Objective To investigate the role of mitochondrial transcription factor A (TFAM) in platinum-resistant ovarian cancer cells and its effects on metabolic reprogramming and sensitivity to platinum-based drugs Methods The mitochondrial function and metabolic characteristics of platinum-resistant ovarian cancer cells were analyzed. A TFAM-overexpressing cell model was established to assess its effects on platinum sensitivity, mitochondrial function, and aerobic glycolysis; and glycolytic enzyme and drug-resistant protein expression were analyzed. Results Platinum-resistant ovarian cancer cells exhibited considerable mitochondrial dysfunction (reduced oxygen consumption rate) and enhanced aerobic glycolysis (increased extracellular acidification rate, glucose uptake, and lactate production). TFAM was downregulated in resistant cells. Meanwhile, TFAM overexpression significantly enhanced platinum sensitivity (P<0.01), restored mitochondrial function, and inhibited aerobic glycolysis. The expression levels of glycolytic enzymes and drug-resistant proteins were also downregulated (P<0.05). Conclusion TFAM downregulation is associated with suppressed oxidative phosphorylation and enhanced aerobic glycolysis in platinum-resistant ovarian cancer cells. TFAM overexpression can restore cellular dependence on oxidative phosphorylation and increase platinum sensitivity, suggesting that TFAM is a potential therapeutic target for reversing platinum resistance.

Objective To investigate the screening results and factors affecting abnormal detection rates among high-risk groups of esophageal cancer and to explore effective intervention measures. Methods We investigated and collected the information on gender, education level, age, marital status, symptoms of reflux esophagitis (heartburn, acid reflux, belching, hiccup, foreign body sensation in the pharynx, and difficulty swallowing), consumption of pickled vegetables, salt use, and esophageal cancer incidence of villagers in a natural village in Wenfeng District, Anyang City, Henan Province. Changes in reflux esophagitis symptoms in the high-incidence area of esophageal cancer before and after 16 years were observed, and the relationship of such changes with esophageal cancer was analyzed. Results In 2008, 711 cases were epidemiologically investigated, including 213 cases with one of the symptoms of reflux esophagitis such as heartburn, acid reflux, belching, hiccups, foreign body sensation in the pharynx, and difficulty swallowing (sorted in accordance with the abovementioned symptoms; if there are multiple symptoms, then the former is taken); 55 cases with at least two related symptoms, among which the most symptom was heartburn in 108 cases (15.1%); followed by acid reflux, belching, etc. In 2024, the same group of people was investigated, and eight people were missing because of relocation. A total of 703 people were successfully investigated, of which 189 cases (26.8%) had one of the symptoms of reflux esophagitis, such as heartburn (sorted in accordance with relevant symptoms, if there are multiple symptoms, then the former will be selected); 167 cases (23.7%) had at least two related symptoms, among which the most symptom was heartburn in 139 cases (19.7%); followed by acid reflux. Over 16 years, among the 703 people investigated, 45 cases had esophageal cancer and they had one or more of the abovementioned symptoms. No significant differences in the reflux esophagitis-like symptoms were found between 2008 and 2024 (P=0.26); no significant differences in the composition of reflux esophagitis-like symptoms were found between 2008 and 2024 (P=0.299). Conclusion The detection rate of reflux esophagitis-related symptoms in the population in a high-risk area of esophageal cancer has not decreased in the past 16 years, and the high-risk factors still exist. Esophageal cancer is closely related to reflux esophagitis, and clinical practice can provide early diagnosis and treatment for high-risk population.

