Objective:To investigate the screening, clinical and genetic characteristics and prognosis of hereditary tyrosinemia type Ⅰ (HT-Ⅰ) in some areas of Shanghai, and to summarize the relevant characteristics of Chinese cases reported at home and abroad.Methods:From December 2010 to May 2023, the clinical data of children diagnosed with HT-Ⅰ by tandem mass spectrometry combined with genetic detection in Neonatal Screening Center of Shanghai Children′s Hospital were retrospectively analyzed, and the relevant literature was reviewed.Results:A total of 282 149 neonates were screened for genetic metabolic disease by tandem mass spectrometry, and 1 case of HT-Ⅰ was diagnosed, with an incidence of 1∶282 149. Complex heterozygous mutations of FAH genes c. 974C>T and c. 22G>T were found by genetic testing. c. 22G>T was not reported as a new mutation. Diet and drug therapy were given immediately after diagnosis. At present, the follow-up was up to 8 months, and the physical and intellectual development were normal. A total of 32 literatures meeting the inclusion criteria were obtained through database search, and 46 cases of HT-Ⅰ Chinese children were reported. Most of the clinical manifestations were abdominal distension, poor appetite, jaundice, etc., accompanied by different degrees of abnormal coagulation function, hepatosplenomegalysis, cirrhosis and even liver failure. A total of 25 alleles were reported, and the variation of c. 455G>A was the most common. Conclusions:HT-Ⅰ is rare in the population of Shanghai, China, and new mutations enrich the variation spectrum of HT-Ⅰ, which provides basis for family genetic counseling and prenatal diagnosis of children.

Acute carbon monoxide poisoning (ACMP) is a common harmful gas poisoning. Underwent systematic treatment and a 2-3 week pseudo-healing period, some ACMP patients may still develop delayed encephalopathy after acute carbon monoxide poisoning (DEACMP). DEACMP is the most severe complication that could happen to ACMP patients and comes with an exceeding high disability rate. Early identification and adequate intervention measures of DEACMP are particularly crucial for preventing its occurrence in clinical practice. At present, multiple studies have found that after ACMP occurred, a series of biomarkers showed predictive value for detecting the occurrence and development of DEACMP. This paper reviews these biomarkers and their predictive effects on DEACMP, aiming to provide theoretical guidance for the prevention and intervention of DEACMP.

Acute carbon monoxide poisoning (ACMP) is a common harmful gas poisoning. Underwent systematic treatment and a 2-3 week pseudo-healing period, some ACMP patients may still develop delayed encephalopathy after acute carbon monoxide poisoning (DEACMP). DEACMP is the most severe complication that could happen to ACMP patients and comes with an exceeding high disability rate. Early identification and adequate intervention measures of DEACMP are particularly crucial for preventing its occurrence in clinical practice. At present, multiple studies have found that after ACMP occurred, a series of biomarkers showed predictive value for detecting the occurrence and development of DEACMP. This paper reviews these biomarkers and their predictive effects on DEACMP, aiming to provide theoretical guidance for the prevention and intervention of DEACMP.

