OBJECTIVES: To investigate the molecular epidemiology of children with phenylketonuria (PKU) in Gansu, China, providing foundational data for intervention strategies. METHODS: A retrospective analysis was conducted on 1 159 PKU families who attended Gansu Provincial Maternity and Child Care Hospital from January 2012 to December 2024. Sanger sequencing, multiplex ligation-dependent probe amplification, whole exome sequencing, and deep intronic variant analysis were used to analyze the PAH gene. RESULTS: For the 1 159 children with PKU, 2 295 variants were identified in 2 318 alleles, resulting in a detection rate of 99.01%. The detection rates were 100% (914/914) in 457 classic PKU families, 99.45% (907/912) in 456 mild PKU families, and 96.34% (474/492) in 246 mild hyperphenylalaninemia families. The 2 295 variants detected comprised 208 distinct mutation types, among which c.728G>A (14.95%, 343/2 295) had the highest frequency, followed by c.611A>G (4.88%, 112/2 295) and c.721C>T (4.79%, 110/2 295). The cumulative frequency of the top 23 hotspot variants reached 70.28% (1 613/2 295), and most variant alleles were detected in exon 7 (29.19%, 670/2 295). CONCLUSIONS Deep intronic variant analysis of the PAH gene can improve the genetic diagnostic rate of PKU. The development of targeted detection kits for PAH hotspot variants may enable precision screening programs and enhance preventive strategies for PKU.
Humans ; Phenylketonurias/epidemiology* ; Female ; Male ; Retrospective Studies ; Phenylalanine Hydroxylase/genetics* ; Mutation ; Child, Preschool ; China/epidemiology* ; Child ; Infant

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

In recent years,the market share of food and medicine homology substances has continued to grow,and various types of contamination issues have become the focus of attention both inside and outside the industry.The contamination not only affects the original medicinal quality,but also leads to the accumulation of toxic substances in the human body,causing acute and chronic severe hazards such as vomiting,poisoning and cancer.Therefore,the development of biosensors that can conveniently,accurately and sensitively detect various pollutants in food and medicine homology substances has become a research hotspot.Aptasensors based on metal-organic frameworks(MOFs)with advantages such as strong specificity,rapid response and simple operation,have been widely used in detection of various pollutants.This review focused on the research progress of aptasensors based on MOFs for detection of food and medicine homology contamination in the past few years,and provided a detailed comparison and analysis for detection of chemical pollutants(such as pesticide residues,heavy metal residues,mycotoxins,etc.)and microbial contamination in food and medicine homology substances.Besides,the development trend and possible challenges of MOFs aptasensors in detection of food and medicine homology substances in the future were discussed,which was anticipated to provide a reference for the development of new MOFs aptasensors.

Objective:To explore the effect of Lactobacillus reuteri on testicular injury in mice exposed to neonicotinoid insec-ticides(NNI).Methods:Fifteen C57BL/6 male mice were randomly divided into control group(CTRI.group),exposure group(NNI group)and Lactobacillus intervention group(NNI-L group).The mice in CTRL group were given 0.02ml/g of 0.5％carboxym-ethyl cellulose sodium solution by gavage for 14 days.The mice in NNI group were given 0.02 ml/g of NNI mixture by gavage for 14 days.The mice in NNI-L group were given 0.02 ml/g of NNI mixture by gavage and 5 × 108cfu/ml of Lactobacillus reuteri powder so-lution for 14 days.Then,the histomorphology and function of testicle were evaluated by hematoxylin-eosin staining,immunofluores-cence staining and RNA sequencing.Results:Compared with CTRL group,the thickness of testicular seminiferous epithelium in the NNI group was significantly thinner.And the decline in the number of spermatogenic cells and sperm was observed.And the expression of spermatogonial stem cell marker UCHL1 was down-regulated which was significantly improved in NNI-L group compared with the NNI group.The abnormal expressions of hormone and sperm methylation related genes in testis of NNI group were detected by RNA sequen-cing,with significant down-regulation being found in NPFF and IGF2.While the expression of HSD3B8 was significantly up-regulated.The abnormal expression of these genes could be significantly improved after oral administration of Lactobacillus reuteri.Conclusion:Testicular spermatogenesis and endocrine function can be damaged by NNI exposure.And oral administration of Lactoba-cillus reuteri protects testis from the adverse effects of NNI toxicity.

