no relevant studies have completed a pooled analysis of this claim. The purpose of the review was to comprehensively search the relevant literature, summarize the prevalence of ED in COVID-19 patients, assess risk factors for its development, and explore the effect of the COVID-19 infection on erectile function. METHODS: Medline, Embase, and the Cochrane Library was performed from database inception until April 14, 2022. Heterogeneity was analyzed by χ2 tests and I2 was used as a quantitative test of heterogeneity. Subgroup analyses, meta-regression, and sensitivity analyses were used to analyze sources of heterogeneity. RESULTS: Our review included 8 studies, 4 of which functioned as a control group. There were 250,606 COVID-19 patients (mean age: 31-47.1 years, sample size: 23-246,990). The control group consisted of 10,844,200 individuals (mean age: 32.76-42.4 years, sample size 75-10,836,663). The prevalence of ED was 33% (95% CI 18-47%, I2 = 99.48%) in COVID-19 patients. The prevalence of ED based on the international coding of diseases (ICD-10) was 9% (95% CI 2-19%), which was significantly lower than the prevalence of ED diagnosed based on the International Index of Erectile Function (IIEF-5) (46%, 95% CI 22-71%, I2 = 96.72%). The pooling prevalence of ED was 50% (95% CI 34-67%, I2 = 81.54%) for articles published in 2021, significantly higher than that for articles published in 2022 (17%, 95% CI 7-30%, I2 = 99.55%). The relative risk of developing ED was 2.64 times in COVID-19 patients higher than in non-COVID-19 patients (RR: 2.64, 95% CI 1.01-6.88). The GRADE-pro score showed that the mean incidence of ED events in COVID-19 patients was 1,333/50,606 (2.6%) compared with 52,937/844,200 (0.4%) in controls; the absolute impact of COVID-19 on ED was 656/100,000 (ranging from 4/100,000 to 2352/100,000). Anxiety (OR: 1.13, 95% CI 1.03-1.26, I2 = 0.0%) in COVID-19 patients was a risk factor for ED. CONCLUSION: COVID-19 patients have a high risk and prevalence of ED, mainly driven by anxiety. Attention should be paid to patient's erectile functioning when treating COVID-19.

Anterolateral thigh perforator flap made by customized 3D-printing fabrication of fixed positioning guide for oromaxillofacial reconstruction: a preliminary study.

BACKGROUND: Oromaxillofacial carcinomas frequently result in serious tissue defect due to enlarged resection for treating their extensive invasion, which require challenging reconstruction. Three-dimensional (3D) printing is an advanced technology which has greatly promoted the progress of craniomaxillofacial reconstructive surgery. This present study aimed to investigate the advantages of anterolateral thigh (ALT) perforator flap manufactured by 3D printing fixed positioning guide template in curing oromaxillofacial defect. MATERIAL AND METHODS: Twenty patients with oromaxillofacial defects resulted from severe primary malignant tumors were divided into experimental group assisted by digital technique (n=8) and controlled group conventionally aided by ultrasound (n=12). The therapeutic effectiveness, flap preparation time, amount of bleeding, deviation of perforator vessel location, aesthetic satisfaction of donor site, postoperative complications, adverse symptom of flap, and LEFS scores were compared. RESULTS: For experimental group, flap preparation time was significantly shorter; and it has obviously less bleeding, minor deviation of perforator vessel location, and better aesthetic satisfaction of donor site (P<.001). There was no statistical difference in postoperative complications and LEFS scores between two groups (P>.05). CONCLUSIONS: The study suggests 3D printing template of fixed positioning guide provides a brand-new method for orienting perforated vessels of ALT flap, which is more accurate in clinical application. It can improve the operative efficacy, and increase the successful rate of operation as well.

[Radiographic diagnosis of distal fibula avulsion fractures: Comparison of ankle X-ray and three-dimensional reconstruction of CT].

