AIM:To analyze the effect of conbercept treatment on different types of macular edema secondary to retinal vein occlusion(RVO-ME)using optical coherence tomography(OCT)images.METHODS: This retrospective study included patients who first received conbercept injections for RVO-ME at Yijishan Hospital of Wannan Medical College from December 1, 2017, to March 31, 2022. Data on disease duration, age, hypertension, OCT images, central macular thickness(CMT), and best-corrected visual acuity(BCVA)were collected before and at 4-6 wk after treatment. Patients were divided into 4 groups according to different types of macular edema: cystoid macular edema(CME), sponge-like diffuse retinal thickening(SDRT), serous retinal detachment(SRD), and mixed type(FULL). Changes in CMT and visual acuity before and after treatment were compared among the groups to analyze differences in the effect of conbercept treatment on different ME types, and the effect of baseline CMT and visual acuity on post-treatment visual acuity.RESULTS: Totally 139 patients(139 eyes)were classified as having macular edema, including 62 males(44.6%)and 77 females(55.4%), with a mean age of 58.9±10.9 years, and they were divided into 4 groups based on different types of macular edema, including 54 cases(54 eyes)(mean age 59.6±11.1 years)in the CME group, 23 cases(23 eyes; mean age 56.6±10.2 years)in the SDRT group, 22 cases(22 eyes; mean age 57.8±12.0 years)in the SDR group, and 40 cases(40 eyes; mean age 60.0±10.7 years)in the FULL group. There were no significant differences in the duration of disease or age between groups(P>0.05). There was a significant difference in preoperative CMT between groups(P=0.01, one-way ANOVA), with the CMT in the FULL group being significantly greater than that in the SDRT group(P=0.03). There were no significant differences in pre-treatment visual acuity between the four groups(P=0.26). After conbercept treatment, the macular central recess thickness was reduced and visual acuity was improved in all four groups, among which the CMT in the CME and FULL groups was reduced significantly compared with the other two groups(P<0.05), and the visual acuity in the CME and SRD groups was improved significantly compared with the other two groups(P<0.05). Postoperative visual acuity was negatively correlated with preoperative CMT(P=0.044)and positively correlated with preoperative visual acuity(P<0.01).CONCLUSION:The efficacy of intravitreal conbercept in the treatment of RVO and macular edema may be related to the type of edema observed on OCT images, in which the efficacy is best in patients with CME but poor in patients with SDRT.

Objective:Using methylation characteristics of human genes to construct machine learning predictive models for screening cervical cancer and precancerous lesions.Methods:Human DNA methylation detection was performed on 224 cervical exfoliated cell specimens from the Cancer Hospital of the Chinese Academy of Medical Sciences, Tianjin Central Hospital of Gynecology Obstetrics, Xinmi Maternal and Child Health Hospital of Henan Province, West China Second Affiliated Hospital of Sichuan University, and Heping Hospital Affiliated to Changzhi Medical College collected during April 2014 and March 2015. The hypermethylated gene fragments related to cervical cancer were selected by high-density, high-association, and hypermethylated gene fragment screening and the LASSO regression algorithm. Taking cervical intraepithelial neoplasia grade 2 (CIN2) or more severe lesions as the research outcome, machine learning predictive models based on the random forest (RF), naive Bayes (NB), and support vector machine (SVM) algorithm, respectively, were constructed. A total of 144 outpatient specimens were used as the training set and 80 cervical exfoliated cell specimens from women participating in the cervical cancer screening program were used as the test set to verify the predictive models. Using histological diagnosis results as the gold standard, the detection efficacy for CIN2 or more severe lesions of the three machine learning predictive models were compared