Objective To develop and validate a nomogram model for predicting recurrence after radiofre-quency catheter ablation(RFCA)in patients with atrial fibrillation and heart failure using body surface electrocar-diogram indicators and clinical indicators.Methods We retrospectively analyzed 305 patients with atrial fibrilla-tion complicated with heart failure who underwent RFCA from January 2019 to January 2024.Patients were random-ized into training set(213 cases)and validation set(92 cases)at a ratio of 7:3 and followed up for at least 1 year.Based on the recurrence status,the patients were divided into recurrence group and non-recurrence group,with body surface electrocardiogram indicators and clinical indicators collected.Multivariate logistic regression analysis identified for risk factors for post RFCA recurrence,which were used to construct a nomogram.Model performance was assessed using the area under the receiver operating characteristic curve(AUC),Hosmer-Lemeshow test,calibration curves,and decision curve analysis(DCA).Results Among the 305 patients,84(27.54％)experi-enced recurrence after treatment.In the training set,61 patients had recurrence and 152 did not.No statistical differences were observed between the training set and the validation set(all P>0.05).In the training set,the recurrence group exhibited a higher proportion of persistent atrial fibrillation and significantly higher CHA2DS2-VASc scores,larger left atrial diameter,longer PR interval,and higher levels of NLR and NT-proBNP compared to the non-recurrence group(all P<0.05).Multivariate stepwise regression analysis revealed that high CHA2DS2-VASc score,long left atrial diameter,prolonged PR interval,and high NLR were independent risk factors of recurrence after RFCA(P<0.05)A four-factor prediction model was established as:Ln(P/1-P)=-12.87+0.84*CHA2DS2-VASc score+0.11* left atrial diameter+0.03*PR interval+0.31*NLR.The training and validation models showed AUCs of 0.85(95％CI:0.80～0.91)and 0.85(95％CI:0.76～0.94),respectively,suggesting that the model had good predictive efficiency.Hosmer-Lemeshow test results(χ2=2.43,P=0.965 for the training set;χ2=5.30,P=0.725 for the validation set)confirmed model fit,indicating that the fitted probability value was consistent with the actual probability value.Calibration curves after 1 000 times of Bootstrap repeated sampling showed the bias calibration curves of the training set and the validation set had good consistency with the actual curves,both close to the ideal curve.DCA revealed clinical utility across a wide threshold probability range(0.02～1.0 for the training set;0.04～1.0 for the validation set).Conclusion This nomogram,based on body surface electrocardiogram indicators and clinical indicators,effectively predicts post-RFCA recurrence in atrial fibrillation and heart failure patients,offering a useful tool for early assessment of recurrence risk.

Objective To develop and validate a nomogram model for predicting recurrence after radiofre-quency catheter ablation(RFCA)in patients with atrial fibrillation and heart failure using body surface electrocar-diogram indicators and clinical indicators.Methods We retrospectively analyzed 305 patients with atrial fibrilla-tion complicated with heart failure who underwent RFCA from January 2019 to January 2024.Patients were random-ized into training set(213 cases)and validation set(92 cases)at a ratio of 7:3 and followed up for at least 1 year.Based on the recurrence status,the patients were divided into recurrence group and non-recurrence group,with body surface electrocardiogram indicators and clinical indicators collected.Multivariate logistic regression analysis identified for risk factors for post RFCA recurrence,which were used to construct a nomogram.Model performance was assessed using the area under the receiver operating characteristic curve(AUC),Hosmer-Lemeshow test,calibration curves,and decision curve analysis(DCA).Results Among the 305 patients,84(27.54％)experi-enced recurrence after treatment.In the training set,61 patients had recurrence and 152 did not.No statistical differences were observed between the training set and the validation set(all P>0.05).In the training set,the recurrence group exhibited a higher proportion of persistent atrial fibrillation and significantly higher CHA2DS2-VASc scores,larger left atrial diameter,longer PR interval,and higher levels of NLR and NT-proBNP compared to the non-recurrence group(all P<0.05).Multivariate stepwise regression analysis revealed that high CHA2DS2-VASc score,long left atrial diameter,prolonged PR interval,and high NLR were independent risk factors of recurrence after RFCA(P<0.05)A four-factor prediction model was established as:Ln(P/1-P)=-12.87+0.84*CHA2DS2-VASc score+0.11* left atrial diameter+0.03*PR interval+0.31*NLR.The training and validation models showed AUCs of 0.85(95％CI:0.80～0.91)and 0.85(95％CI:0.76～0.94),respectively,suggesting that the model had good predictive efficiency.Hosmer-Lemeshow test results(χ2=2.43,P=0.965 for the training set;χ2=5.30,P=0.725 for the validation set)confirmed model fit,indicating that the fitted probability value was consistent with the actual probability value.Calibration curves after 1 000 times of Bootstrap repeated sampling showed the bias calibration curves of the training set and the validation set had good consistency with the actual curves,both close to the ideal curve.DCA revealed clinical utility across a wide threshold probability range(0.02～1.0 for the training set;0.04～1.0 for the validation set).Conclusion This nomogram,based on body surface electrocardiogram indicators and clinical indicators,effectively predicts post-RFCA recurrence in atrial fibrillation and heart failure patients,offering a useful tool for early assessment of recurrence risk.