OBJECTIVE: To investigate the difference in sensitivity between X-ray and three-dimensional reconstruction of computed tomography (3D-CT) for the diagnosis of distal fibular avulsion fracture, and the radiographic presentation of the ossicle. METHODS: From January to October 2018, 92 patients with distal fibular avulsion fracture were visited for surgical treatment in Department of Sports Medicine, Peking University Third Hospital, and 60 cases were finally enrolled according to the inclusion and exclusion criteria. Intraoperative detection was regarded as the gold standard, and the diagnostic sensitivity of preoperative ankle X-ray and 3D-CT for the distal fibular avulsion fractures was statistically determined. The ossicle maximum diameter as well as the degree of its displacement were also measured. On 3D-CT, the distance from the ossicle center point to the anterior fibular tuberosity (a), the distance to the fibular tip (b), and the a/b value was used to present the ossicle displacement. RESULTS: Among the 60 patients, 36 and the 52 patients were correctly detected by X-ray and 3D-CT, respectively, and the sensitivities was 60.0% and 86.7%, respectively (P=0.004). The mean diameter of the ossicle on X-ray and 3D-CT was (9.2±3.9) mm and (10.5±3.2) mm, respectively. The mean distance from the ossicle center to the anterior fibular tuberosity (a) was (17.5±3.6) mm and the mean distance to the fibular tip (b) was (17.4±4.8) mm, with mean a/b values of 1.1±0.7. The intraclass correlation coefficients (ICC) for each measurement ranged from 0.891-0.998 with a high degree of consistency. CONCLUSION: Compared with X-ray, 3D-CT has higher sensitivity in diagnosing distal fibular avulsion fractures, can help clinicians evaluate ossicle's location and choose surgical methods, and is recommended to be performed in patients with suspected distal fibula avulsion fractures in clinical practice.

[Efficacy and influencing factors of immunotherapy combined with chemotherapy and bevacizumab in patients with non-small cell lung cancer after epidermal growth factor receptor tyrosine kinase inhibitors treatment failure].

Objective: To investigate the efficacy and influencing factors of immunotherapy combined with chemotherapy and bevacizumab in patients with non-small cell lung cancer (NSCLC) who failed epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) treatment. Methods: A retrospective analysis was made on the clinical data of 60 NSCLC patients who were treated with immunotherapy combined with chemotherapy and bevacizumab after EGFR-TKIs treatment failure in the Affiliated Cancer Hospital of Shandong First Medical University from January 2019 to March 2022. Patients were followed up by telephone or outpatient review up to October 1, 2022, with a median follow-up of 8.2 months (95%CI: 7.1-9.3). All 60 patients were followed up. The response evaluation criteria in solid tumors were used to evaluate the short-term efficacy. The adverse reactions of patients were evaluated according to the common terminology criteria for adverse events. The survival curve was drawn by Kaplan-Meier method. Cox proportional hazard regression models were utilized to analyze the influencing factors of progression-free survival (PFS). Results: Among the 60 NSCLC patients, 22 were males. The age ranged from 41 to 75 years, with a median age of 61 years. Eleven patients had partial response, 19 patients had stable disease and 30 patients had progressive disease. The median PFS was 8.2 months (95%CI: 7.2-9.2). The median PFS of patients with low expression of programmed death receptor-ligand 1 (PD-L1) [Tumor cell Proportion Score (TPS)<1%], moderate expression of PD-L1 (1%≤TPS≤49%), and high expression of PD-L1 (TPS≥50%) were 6.4 (95%CI: 4.8-8.0), 8.3 (95%CI: 7.3-9.3) and 10.6 months (95%CI: 7.2-14.1), respectively, and there were statistically significant differences (χ2=13.58, P<0.001). Multivariate Cox proportional risk regression model analysis showed that age>65 years old (HR=4.017, 95%CI: 1.468-10.992, P=0.007) was a risk factor for PFS in NSCLC patients who received immunotherapy combined with chemotherapy and bevacizumab after EGFR-TKIs treatment failure. Moderate expression of PD-L1 (HR=0.360, 95%CI: 0.139-0.930, P=0.035) and high expression of PD-L1 (HR=0.155, 95%CI: 0.039-0.625, P=0.009) were protective factors for PFS. Most of the treatment-related adverse reactions in the whole group were grade 1-2, including bone marrow suppression (n=24), nausea (n=25), decreased appetite (n=24), fatigue (n=22), vomiting (n=18), abnormal liver function (n=17), blood creatinine increased (n=10), and so on. These were tolerated by the patients. Conclusions: NSCLC patients who failed EGFR-TKIs treatment can tolerate adverse reactions related to immunotherapy combined with chemotherapy and bevacizumab treatment. PFS is significantly prolonged in those aged≤65 years and those with moderate and high expression of PD-L1.