with that of the human papilloma virus (HPV) detection and cytological diagnosis.Results:In the training set of 144 cases, there were 34 cases of HPV positivity, with a positive rate of 23.61%. Cytologically, there were 37 cases diagnosed as no intraepithelial lesion or malignancy (NILM), and 107 cases diagnosed as atypical squamous cells of undetermined significance (ASC-US) or above. Histologically, there were 28 cases without cervical intraepithelial neoplasia or benign cervical lesions, 31 cases of CIN1, 18 cases of CIN2, 31 cases of CIN3, and 36 cases of squamous cell carcinoma. Seven hypermethylated gene fragments were selected from 45 genes, and three machine learning prediction models based on the RF, NB, and SVM algorithm, respectively, were constructed. In the validation set of 80 cases, there were 28 cases of HPV positivity, with a positive rate of 35.00%. Cytologically, there were 65 cases diagnosed as NILM and 15 cases as ASC-US or above. Histologically, there were 39 cases without cervical intraepithelial neoplasia or benign cervical lesions, 10 cases of CIN1, 10 cases of CIN2, 11 cases of CIN3, and 10 cases of squamous cell carcinoma. In the validation set, the area under the curve (AUC) values of the RF model, NB model, SVM model, HPV detection, and cytological diagnosis of CIN2 or above were 0.90, 0.88, 0.82, 0.68, and 0.45, respectively. The DeLong test showed that there was no statistically significant difference in the AUC values between the RF, NB, and SVM models (all P＞0.05), and the AUC values of the RF and NB models were higher than that of HPV detection (both P＜0.01), and the AUC values of the RF, NB, and SVM models were higher than that of cytological diagnosis (all P＜0.01). Compared with the NB model, the sensitivity of the RF model was similar (80.65% vs. 77.42%), but the specificity of the NB model was much higher than that of the RF model (93.88% vs. 73.47%). Conclusion:Among the machine learning prediction models for cervical cancer and precancerous lesions constructed based on human DNA methylation, the NB model has good predictive performance for CIN2 and above lesions, and may be used for screening of cervical cancer and precancerous lesions.

Objective:Using methylation characteristics of human genes to construct machine learning predictive models for screening cervical cancer and precancerous lesions.Methods:Human DNA methylation detection was performed on 224 cervical exfoliated cell specimens from the Cancer Hospital of the Chinese Academy of Medical Sciences, Tianjin Central Hospital of Gynecology Obstetrics, Xinmi Maternal and Child Health Hospital of Henan Province, West China Second Affiliated Hospital of Sichuan University, and Heping Hospital Affiliated to Changzhi Medical College collected during April 2014 and March 2015. The hypermethylated gene fragments related to cervical cancer were selected by high-density, high-association, and hypermethylated gene fragment screening and the LASSO regression algorithm. Taking cervical intraepithelial neoplasia grade 2 (CIN2) or more severe lesions as the research outcome, machine learning predictive models based on the random forest (RF), naive Bayes (NB), and support vector machine (SVM) algorithm, respectively, were constructed. A total of 144 outpatient specimens were used as the training set and 80 cervical exfoliated cell specimens from women participating in the cervical cancer screening program were used as the test set to verify the predictive models. Using histological diagnosis results as the gold standard, the detection efficacy for CIN2 or more severe lesions of the three machine learning predictive models were compared with that of the human papilloma virus (HPV) detection and cytological diagnosis.Results:In the training set of 144 cases, there were 34 cases of HPV positivity, with a positive rate of 23.61%. Cytologically, there were 37 cases diagnosed as no intraepithelial lesion or malignancy (NILM), and 107 cases diagnosed as atypical squamous cells of undetermined significance (ASC-US) or above. Histologically, there were 28 cases without cervical