Objective:To analyze the differences in screening neonatal glucose-6-phosphate dehydrogenase (G6PD) deficiency in different birth seasons, establish screening thresholds for G6PD concentration in each season using indirect methods, and verify the reliability of the results.Methods:This was a cross-sectional study.A total of 140 823 newborns were collected from the Neonatal Screening Center of Shanghai Children′s Hospital from January 2020 to December 2023, including 41 029 cases, 35 796 cases, 33 969 cases and 30 029 cases in spring, summer, autumn and winter groups, respectively.The concentration of G6PD on the dried blood filter paper was determined using an automatic fluorescence analyzer.The distribution and statistical index of concentration values in four seasons were analyzed.The Kolmogorov-Smirnov test was used for normal distribution.The skewed distribution data was converted into approximately normal distribution using Box-Cox.Outliers were eliminated using the interquartile range (Turkey) method.The cumulative frequency distribution map was drawn through R language programming.The linear regression equation Y=B X+ A was fitted.The 0.5th percentile ( P0.5) was used as the screening threshold, which was compared with the reference value given by the manufacturer or laboratory and with the reference change value (RCV). Results:In the spring group, the positive rate was 4.02‰, 91 cases were confirmed, and the incidence was 1∶451.In the summer group, the positive rate was 7.18‰, 90 cases were confirmed, and the incidence was 1∶398.In the autumn group, the positive rate was 3.21‰, 86 cases were confirmed, and the incidence was 1∶395.In the winter group, the positive rate was 2.26‰, 61 cases were confirmed, and the incidence was 1∶492.The incidence rate did not change significantly in the four seasons ( P>0.05).The G6PD concentrations in the four seasons were compared in pairs, and the result was winter>autumn>spring>summer.The thresholds for G6PD screening were established indirectly: 25.08 U/dL, 22.83 U/dL, 26.63 U/dL and 38.01 U/dL in spring, summer, autumn and winter groups, respectively.The relative deviation in the threshold between the summer group and the laboratory was lower than RCV, while that between the other groups was higher than RCV.According to the screening threshold, the negative and positive conformity rates of 12 batches of 120 samples in the inter-laboratory evaluation program of Chinese Taiwan Preventive Medicine Foundation of China reached 100%. Conclusions:There is no difference in the incidence of G6PD deficiency between birth seasons.It is feasible to establish the screening threshold in each season using indirect methods, which is conducive to improving the efficiency of screening.

Objective:To analyze the differences in screening neonatal glucose-6-phosphate dehydrogenase (G6PD) deficiency in different birth seasons, establish screening thresholds for G6PD concentration in each season using indirect methods, and verify the reliability of the results.Methods:This was a cross-sectional study.A total of 140 823 newborns were collected from the Neonatal Screening Center of Shanghai Children′s Hospital from January 2020 to December 2023, including 41 029 cases, 35 796 cases, 33 969 cases and 30 029 cases in spring, summer, autumn and winter groups, respectively.The concentration of G6PD on the dried blood filter paper was determined using an automatic fluorescence analyzer.The distribution and statistical index of concentration values in four seasons were analyzed.The Kolmogorov-Smirnov test was used for normal distribution.The skewed distribution data was converted into approximately normal distribution using Box-Cox.Outliers were eliminated using the interquartile range (Turkey) method.The cumulative frequency distribution map was drawn through R language programming.The linear regression equation Y=B X+ A was fitted.The 0.5th percentile ( P0.5) was used as the screening threshold, which was compared with the reference value given by the manufacturer or laboratory and with the reference change value (RCV). Results:In the spring group, the positive rate was 4.02‰, 91 cases were confirmed, and the incidence was 1∶451.In the summer group, the positive rate was 7.18‰, 90 cases were confirmed, and the incidence was 1∶398.In the autumn group, the positive rate was 3.21‰, 86 cases were confirmed, and the incidence was 1∶395.In the winter group, the positive rate was 2.26‰, 61 cases were confirmed, and the incidence was 1∶492.The incidence rate did not change significantly in the four seasons ( P>0.05).The G6PD concentrations in the four seasons were compared in pairs, and the result was winter>autumn>spring>summer.The thresholds for G6PD screening were established indirectly: 25.08 U/dL, 22.83 U/dL, 26.63 U/dL and 38.01 U/dL in spring, summer, autumn and winter groups, respectively.The relative deviation in the threshold between the summer group and the laboratory was lower than RCV, while that between the other groups was higher than RCV.According to the screening threshold, the negative and positive conformity rates of 12 batches of 120 samples in the inter-laboratory evaluation program of Chinese Taiwan Preventive Medicine Foundation of China reached 100%. Conclusions:There is no difference in the incidence of G6PD deficiency between birth seasons.It is feasible to establish the screening threshold in each season using indirect methods, which is conducive to improving the efficiency of screening.