Objective To investigatethe relationship between gastroesophageal reflux disease (GERD) symptoms and clinicopathological characteristics, p53 expression, and survival of Chinese patients with esophageal adenocarcinoma. Methods A total of 3882 patients with esophageal adenocarcinoma, 970 matched patients with esophageal squamous cell carcinoma, and 970 matched patients with gastric cardia adenocarcinoma were included to compare the incidence of GERD symptoms. Patients with esophageal adenocarcinoma were divided into two groups according to the presence and absence of GERD symptoms. The differences in clinicopathological characteristics and p53 expression between the two groups were compared by chi-square test, and the differences in survival between the two groups were compared by landmark analysis. Results The incidence of GERD symptoms increased successively in esophageal squamous cell carcinoma, esophageal adenocarcinoma, and gastric cardia adenocarcinoma. In patients with esophageal adenocarcinoma, the proportions of male, less than 65 years old, lower thoracic tumors, tumors without squamous cell carcinoma, poorly differentiation, early tumors (stage 0-I), and p53-positive tumors in the group with GERD symptoms were higher than those in the group without GERD symptoms; moreover, the long-term survival (≥15 years) was better. Conclusion GERD symptom is an important clinical sign of esophageal adenocarcinoma. It is closely related to specific clinicopathological characteristics, p53 overexpression, and good long-term prognosis.

Objective To analyze the differences in clinical indicators between malignant insulinoma and benign in-sulinoma,in order to provide diagnostic and therapeutic insights for the early detection and diagnosis of malignant insulinoma.Methods A retrospective analysis was conducted in patients diagnosed and treated for insulinoma at Peking Union Medical College Hospital from January 2018 to June 2022.Among them,10 cases were diagnosed as malignant insulinoma.Twenty cases of benign insulinoma patients matched for age,sex,and body mass index(BMI),were randomly selected.Statistical analysis was performed to compare the differences between malignant and benign insulinomas.Results 1)Compared to benign insulinoma,malignant insulinoma showed significantly ele-vated C-peptide(CP)and C-peptide to glucose ratio(CPGlu)during hypoglycemia(blood glucose＜3.0 mmol/L)[6.04(3.40,6.76)vs 1.68(1.39,2.47)ng/mL,P＜0.05),2.25(1.12,3.58)vs 0.74(0.54,1.54),P＜0.05].The tumor diameter(DIA)was larger(1.9±0.6 vs 1.4±0.3 cm,P＜0.05),and the insulin level at 300 minutes(INS300)during the 5-hour oral glucose tolerance test(5 h OGTT)was significantly elevated(30.47±5.67 vs 9.67±3.32)μIU/mL,P＜0.01).Levels of blood tumor markers AFP,CEA,and CA724 were also increased(P＜0.05).2)Correlation analysis indicated that CP,CPGlu,DIA,INS300,AFP,CEA,and CA724 were positively correlated with malignant insulinoma during hypoglycemia.3)The ROC curve analysis suggested that the optimal cut-off points for distinguishing malignant from benign insulinomas were CP 2.49 ng/mL,CPGlu 1.31,DIA 1.85 cm,and INS300 20.22 μIU/mL,respectively.Conclusions In clinical practice,if an insulinoma patient has a CP level higher than 2.49 ng/mL and a tumor diameter larger than 1.9 cm during hypoglycemia,the possibility of malignant insulinoma should be considered,warranting further examinations and enhanced follow-up.Persistent elevation of AFP,CEA,and CA724 may indicate malignant insulinoma.

Objective : To identify possible associated genetic variants and characterise the clinical presentation of isolated ectopia lentis (IEL) . Methods : Forty - eight members with 5 generations of an IEL family were enrolled in this study. Peripheral blood samples of all members were collected , and clinical manifestations were observed through physical examination and routine ophthalmological examination. Whole⁃exome sequencing (WES) was performed for two patients to identify disease⁃causing variants. The target variants were verified by Sanger sequencing in family members and 200 normal controls. Then , candidate variants were verified using Sanger sequencing in family members and 200 healthy controls. SIFT , PolyPhen and MutationTester were used to predict the protein function. Results : A total of 13 IEL patients in this family which inherited in an autosomal dominant pattern. The mean age at disease onset was 51. 5 years. The main clinical phenotype of this ICE was characterised by ectopia lentis which anterior inclinated to the anterior chamber. As the anterior chamber became shallow , and the angle of the chamber became narrow , and eventually resulted in the secondary glaucoma. A heterozygous missense variantin the fibrillin gene⁃1 (FBN1) gene (c. 3463G > A) was identified by WES , which was present in all patients but was absent in 200 healthy controls. SIFT , PolyPhen and MutationTester predicted that the variant affected protein function. Conclusion This IEL family is characterized by secondary glaucoma as the first symptom which is caused by ectopia lens with inclination. The c. 3463G > A of FBN1 gene may be the pathogenic mutation leading to IEL in this family.