intraepithelial neoplasia or benign cervical lesions, 31 cases of CIN1, 18 cases of CIN2, 31 cases of CIN3, and 36 cases of squamous cell carcinoma. Seven hypermethylated gene fragments were selected from 45 genes, and three machine learning prediction models based on the RF, NB, and SVM algorithm, respectively, were constructed. In the validation set of 80 cases, there were 28 cases of HPV positivity, with a positive rate of 35.00%. Cytologically, there were 65 cases diagnosed as NILM and 15 cases as ASC-US or above. Histologically, there were 39 cases without cervical intraepithelial neoplasia or benign cervical lesions, 10 cases of CIN1, 10 cases of CIN2, 11 cases of CIN3, and 10 cases of squamous cell carcinoma. In the validation set, the area under the curve (AUC) values of the RF model, NB model, SVM model, HPV detection, and cytological diagnosis of CIN2 or above were 0.90, 0.88, 0.82, 0.68, and 0.45, respectively. The DeLong test showed that there was no statistically significant difference in the AUC values between the RF, NB, and SVM models (all P＞0.05), and the AUC values of the RF and NB models were higher than that of HPV detection (both P＜0.01), and the AUC values of the RF, NB, and SVM models were higher than that of cytological diagnosis (all P＜0.01). Compared with the NB model, the sensitivity of the RF model was similar (80.65% vs. 77.42%), but the specificity of the NB model was much higher than that of the RF model (93.88% vs. 73.47%). Conclusion:Among the machine learning prediction models for cervical cancer and precancerous lesions constructed based on human DNA methylation, the NB model has good predictive performance for CIN2 and above lesions, and may be used for screening of cervical cancer and precancerous lesions.

Objective:To explore the impact of early and late antibody-mediated rejection (AMR) on treatment options and allograft outcomes after kidney transplantation (KT).Methods:From January 2013 to December 2022, the study retrospectively enrolled 141 KT allograft recipients receiving allograft biopsy and diagnosed as AMR according to the Banff 2019 criteria. Recipients with a diagnosis of AMR within 30 days post-KT were classified into early AMR group (n=19) while the remainders assigned as late AMR group (n=122). The outcome endpoints included recipient survival rate, death-censored graft survival rate, follow-up estimated glomerular filtration rate (eGFR) and immunodominant donor-specific antibody (DSA) intensity. Wilcoxon's test was utilized for assessing the differences in eGFR and DSA intensity while Kaplan-Meier curve and Log-rank test were employed for evaluating graft survival impact. Treatment regimens for AMR were collected and categorized.Results:The median follow-up duration was 2.6(1.2, 5.2) year. No graft failure was noted in early AMR group while 44 recipients in late AMR group experienced graft failure, with 34 cases (77.2%) due to AMR progression. The 5-year death-censored graft survival rate was significantly better in early AMR group than that in late AMR group [100% vs 60.1%(50.5%, 71.6%), P=0.002]. The one-year change in eGFR for early AMR group was significantly superior to that of late AMR group [19.3(-2.6, 38.1) vs -3.3(-14.0, 5.4), P=0.001]. One-year mean fluorescent intensity (MFI) of early AMR group was 1 158(401.5, 3 126.5). It was significantly lower than that when diagnosed with early AMR [3 120.5(2 392.8, 9 340.0)] and one-year MFI of late AMR group [8 094(2 251.5, 13 560.5)] ( P=0.005, P<0.001). Early AMR group primarily received standard treatment (3/19, 15.8%) and regimens centered on rituximab and/or bortezomib (7/19, 43.8%). Late AMR group mainly received standard (16/122, 13.1%) or intensified regimens (9/122, 7.4%) and regimens focused upon rituximab and/or bortezomib (32/122, 26.2%) and MP monotherapy (21/122, 17.2%). Conclusion:The outcome for early AMR is significantly better than that for late AMR. For early AMR, early and robust immunosuppression is recommended. For late AMR, early detection and timely treatment are crucial and individualized strategies should be implemented.