Objective To investigate the effect of individual pretreatment of preoperative medical multi-dimensional carbohydrates on intraoperative body temperature in elderly patients with hip replacement under general anesthesia. Methods A total of 81 elderly patients who underwent unilateral hip replacement in Yancheng Third People's Hospital from January 2022 to June 2024 were selected as the study subjects,and they were randomly divided into the conventional group and the pretreatment group. Both groups of patients were given routine fasting and drinking restriction before operation,and patients in the pretreatment group were given individual pretreatment of 5 mL/kg medical multi-dimensional carbohydrates 2 hours before anesthesia. The perioperative related indicators,body temperature,intraoperative hypothermia,adverse reactions during the recovery period,and pre-anesthesia gastric antral ultrasound examination results of patients in the two groups were compared. Results There was no statistically significant difference in the surgical time or intraoperative intravenous fluid infusion between the two groups (P>0.05). The anesthesia recovery time,tracheal extubation time and intraoperative bleeding volume of patients in the pretreatment group were significantly shorter/less than those in the conventional group (P<0.05). At 30 minutes,60 minutes and the end of the surgery,the body temperature of patients in the pretreatment group was significantly higher than that in the conventional group (P<0.05),and the incidences of intraoperative hypothermia and shivering in the pretreatment group were significantly lower than those in the conventional group (P<0.05). There was no statistically significant difference in the cross-sectional area (CSA) of gastric antrum,gastric volume (GV) or ratio of gastric volume/weight (GV/W) between the two groups of patients (P>0.05). Conclusion The individual pretreatment of 5 mL/kg medical multi-dimensional carbohydrates before surgery can significantly reduce the incidence of intraoperative hypothermia in elderly patients with hip replacement under general anesthesia,promote anesthesia recovery,reduce intraoperative bleeding volume and adverse reactions,and not increase the risk of reflux aspiration.

Objective:To investigate the iodine nutrition level and the prevalence of thyroid nodules in pregnant women in Hubei Province, and to provide a basis for prevention and treatment of iodine deficiency disorders.Methods:According to the requirements of the National Iodine Deficiency Disorders Monitoring Program (2016 Edition), a cross-sectional survey of iodine nutrition status of pregnant women ( n = 321) was conducted from July to October 2020 in two mountainous counties (Tongcheng County and Xingshan County) and two plain counties (Liangzihu District and Xinzhou District) in Hubei Province. Among them, there were 43, 114, and 164 pregnant women in the early, middle, and late stages of pregnancy, respectively. Edible salt samples and once random urine samples were collected to detect salt iodine and urinary iodine, and thyroid ultrasound was performed to calculate the detection rate of thyroid nodules. Results:The coverage rate of iodized salt, qualified rate of iodized salt, and consumption rate of qualified iodized salt in Hubei Province were 99.69% (320/321), 95.94% (307/320) and 95.64% (307/321), respectively. The median urinary iodine level for pregnant women was 164.80 μg/L. Among them, the median urinary iodine levels in Liangzihu District, Tongcheng County, Xinzhou District, and Xingshan County were 175.90, 178.25, 155.80 and 143.00 μg/L, respectively. There was a statistically significant difference in urinary iodine levels among different regions ( H = 8.51, P = 0.037). The median urinary iodine levels of pregnant women in the early, middle, and late stages of pregnancy were 187.20, 144.45, and 172.05 μg/L, respectively. There was no statistically significant difference in urinary iodine levels among pregnant women in different stages of pregnancy ( H = 2.94, P = 0.230). Urinary iodine < 150, 150 - < 250, 250 - < 500, ≥500 μg/L accounted for 45.48% (146/321), 33.33% (107/321), 19.63% (63/321), 1.56% (5/321), respectively. The detection rate of thyroid nodules was 16.82% (54/321), and the goiter rate was 0.93% (3/321). Conclusions:In 2020, Hubei Province is in an appropriate state of iodine, and there are still a considerable proportion of pregnant women in a state of iodine deficiency. The detection rate of thyroid nodules is relatively low. It is necessary to continuously monitor the iodine nutrition of pregnant women, strengthen health promotion on the hazards of iodine deficiency during pregnancy, and minimize maternal and infant health damage caused by iodine deficiency.