Objective: To investigate the prevalence of frailty and its influencing factors among the elderly, so as to provide the evidence for prevention and control of frailty. Methods: The elderly population at ages of 65 years and older were selected from 14 administrative villages or communities in Wuzhong District, Suzhou City, Jiangsu Province, using the random cluster sample method from July to November, 2022. Demographic information, smoking and alcohol consumption were collected through questionnaire surveys. Physical activity, sleep quality and frailty were evaluated using the International Physical Activity Questionnaire-Short, Pittsburgh Sleep Quality Index and the FRAIL Scale, respectively. Factors affecting frailty among the elderly were evaluated using a multinomial logistic regression model. Results: A total of 8 782 elderly peolple were surveyed, including 4 259 males (48.50%) and 4 523 females (51.50%). The median age was 71.00 (interquartile range, 8.00) years. There were 2 145 cases with pre-frailty (24.42%) and 189 cases with frailty (2.15%). Multinomial logistic regression analysis showed that age (75-<85 years, OR=1.330, 95%CI: 1.186-1.492; ≥85 years, OR=2.452, 95%CI: 1.882-3.195), smoking (current smoking, OR=0.838, 95%CI: 0.714-0.983), physical activity level (low, OR=1.161, 95%CI: 1.010-1.333) and sleep quality (poor, OR=2.248, 95%CI: 1.822-2.774) were associated with pre-frailty; age (75-<85 years,OR=2.629, 95%CI: 1.921-3.596; ≥85 years, OR=3.067, 95%CI: 1.621-5.801), educational level (junior high school and above, OR=0.488, 95%CI: 0.298-0.798), body mass index (underweight, OR=1.848, 95%CI: 1.023-3.337; obesity, OR=1.798, 95%CI: 1.180-2.740), smoking (quit smoking, OR=1.787, 95%CI: 1.007-3.171; current smoking, OR=0.448, 95%CI: 0.242-0.830), alcohol consumption (yes, OR=0.532, 95%CI: 0.291-0.972), physical activity level (low, OR=2.757, 95%CI: 1.646-4.616) and sleep quality (poor, OR=3.911, 95%CI: 2.438-6.273) were associated with frailty. Conclusion Older, low physical activity level, poor sleep quality, underweight and obesity are associated with frailty of the elderly.

Objective To identify possible associated genetic variants and characterise the clinical presentation of isolated ectopia lentis (IEL).Methods Forty-eight members with 5 generations of an IEL family were enrolled in this study.Peripheral blood samples of all members were collected, and clinical manifestations were observed through physical examination and routine ophthalmological examination.Whole-exome sequencing (WES) was per-formed for two patients to identify disease-causing variants.The target variants were verified by Sanger sequencing in family members and 200 normal controls.Then, candidate variants were verified using Sanger sequencing in family members and 200 healthy controls.SIFT, PolyPhen and MutationTester were used to predict the protein function.Results A total of 13 IEL patients in this family which inherited in an autosomal dominant pattern.The mean age at disease onset was 51.5 years.The main clinical phenotype of this ICE was characterised by ectopia lentis which anterior inclinated to the anterior chamber.As the anterior chamber became shallow, and the angle of the chamber became narrow, and eventually resulted in the secondary glaucoma.A heterozygous missense variant in the fibrillin gene-1 (FBN1) gene (c.3463G>A) was identified by WES, which was present in all patients but was absent in 200 healthy controls.SIFT, PolyPhen and MutationTester predicted that the variant affected protein function.Conclusion This IEL family is characterized by secondary glaucoma as the first symptom which is caused by ectopia lens with inclination.The c.3463G>A of FBN1 gene may be the pathogenic mutation leading to IEL in this family.