Objective: To examine the association between serum vitamin D level and thyroid function indicators among elderly patients with type 2 diabetes mellitus (T2DM), so as to provide the evidence for the prevention and treatment of thyroid function abnormality among elderly patients with T2DM. Methods: Inpatients aged 60 years and older and admitted to the department of endocrinology of Zhejiang Hospital were selected as the study subjects. Gender, age, course of disease and other basic information were collected through questionnaire surveys. The serum 25-hydroxyvitamin D[25-(OH) D], thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), total triiodothyronine (TT3), and total thyroxine (TT4) were measured. The correlation between serum vitamin D level and thyroid function indicators in elderly patients with T2DM was evaluated by a multiple linear regression model. Results: A total of 402 elderly patients with T2DM were surveyed, including 210 males (52.24%) and 192 females (47.76%), and had a median age of 70.00 (interquartile range, 12.00) years and a median course of disease of 14.00 (interquartile range, 14.00) years. There were 162 patients with insufficiency of vitamin D (40.30%) and 182 patients with deficiency (45.27%). The levels of TSH and glycated hemoglobin in the vitamin D deficiency group were (2.34±1.66) μIU/mL and (8.83±2.14) %, respectively, which were higher than those in the normal group [(1.74±1.10) μIU/mL and (8.11±1.75) %; P<0.05]. The levels of FT3 and FT3/FT4 in the vitamin D deficiency group were (2.86±0.48) μIU/mL and 2.85±0.71, respectively, which were lower than those in the vitamin D insufficiency group [(3.09±0.47) pg/mL and 3.14±0.81, P<0.05]. Multiple linear regression analysis showed a negative correlation between 25- (OH) D and TSH (β'=-0.159, P=0.001). Conclusion The vitamin D deficiency may be associated with the increase of TSH level among the elderly patients with T2DM.

ObjectiveTo analyze the incidence， recovery rate and associated factors of nonalcoholic fatty liver disease （NAFLD） among residents aged 65 years old and above in Xinqiao Community of Songjiang， Shanghai， and to provide basic data for further efficient community management. MethodsData of annual geriatric physical examination program for residents aged 65 and above were collected in Xinqiao Community， Songjiang from 2016 to 2022. Those residents who participated twice or more were included in this analysis. Data were collated into longitudinal form. For each participant， data of the first physical examination was used as baseline， and each subsequent examination was taken as follow-up. Incidence and recovery rate of NAFLD were calculated. Cox proportional hazard models were used to explore the associated factors and their changes with the onset and recovery of NAFLD. ResultsDuring the study period， a total of 11 983 residents participated in physical examinations， of which 8 644 participated twice or more， and 8 154 had no history of excessive alcohol consumption. B-ultrasound showed that there were 5 267 residents without NAFLD and 2 887 with NAFLD at baseline. After a median follow-up of 3.3 years， the incidence density of NAFLD in this population was estimated to be 11.5 per 100 person-years， and the recovery density was 23.4 per 100 person-years. The incidence density of NAFLD was negatively associated with age， and positively associated with baseline BMI， abdominal obesity， high fasting blood glucose， and high triglycerides. The recovery density was negatively associated with baseline BMI and abdominal obesity. Compared with those with normal BMI at both baseline and follow-up， those with persistent obesity showed the highest risk of NAFLD （males： HR： 3.19， 95%CI： 2.16-4.70； females： HR： 3.34， 95%CI： 2.46-4.54） and the lowest potential of recovery （males： HR： 0.58， 95%CI： 0.42-0.82； females： HR： 0.58， 95%CI： 0.44-0.77）. Persistently high triglycerides were also associated with a higher risk of developing the disease. ConclusionResidents aged 65 years old and above in Xinqiao， Shanghai had a higher incidence and recovery rate of NAFLD. Women， being obese and having hyperlipidemia are at a higher risk for the development and persistence of NAFLD.