Objective:To investigate the screening, clinical and genetic characteristics and prognosis of hereditary tyrosinemia type Ⅰ (HT-Ⅰ) in some areas of Shanghai, and to summarize the relevant characteristics of Chinese cases reported at home and abroad.Methods:From December 2010 to May 2023, the clinical data of children diagnosed with HT-Ⅰ by tandem mass spectrometry combined with genetic detection in Neonatal Screening Center of Shanghai Children′s Hospital were retrospectively analyzed, and the relevant literature was reviewed.Results:A total of 282 149 neonates were screened for genetic metabolic disease by tandem mass spectrometry, and 1 case of HT-Ⅰ was diagnosed, with an incidence of 1∶282 149. Complex heterozygous mutations of FAH genes c. 974C>T and c. 22G>T were found by genetic testing. c. 22G>T was not reported as a new mutation. Diet and drug therapy were given immediately after diagnosis. At present, the follow-up was up to 8 months, and the physical and intellectual development were normal. A total of 32 literatures meeting the inclusion criteria were obtained through database search, and 46 cases of HT-Ⅰ Chinese children were reported. Most of the clinical manifestations were abdominal distension, poor appetite, jaundice, etc., accompanied by different degrees of abnormal coagulation function, hepatosplenomegalysis, cirrhosis and even liver failure. A total of 25 alleles were reported, and the variation of c. 455G>A was the most common. Conclusions:HT-Ⅰ is rare in the population of Shanghai, China, and new mutations enrich the variation spectrum of HT-Ⅰ, which provides basis for family genetic counseling and prenatal diagnosis of children.

Objective:To investigate the prognosis and the factors that influence it in patients with non-gastric gastrointestinal stromal tumors (GISTs) who are at low risk of recurrence.Methods:This was a retrospective cohort study. Clinicopathologic and prognostic data from patients with non-gastric GISTs and at low risk of recurrence (i.e., very low-risk or low-risk according to the 2008 version of the Modified NIH Risk Classification), who attended 18 medical centers in China between January 2000 and June 2023, were collected. We excluded patients with a history of prior malignancy, concurrent primary malignancy, multiple GISTs, and those who had received preoperative imatinib. The study cohort comprised 1,571 patients with GISTs, 370 (23.6%) of whom were at very low-risk and 1,201 (76.4%) at low-risk of recurrence. The cohort included 799 (50.9%) men and 772 (49.1%) women of median age 57 (16–93) years. Patients were followed up to July 2024. The prognosis and its influencing factors were analyzed. Receiver operating characteristic curves for tumor diameter and Ki67 were established, and the sensitivity, specificity, area under the curve (AUC) and optimal cut-off value with 95% confidence intervals were calculated. Propensity score matching was implemented using the 1:1 nearest neighbor matching method with a matching tolerance of 0.02.Results:With a median follow-up of 63 (12–267) months, the 5- and 10-year overall survival (OS) rates of the 1,571 patients were 99.5% and 98.0%, respectively, and the 5- and 10-year disease-free survival (DFS) rates were 96.3% and 94.4%, respectively. During postoperative follow-up, 3.8% (60/1,571) patients had disease recurrence or metastasis, comprising 0.8% (3/370) in the very low-risk group and 4.7% (57/1,201) in the low-risk group. In the low-risk group, recurrence or metastasis occurred in 5.5% (25/457) of patients with duodenal GISTs, 3.9% (25/645) of those with small intestinal GISTs, 9.2% (6/65) of those with rectal GISTs, and 10.0% (1/10) of those with colonic GISTs. Among the 60 patients with metastases, 56.7% (34/60) of the metastases were located in the abdominal cavity, 53.3% (32/60) in the liver, and 3.3% (2/60) in bone. During the follow-up period, 13 patients (0.8%) died of disease. Receiver operating characteristic curves were plotted for tumor diameter and Ki67 and assessed using the Jordon index. This showed that the difference in DFS between the two groups was statistically significant when the cutoff value for tumor diameter was 3.5 cm (AUC 0.731, 95% CI: 0.670–0.793, sensitivity 77.7%, specificity 64.1%). Furthermore, the difference in DFS between the two groups was statistically significant when the cutoff value for Ki67 was 5% (AUC 0.693, 95% CI: 0.624–0.762, sensitivity 60.7%, specificity 65.3%). Multifactorial analysis revealed that tumor diameter ≥3.5 cm, Ki67 ≥5%, and R1 resection were independent risk factors for DFS in patients with non-gastric GISTs at low risk of recurrence (all P<0.05). Furthermore, age >57 years, Ki67 ≥5%, and R1 resection were also independent risk factors for OS in patients with non-gastric GISTs at low risk of recurrence (all P<0.05). We also grouped the patients according to whether they had received postoperative adjuvant treatment with imatinib for 1 or 3 years. This yielded 137 patients in the less than 1-year group, 139 in the 1-year plus group; and 44 in both the less than 3 years and 3-years plus group. After propensity score matching for age, tumor diameter, Ki67, and resection status, the differences in survival between the two groups were not statistically significant (all P>0.05). The 10-year DFS and OS were 87.5% and 95.5%, respectively, in the group treated with imatinib for less than 1 year and 88.5% and 97.8%, respectively, in the group treated for more than 1 year. The 10-year DFS and OS were 89.6% and 92.6%, respectively, in the group treated with imatinib for less than 3 years and 88.0% and 100.0%, respectively, in the group treated with imatinib for more than 3 years. Conclusion:The overall prognosis of primary, non-gastric, low recurrence risk GISTs is relatively favorable; however, recurrences and metastases do occur. Age, tumor diameter, Ki67, and R1 resection may affect the prognosis. For some patients with low risk GISTs, administration of adjuvant therapy with imatinib for an appropriate duration may help prevent recurrence and improve survival.