[Analysis of the status of excess heart age and its risk factors among residents aged 35 to 64 years in China].

Objective: To analyze the status of excess heart age and its risk factors among Chinese residents aged 35 to 64 years. Methods: The study subjects were Chinese residents aged 35 to 64 years who completed the heart age assessment by WeChat official account "Heart Strengthening Action" through the internet from January 2018 to April 2021. Information such as age, gender, body mass index (BMI), blood pressure, total cholesterol (TC), smoking history, and diabetes history was collected. The heart age and excess heart age were calculated according to the characteristics of individual cardiovascular risk factors and the heart aging was defined as excess heart age≥5 years and 10 years respectively. The heart age and standardization rate were calculated respectively based on the population standardization of the 7th census in 2021.CA trend test was used to analyze the changing trend of excess heart age rate and population attributable risk (PAR) was used to calculate the contribution of risk factors. Results: The mean age of 429 047 subjects was (49.25±8.66) years. The male accounted for 51.17% (219 558/429 047) and the excess heart age was 7.00 (0.00, 11.00) years. The excess heart age rate defined by excess heart age≥5 years and ≥10 years was 57.02% (the standardized rate was 56.83%) and 38.02% (the standardized rate was 37.88%) respectively. With the increase of the age and number of risk factors, the excess heart age rate of the two definitions showed an upward trend according to the result of the trend test analysis (P<0.001). The top two risk factors of the PAR for excess heart age were overweight or obese and smoking. Among them, the male was smoking and overweight or obese, while the female was overweight or obese and having hypercholesterolemia. Conclusion: The excess heart age rate is high in Chinese residents aged 35 to 64 years and the contribution of overweight or obese, smoking and having hypercholesterolemia ranks high.

[Characteristics of primary ocular symptoms in children with optic pathway glioma at different ages].

Objective: To investigate the characteristics of initial ocular symptoms in children with optic pathway glioma (OPG) at different age stages. Methods: A retrospective case series study was conducted. Clinical data of 16 children with OPG who were diagnosed and treated in the Department of Ophthalmology, Beijing Children's Hospital, Capital Medical University from April 2017 to July 2021 were collected. The initial ocular symptoms, clinical manifestations of the eyes and nervous system, imaging and histopathological features were analyzed, and the differences in initial ocular symptoms between infants and young children aged≤36 months and older children aged>36 months were compared. Results: Of all 16 children included, 9 were male and 7 were female. The onset age was 15.0 (6.3, 56.5) months, and the diagnosis age was 48.0 (11.3, 78.0) months. There were 11 infants and young children, and 5 older children. Eye symptoms were the initial manifestation in 11 cases, including 8 cases of infants and young children (5 cases presented with irregular nystagmus, 2 cases with strabismus, and 1 case with failure to chase visual target), and 3 cases of older children (2 cases presented with decreased vision and 1 case with optic disc edema). The imaging findings showed that optic chiasm-involved OPG accounted for the highest proportion, with 3 cases in older children and 8 cases in infants and young children. Among the 8 children with optic chiasm-involved OPG who underwent surgical treatment, 5 were diagnosed with pilocytic astrocytoma according to histopathological results. Seven children had useful vision saved after treatment, and 1 child had visual loss accompanied by cognitive impairment due to surgery after 4 years of nystagmus. Conclusion: OPG in children often manifests as initial ocular symptoms, with irregular nystagmus being more common in infants and young children, and vision loss being the main symptom in older children.