Objective:To investigate the prevalence and mortality of dementia and assess the impact of geriatric syndromes (GS) on the risk for dementia and death in elderly population in Beijing.Methods:A cross-sectional survey was conducted in the elderly population aged ≥65 years and selected by a multi-stage sampling in Beijing during 2013-2015. Cognitive function was screened using the Chinese Revised Version of the Mini-Mental State Examination (MMSE). Then, neurological examination and psychiatric assessment were performed for those with the MMSE score lower than the cut-off value. The information about GS prevalence was also collected. The study also collected death records for all individuals from baseline until December 31, 2019. Based on the age and gender distribution from Beijing data of the 2010 Six th National Population Census, the dementia prevalence in the study population was directly standardized. Logistic regression analysis was used to evaluate the association of different forms of dementia with GS, and Cox proportional hazards regression model was used to estimate the hazard ratio ( HR) and 95% CI of death. Results:During 2013-2015, a total of 2 935 individuals completed dementia assessments, of which 167 were diagnosed with dementia. The standardized prevalence of dementia was 5.9% (95% CI: 5.0%-17.4%). The individuals with Alzheimer's disease (AD) and vascular dementia (VaD) accounted for 58.7% and 28.1% of total individuals with dementia, respectively. Aging, lower education level, urinary incontinence, and fall were risk factors for AD, while disability of activity of daily life dependence, hypertension, and stroke were found to be risk factors for VaD. After a median follow-up of 5.44 person-years, 399 deaths were recorded. The 5-year mortality risk was 2.87 (95% CI: 1.92-4.17) times and 4.93 (95% CI: 3.23-7.53) times higher for the elderly individuals with AD and VaD, respectively, compared to non-demented individuals. After adjusting for demographic, GS, and cardiovascular risk factors, the mortality risk in the elderly individuals with AD showed no significant difference compared with non-demented individuals ( HR=1.32, 95% CI: 0.89-1.97), while the mortality risk in those with VaD was 2.46 (95% CI: 1.49-4.05) times higher than that in non-demented individuals. Conclusions:The prevalence of dementia in Beijing increased significantly in the context of population aging, especially the prevalence of AD. The presence of GS increased the risks for AD and VaD, as well as the risk for death. Close attention needs to be paid to GS management in dementia prevention in elderly population.

Humans ; Clavicle ; Fractures, Bone/surgery*

OBJECTIVE: To report the clinical and genetic characteristics of a rare case of Gitelman syndrome with comorbid Graves disease and ACTH-independent adrenocortical adenoma. METHODS: A patient who had presented at the Nanchong Central Hospital on December 21, 2020 was selected as the study subject. Clinical data of the patient was collected. Whole-exome sequencing was carried out on DNA extracted from peripheral venous blood samples from the patient and her family members. RESULTS: The patient, a 45-year-old woman, was found to have Graves disease, ACTH-independent Cushing syndrome, hypokalemia and hypomagnesemia following the discovery of an adrenal incidentaloma. MRI scan had revealed a 3.8 cm × 3.2 cm mass in the left adrenal gland. The mass was removed by surgery and confirmed as adrenocortical adenoma. DNA sequencing revealed that the patient and her sister have both harbored compound heterozygous variants of the SLC12A3 gene, namely c.1444-10(IVS11)G>A and c.179(exon1)C>T (p.T60M), which were respectively inherited from their father and mother. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.1444-10(IVS11)G>A and c.179(exon1)C>T (p.T60M) were respectively classified as a variant of uncertain significance (PM2_Supporting+PP3) and a likely pathogenic variant (PM3_Strong+PM1+PP3). CONCLUSION The conjunction of Gitelman syndrome with Graves disease and adrenal cortex adenoma is rather rare. The newly discovered c.1444-10(IVS11)G>A variant of the SLC12A3 gene, together with the heterozygous variant of c.179(exon1)C>T (p.T60M), probably underlay the pathogenesis in this patient.
Humans ; Female ; Middle Aged ; Gitelman Syndrome/genetics* ; Adrenocortical Adenoma ; Hypokalemia ; Graves Disease/genetics* ; Mothers ; Mutation ; Solute Carrier Family 12, Member 3