Objective To identify possible associated genetic variants and characterise the clinical presentation of isolated ectopia lentis (IEL).Methods Forty-eight members with 5 generations of an IEL family were enrolled in this study.Peripheral blood samples of all members were collected, and clinical manifestations were observed through physical examination and routine ophthalmological examination.Whole-exome sequencing (WES) was per-formed for two patients to identify disease-causing variants.The target variants were verified by Sanger sequencing in family members and 200 normal controls.Then, candidate variants were verified using Sanger sequencing in family members and 200 healthy controls.SIFT, PolyPhen and MutationTester were used to predict the protein function.Results A total of 13 IEL patients in this family which inherited in an autosomal dominant pattern.The mean age at disease onset was 51.5 years.The main clinical phenotype of this ICE was characterised by ectopia lentis which anterior inclinated to the anterior chamber.As the anterior chamber became shallow, and the angle of the chamber became narrow, and eventually resulted in the secondary glaucoma.A heterozygous missense variant in the fibrillin gene-1 (FBN1) gene (c.3463G>A) was identified by WES, which was present in all patients but was absent in 200 healthy controls.SIFT, PolyPhen and MutationTester predicted that the variant affected protein function.Conclusion This IEL family is characterized by secondary glaucoma as the first symptom which is caused by ectopia lens with inclination.The c.3463G>A of FBN1 gene may be the pathogenic mutation leading to IEL in this family.

Objective To identify possible associated genetic variants and characterise the clinical presentation of isolated ectopia lentis (IEL).Methods Forty-eight members with 5 generations of an IEL family were enrolled in this study.Peripheral blood samples of all members were collected, and clinical manifestations were observed through physical examination and routine ophthalmological examination.Whole-exome sequencing (WES) was per-formed for two patients to identify disease-causing variants.The target variants were verified by Sanger sequencing in family members and 200 normal controls.Then, candidate variants were verified using Sanger sequencing in family members and 200 healthy controls.SIFT, PolyPhen and MutationTester were used to predict the protein function.Results A total of 13 IEL patients in this family which inherited in an autosomal dominant pattern.The mean age at disease onset was 51.5 years.The main clinical phenotype of this ICE was characterised by ectopia lentis which anterior inclinated to the anterior chamber.As the anterior chamber became shallow, and the angle of the chamber became narrow, and eventually resulted in the secondary glaucoma.A heterozygous missense variant in the fibrillin gene-1 (FBN1) gene (c.3463G>A) was identified by WES, which was present in all patients but was absent in 200 healthy controls.SIFT, PolyPhen and MutationTester predicted that the variant affected protein function.Conclusion This IEL family is characterized by secondary glaucoma as the first symptom which is caused by ectopia lens with inclination.The c.3463G>A of FBN1 gene may be the pathogenic mutation leading to IEL in this family.

Objective To identify possible associated genetic variants and characterise the clinical presentation of isolated ectopia lentis (IEL).Methods Forty-eight members with 5 generations of an IEL family were enrolled in this study.Peripheral blood samples of all members were collected, and clinical manifestations were observed through physical examination and routine ophthalmological examination.Whole-exome sequencing (WES) was per-formed for two patients to identify disease-causing variants.The target variants were verified by Sanger sequencing in family members and 200 normal controls.Then, candidate variants were verified using Sanger sequencing in family members and 200 healthy controls.SIFT, PolyPhen and MutationTester were used to predict the protein function.Results A total of 13 IEL patients in this family which inherited in an autosomal dominant pattern.The mean age at disease onset was 51.5 years.The main clinical phenotype of this ICE was characterised by ectopia lentis which anterior inclinated to the anterior chamber.As the anterior chamber became shallow, and the angle of the chamber became narrow, and eventually resulted in the secondary glaucoma.A heterozygous missense variant in the fibrillin gene-1 (FBN1) gene (c.3463G>A) was identified by WES, which was present in all patients but was absent in 200 healthy controls.SIFT, PolyPhen and MutationTester predicted that the variant affected protein function.Conclusion This IEL family is characterized by secondary glaucoma as the first symptom which is caused by ectopia lens with inclination.The c.3463G>A of FBN1 gene may be the pathogenic mutation leading to IEL in this family.