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 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.

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 difference and reliability of blood 17-hydroxyprogesterone (17-OHP), an indirect screening index for congenital adrenal hyperplasia (CAH), between preterm and full-term infants.Methods:In this retrospective cross-sectional study, a total of 210 285 newborns who underwent CAH screening at the Neonatal Screening Center of Shanghai Children′s Hospital from January 2019 to December 2022 were collected, including 14 312 premature infants and 195 973 full-term infants.The concentration of 17-OHP in dried blood spots on filter paper was determined by an automatic fluorescence analyzer.The distribution of 17-OHP levels in preterm and full-term infants and its statistical index 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 by the interquartile range method.The cumulative frequency distribution map was drawn by R language programming.The 99.5 th percentile value was used as the screening threshold and compared with the reference value given by the manufacturer or laboratory and with the reference change value (RCV). Results:According to the threshold provided by the laboratory, 26.76‰ of premature infants were tested positive in preliminary screening, and 4 were confirmed with an incidence of 1∶3 578, while 0.79‰ of full-term infants were tested positive in preliminary screening, and 11 were confirmed with an incidence of 1∶17 816.The thresholds for CAH screening established indirectly were 20.35 nmol/L in preterm infants and 10.78 nmol/L in full-term infants.The relative deviations between the indirect CAH screening thresholds and the manufacturer′s or laboratory′s CAH screening thresholds were higher than the RCV, respectively.According to the indirect CAH screening thresholds, the negative and positive coincidence rates of 65 samples in 13 batches from the Centers for Disease Control and Prevention interlaboratory quality assessment program in the United States reached 100%.A retrospective analysis of 210 285 neonates showed that 17-OHP concentration was higher than the screening threshold in all CAH-positive neonates.The application of this screening threshold reduced the false positive rate of preterm infants by 59.79%.Conclusions:It is feasible to establish the CAH screening thresholds for premature and full-term infants by an indirect method, which can improve the efficiency of screening and provide better diagnostic basis for clinical practice.

Objective:To investigate the impact of Adiponectin receptor agonists(AdipoRon)on renal aging induced by D-galactose(D-gal)in male C57BL/6J mice and explore potential mechanisms.Methods:Male C57BL/6J mice were randomly divided into three groups: a control group, a D-gal model group, and an AdipoRon group, each consisting of ten mice.The control group received saline through gavage and subcutaneous injection, the D-gal group received saline through gavage and D-gal through subcutaneous injection, and the AdipoRon group received AdipoRon through gavage and D-gal through subcutaneous injection.The treatment duration was eight weeks, following which blood and renal tissues were collected for testing.Kidney pathological changes were observed using Haematoxylin-Eosin(HE)staining, Masson staining, and electron microscopy.Levels of serum creatinine(SCr), urea nitrogen(BUN), and cystatin-C(Cys-C)in mice were measured using an automatic biochemical analyzer.Protein expression levels of P53, P21, P16INK4a, Silent mating-type information regulation 2 homolog 1(SIRT1), Nuclear factor E2-related factor 2(NRF2), and Klotho in renal tissues were determined through Immunohistochemical staining and Western blot.Results:The glomeruli exhibited sparse and irregular structure, with sclerosis and dilated capsular space.Renal tubules showed atrophy, while foot processes appeared fused and widened.A significant presence of blue-stained collagen fibers was noted in the renal interstitium of the D-gal group compared to the control group.Pathological damage to the kidneys was notably reduced in the AdipoRon group compared to the D-gal group.Levels of SCr(23.13±2.21 μmol/L), BUN(19.58±1.63 μmol/L), and Cys-C(0.15±0.02 μmol/L)were higher in the D-gal group than in the control group.Conversely, SCr(16.97±1.16 μmol/L), BUN(16.25±1.25 μmol/L), and Cys-C(0.12±0.01 μmol/L)levels in the AdipoRon group were lower than those in the D-gal group( F=66.61, 40.37, 48.77, all P<0.001).The expression levels of aging proteins like P53(1.68±0.11), P21(2.40±0.45), and P16INK4a(1.89±0.16)in the mice kidney tissue of the D-gal group were elevated compared to the control group.In contrast, anti-aging proteins such as SIRT1(0.46±0.04), NRF2(0.65±0.05), and Klotho(0.42±0.03)were decreased in the D-gal group versus the control group.The expression levels of aging proteins like P53(1.27±0.06), P21(1.84±0.35), and P16INK4a(1.10±0.14)in the AdipoRon group were reduced.Conversely, the expression levels of anti-aging proteins such as SIRT1(0.78±0.05), NRF2(0.87±0.07), and Klotho(0.65±0.06)were increased compared to the D-gal group( F=152.38, 44.45, 147.54, 219.69, 42.25, 166.49, all P<0.001). Conclusions:AdipoRon was found to potentially slow down D-gal-induced renal senescence in mice through activation of the SIRT1 signaling pathway.

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.