[Application of intraoperative optical coherence tomography in deep lamellar keratoplasty].

Objective: To evaluate the clinical application value of intraoperative optical coherence tomography (iOCT) in deep anterior lamellar keratoplasty (DALK) using the big-bubble technique to bare Descemet's membrane. Methods: Retrospective case series. Clinical data of 92 patients (92 eyes) with monocular stromal corneal diseases who underwent big-bubble DALK in the Eye Hospital of Shandong First Medical University from January 2020 to August 2021 were collected. There were 53 males and 39 females. The average age was (53.2±16.0) years old. All patients underwent iOCT scanning to determine the location and depth of the injection needle after initial removal of the corneal lesion, to observe the integrity of the recipient bed, Descemet's membrane, after complete lesion removal, and to observe the adhesion between the corneal graft and the recipient bed and check folds on the recipient bed after suturing of the corneal graft. The intraoperative perforation of Descemet's membrane, postoperative thickness of the cornea and the recipient bed, visual acuity, and corneal astigmatism were recorded. Results: By iOCT, the thickness of the recipient bed was found to be about 1/2 of the corneal thickness and relatively uniform in all directions in 62 eyes (67.4%), so the sterile air was injected from the center of the recipient bed to separate it from the stromal layer. In 30 eyes (32.6%) with an uneven thickness of the recipient bed, the sterile air was injected from the paracentral area of the recipient bed. Under the guidance of iOCT scanning, 89 eyes (96.7%) did not experience any perforation of Descemet's membrane during surgery. The Descemet's membrane folds in the central 5-mm area of the recipient bed was observed and flattened in 20 eyes with the assistance of iOCT scanning. The postoperative corneal thickness was (578.95±108.26) µm, and the recipient bed thickness was (36.06±23.11) µm. The best corrected visual acuity of all patients at 6 months after surgery was 0.57±0.25 logMAR, which was significantly better than that before surgery (1.61±1.27 logMAR; P<0.001). The average corneal astigmatism at 6 months after surgery was (2.72±2.44) diopters. Conclusions: The application of iOCT scanning in DALK surgery assisted by the big-bubble method can provide safe guidance for surgeons to adopt correct surgical procedures, decrease the risk of Descemet's membrane perforation, reduce the recipient bed folds, and facilitate corneal interlayer adhesion, thereby improving the visual prognosis.

[Femtosecond laser-assisted minimally invasive lamellar keratoplasty for advanced keratoconus].

Objective: To evaluate the initial safety and efficacy of femtosecond laser-assisted minimally invasive lamellar keratoplasty (FL-MILK) for advanced keratoconus. Methods: It was a case series study. Patients with advanced keratoconus who underwent FL-MILK between August 2017 and April 2020 at Shandong Eye Hospital were prospectively included. The femtosecond laser was used to create an intrastromal pocket in the recipient cornea and a lamellar cornea in the donor. The lamellar cornea was then gently inserted into the intrastromal pocket through the incision and flattened. Clinical measurements included best-corrected visual acuity, 3-mm anterior corneal mean keratometry, anterior and posterior central corneal elevation, central corneal thickness, corneal biomechanics, and endothelial cell density. The follow-up was conducted at 1 month, 12 months, and 24 months after the operation. Results: There were 33 patients (35 eyes) in the study. Twenty-six patients were male and 7 patients were female. The mean age was (20.34±5.24) years old. All patients completed 12 months of follow-up, and 25 patients (27 eyes) completed 24 months of follow-up. No epithelial ingrowth, infection, or allogeneic rejection was observed. Compared with the preoperative data, the anterior central corneal elevation significantly decreased (P<0.001), the mean keratometry significantly decreased (P<0.05), and the central corneal thickness significantly increased (P<0.001). The corneal biomechanical strength was significantly improved, with the deformation amplitude ratio at 2.0 mm decreasing from 1.39±0.14 preoperatively to 1.21±0.10 at 24 months postoperatively (P<0.001) and the stiffness parameter at the first applanation increasing from 41.49±11.47 preoperatively to 88.41±18.17 at 24 months postoperatively (P<0.001). There were no significant changes in the mean best-corrected visual acuity, posterior corneal elevation, mean spherical equivalent, and endothelial cell density (all P>0.05). Conclusions: FL-MILK may be a feasible option for advanced keratoconus. This procedure may provide a new resolution for keratoconus.