Objective:To analyze the etiology of chronic pancreatitis(CP) and evaluate the impact of different intervention methods on the prognosis.Methods:This is a retrospective analysis conducted on clinical data of pediatric patients with CP admitted to Beijing Children's Hospital between January 2010 and December 2023,including etiology,clinical manifestations,imaging data and treatments.Follow-up assessments included height,weight,complications occurrence,and long-term nutritional status evaluated by using Z scores.Results:A total of 98 patients with CP were included in the study,containing 51 males and 47 females,with an age range of 1.95 to 15.96 years (median 8.49 years).The etiological contained the gene mutation (39.8%,39/98) (involving PRSS1, SPINK1, CFTR),the anatomical abnormality (26/98,26.5%),idiopathic pancreatitis (33.7%,33/98).Predominant clinical manifestations included abdominal pain (79/98,79.6%),nausea/vomit(48/98,49.0%),chest tightness/chest pain (10/98,10.2%),with malnutrition (44/98,44.9%) and the serum amylase increased in some patients.Imaging findings revealed heterogeneous pancreatic echoes,dilated pancreatic ducts and pancreatic stones via abdominal ultrasound,and a full or atrophic pancreas with irregular margins,tortuous or dilated pancreatic ducts through abdominal magnetic resonance imaging.Compared with CP caused by other reasons,hereditdry CP had a higher rate of pancreatic morphological changes(100.0% vs.88.1%, P<0.05).By March 2024,follow-up showed all 98 patients underwent initial medical treatment,followed by surgical intervention in 13 cases,endoscopic retrograde cholangiopancreatography intervention in 51 cases,and no surgical or endoscopic intervention in 34 cases.Six children developed diabetes,six had reduced fecal pancreatic elastase-1 but without fat diarrhea.Long-term follow-up indicated improved nutritional status among children who underwent endoscopic retrograde cholangiopancreatography intervention(Z score,-1.22 vs.0.74, P<0.001). Conclusion:Gene mutations and anatomical abnormalities is the main etiological factors in pediatric patients with CP.Early endoscopic intervention can significantly improve the long-term prognosis of the children.