[Analysis of factors affecting the quality of donor corneal endothelial cells].

Objective: To explore the factors influencing the quality of donor corneal endothelium. Methods: A retrospective case series study was conducted. Data from 568 donor corneas obtained from the Shandong Eye Bank between July 1, 2020, and June 30, 2021, were collected for analysis. The corneal endothelium of the donor corneas was observed using corneal endothelial microscopy to assess corneal endothelial cell density (ECD), coefficient of variation, and hexagonal cell ratio (HEX). Relevant factors of corneal donors were collected, including gender, age, cause of death, season of death, time from death to corneal retrieval, and methods of corpse preservation, to investigate their impact on the quality of donor corneal endothelium. The age factor was divided into five age groups: 0-20 years, 21-40 years, 41-60 years, 61-80 years, and >80 years. The time of corneal retrieval was divided into three periods based on the time elapsed since the donor's death: <6 hours, 6-12 hours, and >12 hours. The relationship between these factors and corneal endothelial conditions was analyzed. Results: The 568 donor corneas were obtained from 288 donors, including 225 males (78.13%) and 63 females (21.87%). The mean age was 51.77±18.48 years. The causes of death among donors were as follows: cardiovascular diseases 54.58% (275 individuals), cancer 17.96% (74 individuals), organ failure 14.26% (49 individuals), and accidents 13.20% (64 individuals). The mean time of corneal retrieval after donor death was 140 (76, 400) minutes (ranging from 30 minutes to 45 hours). Among the 145 corneas (25.53%) that had their initial corneal endothelial microscopy examination, the images were not clear, and after thorough rewarming, 106 corneas (18.7%) still had unclear images and could not be analyzed. Among the 462 corneas (81.3%) with clear images, the ECD was (2 602.23±318.40) cells/mm², the coefficient of variation was 36.61%±4.81%, and the HEX was 52.73%±7.15%. The ECD of corneas from older donors was lower compared to younger donors, and the differences between age groups were statistically significant (P<0.001). Corneas from donors who died due to accidents had a higher ECD [(2 829.88±313.90) cells/mm²] compared to those who died from cancer, cardiovascular diseases, and organ failure, and the differences were statistically significant (P<0.001). The ECD was highest when corneas were retrieved within 6 hours after death, and the difference was statistically significant (P<0.001). Older donors had higher coefficients of variation but lower HEX values (both P<0.05). Corneas retrieved after a longer time from death had higher coefficients of variation, and the difference was statistically significant (P<0.05), but there was no statistically significant difference in HEX (P>0.05). Organ failure, cryopreservation, and corneal retrieval time >12 hours were risk factors for unclear corneal endothelial imaging (all P<0.001). Among the 136 corneal endothelial images (23.94%), circular, oval, or band-shaped dark areas were observed, and corneas with dark areas had lower ECD (P<0.05). The longer the time elapsed from death to corneal retrieval, the more dark areas were observed (P<0.001). The presence of dark areas did not affect the coefficient of variation and HEX (P>0.05). Conclusion: Advanced donor age, death due to chronic diseases, longer time elapsed from death to corneal retrieval, and cryopreservation of the body lead to a decrease in the quality of donor corneal endothelium.