AIM:To explore the effect and mechanism of the interfering Gal-1 on epithelial-mesenchymal transition(EMT),migration and proliferation in MDA-MB-231 cells via transforming growth factor-β(TGF-β)pathway.METHODS:The stable cell lines(shGal-1)which Gal-1 expression were inhibited completely and their control cell lines were used as experimental cells.Western blot assay was used to detect the effects of shGal-1 on EMT process of MDA-MB-231 cells after TGF-β treatment;The effect of shGal-1 on cell migration and invasion after TGF-β treatment was verified by cell scratch and transwell test;The effect of shGal-1 on the TGF-β pathway related proteins were detected by western blot;Finally,the effect of shGal-1 on cell proliferation was detected by MTT and western blot.RESULTS:shGal-1 inhib-ited TGF-β-mediated EMT in MDA-MB-231 cells and regulated phosphorylation of pathway signaling molecules(ERK,AKT and GSK3β);shGal-1 could inhibit the proliferation of MDA-MB-231 cells.CONCLUSION:shGal-1 can inhibit the TGF-β-mediated EMT,migration and proliferation of MDA-MB-231 cells.

Objective:To investigate the effects of Houttuynize Herba decoction on aspirin-induced gastric ulcer (GU) in mice; To discuss its mechanism.Methods:A total of 64 SPF male mice were selected, and 48 mice were randomly selected to establish the model by gavage of 20 mg/ml aspirin solution. The remaining 16 rats were treated as normal group by gavage with the same amount of normalsaline once a day for 7 consecutive days. After successful modeling, the remaining mice in the model group were randomly divided into 5 groups, with 8 mice in each group, namely normal saline group (given normal saline), omeprazole group (given omeprazole 0.5 mg/ml), Houttuynize Herba high-, medium- and low-dosage groups (given 1.08 g/ml, 0.54 g/ml, 0.27 g/ml), and the remaining 8 mice in the normal group were given the same amount of normal saline by gavage. The mice were treated by gavage once a day for 7 days. The number of Escherichia coli and Bifidobacterium in mouse feces was counted by bacterial culture method, and the ratio of Bifidobacterium to Escherichia coli (B/E value) was used to judge the imbalance of bacterial flora. The expression of interleukin-6 (IL-6) in serum was detected by magnetic particle chemiluminescence. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression of prostaglandin E 2 (PGE 2) in the serum of mice to determine the level of inflammation. Hematoxylin-eosin staining was used to determine the ulcer and healing. ImageJ 1.8.0 was used to calculate the ulcer inhibition rate. The protein expression levels of IκBα, NF-κB-p65 subunit and phosphorylated IκBα (p-IκBα) and p65 (p-NF-κB-p65) subunits in gastric tissue of mice were evaluated by Western blot. Results:Compared with the normal group, the epithelial cells of the gastric mucosa were missing, the glands were irregularly arranged, and the tissue structure was severely damaged in the modeling group; the number of Escherichia coli in the intestine increased ( P<0.01), the number of Bifidobacterium decreased ( P<0.01), and the B/E value was less than 1 ( P<0.01); Serum PGE2 levels were decreased ( P<0.01), IL-6 levels were increased ( P<0.01); The expression of p-IκBα and p-NF-κB-p65 proteins in gastric tissues was elevated ( P<0.05). After 7 days of drug treatment, compared with the saline group, gastric mucosal cells and structures were improved, and weight gained in the Houttuynize Herba groups ( P<0.05); the rate of inhibition of ulcers in mice in the Houttuynize Herba high-dosage group was significantly improved ( P<0.01); the number of Bifidobacteria in the intestinal tract significantly increased ( P<0.01), that of Escherichia coli was diminished ( P<0.05), B/E value was greater than 1 ( P<0.05), IL-6 content in peripheral blood was reduced ( P<0.05), PGE 2 levels significantly increased ( P<0.01); the level of p-IκBα/IκBα and p-NF-κB-p65/NF-κB-p65 in the gastric tissues of mice decreased ( P<0.01). Conclusion:Houttuynize Herba decoction can effectively improve gastric mucosal injury in mice, and its mechanism may be related to regulating intestinal microorganisms, inhibiting the opening of IκBα/NF-κB pathway, and reducing inflammatory response.