[A multicenter clinical trial of collar-button type keratoprosthesis implantation for the treatment of corneal blindness in high-risk transplantation].

Objective: To evaluate the efficiency and safety of collar-button type keratoprosthesis (c-bKPro) implantation for corneal blindness in high-risk transplantation in China. Methods: It was a case series study. High-risk corneal blind patients who planned to undergo c-bKPro implantation were prospectively and continuously enrolled in the Eye Hospital of Shandong First Medical University, Ophthalmology Division of Chinese PLA General Hospital, Zhongshan Ophthalmic Center, Department of Ophthalmology in Eye & ENT Hospital of Fudan University, and Eye Hospital of Wenzhou Medical University from July 2019 to January 2020. The cure for blindness and surgical success were assessed based on visual acuity (VA)≥0.05. The complications and keratoprosthesis retention rate were recorded to determine the safety of the surgery. Results: Thirty-seven subjects (eyes) were included, of which 32 were male and 5 were female, aged 27 to 72 years old. The indications of c-bKPro implantation were corneal graft failure (21 eyes, 56.8%), chemical injury (8 eyes, 21.6%), thermal burn (5 eyes, 13.5%), unexplained corneal opacity (2 eyes, 5.4%), and corneal perforation (1 eye, 2.7%). Two patients withdrew from the clinical trial at 3 months postoperatively. Thirty-five patients were followed up for 6 months, and 31 were followed up for 12 months. The VA was ≥0.05 in 83.8% of eyes at 6 months and in 81.8% of eyes at 12 months. Among the 11 eyes diagnosed with concurrent glaucoma, 6 eyes achieved a VA of ≥0.05. At 12 months, the c-bKPro retention rate was 100%. The surgical complications included retroprosthetic membrane formation (5 eyes, 16.1%), persistent corneal epithelial defects (5 eyes, 16.1%), macular edema (4 eyes, 12.9%), new-onset glaucoma (4 eyes, 12.5%; including one eye withdrawn from the study at 3 months), sterile corneal melting (2 eyes, 6.5%), sterile vitritis (1 eye, 3.2%), and infectious keratitis (1 eye, 3.2%). Conclusions: C-bKPro implantation is an effective and safe option for treating corneal blindness in high-risk transplantation in China. Improved visual outcomes could be achieved in most cases, with a relatively low incidence of postoperative complications.

Genome-wide analysis of mitochondrial DNA copy number reveals loci implicated in nucleotide metabolism, platelet activation, and megakaryocyte proliferation.

Mitochondrial DNA copy number (mtDNA-CN) measured from blood specimens is a minimally invasive marker of mitochondrial function that exhibits both inter-individual and intercellular variation. To identify genes involved in regulating mitochondrial function, we performed a genome-wide association study (GWAS) in 465,809 White individuals from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank (UKB). We identified 133 SNPs with statistically significant, independent effects associated with mtDNA-CN across 100 loci. A combination of fine-mapping, variant annotation, and co-localization analyses was used to prioritize genes within each of the 133 independent sites. Putative causal genes were enriched for known mitochondrial DNA depletion syndromes (p = 3.09 × 10-15) and the gene ontology (GO) terms for mtDNA metabolism (p = 1.43 × 10-8) and mtDNA replication (p = 1.2 × 10-7). A clustering approach leveraged pleiotropy between mtDNA-CN associated SNPs and 41 mtDNA-CN associated phenotypes to identify functional domains, revealing three distinct groups, including platelet activation, megakaryocyte proliferation, and mtDNA metabolism. Finally, using mitochondrial SNPs, we establish causal relationships between mitochondrial function and a variety of blood cell-related traits, kidney function, liver function and overall (p = 0.044) and non-cancer mortality (p = 6.56 × 10-4).