Autophagy is a cellular self-degradation process essential for maintaining metabolic functions in cells and organisms.Dysfunc-tional autophagy has been linked to various diseases,including cancer.The m6A modification,a major RNA modification in eukaryotes,plays a crucial role in regulating autophagy in tumor cells by regulating the expression of autophagy-associated genes(ATGs)or interfering with autophagy-related signaling pathways.Aberrant m6A modification can lead to dysregulated autophagy and impact tumor progression.However,the specific role of m6A in regulating tumor autophagy remains to be explored.Therefore,in this review,we discuss the role of m6A modification in tumor cell autophagy and examine its relationship with tumor progression and drug resistance,aiming to provide a the-oretical foundation for developing new therapeutic strategies.

ObjectiveTo observe the effect of transcranial direct current stimulation (tDCS) combined with task-oriented rehabilitation training single pellet reaching and grasping (SPG) on the motor function of forelimb in rats with unilateral contusion of C₅ spinal cord. MethodsA total of 60 adult male Sprague-Dawley rats were randomly divided into sham operation group (sham group), spinal cord injury (SCI) group, tDCS group, SPG group, false group and tDCS+SPG group, with ten rats in each group. Only C₅ lamina was removed in the sham group, and the C₅ spinal cord contusion model was established by IH spinal cord impactor in the other five groups. The rats received tDCS in tDCS group, SPG in SPG group, tDCS without current in false group, tDCS combined with SPG in tDCS+SPG group, and no treatment in the SCI and the sham groups. The rats were evaluated with Rearing and Grooming tests, and motor-evoked potential (MEP). ResultsFour weeks after operation, compared with SCI group, the scores of Rearing and Grooming increased in tDCS group and tDCS+SPG group (P < 0.05), and they were more in the tDCS+SPG group than in tDCS group and SPG group (P < 0.05); the score of Grooming increased in SPG group (P < 0.05); while the amplitude of MEP increased in tDCS group, SPG group and tDCS+SPG group (P < 0.05), and the latency shortened in tDCS group and tDCS+SPG group (P < 0.05); and the amplitude increased more in tDCS+SPG group than in tDCS group and SPG group (P < 0.01). ConclusiontDCS could promote the recovery of motor function in rats with SCI, and the combination therapy of tDCS and task-oriented rehabilitation training is more effective.

Objective To investigate the prevalence and influencing factors of thyroid nodules in children aged 8-10 years in Suzhou , and to provide a scientific basis for the rational prevention and treatment of iodine deficiency disorders (IDD). Methods PPS sampling method was used in this study. Questionnaire survey, physical examination and thyroid B-ultrasound examination were conducted on students aged 8-10 years. Salt samples and urine samples were collected for laboratory detection of the salt iodine and urinary iodine. Univariate and multivariate logistic regression models were used to analyze the risk factors related to thyroid nodules. Results A total of 2 048 children aged 8-10 years were included in the present survey, and the prevalence of thyroid nodules was 23.34% (478/2 048). The prevalence of nodules in boys was 20.98% (218/1 039), and the prevalence of nodules in girls was 25.77% (260/1 009). Multivariate analysis showed that gender (OR=1.338, P=0.006), height (OR=1.993, P=0.001), frequency of iodine-rich food intake (OR=0.862, P=0.048) and nutritional supplements (OR=1.469, P=0.008) were correlated with the prevalence of thyroid nodules. Conclusion The prevalence rate of thyroid nodules in children aged 8-10 years old in Suzhou is 23.34%. Female gender, higher height, regular intake of iodine-rich foods and dietary supplements are statistically associated with the prevalence of thyroid nodules, which may be risk factors for the prevalence of thyroid nodules , but further research is needed to confirm.

Objective:To investigate the size of thyroid of children aged 8 - 10 in Suzhou City and explore its influencing factors.Methods:According to the requirements of the "Jiangsu Province Iodine Deficiency Disorders Monitoring Plan", a stratified multi-stage sampling method was conducted in 10 counties (cities, districts) under the jurisdiction of Suzhou City in five directions: east, west, south, north, and middle from May 2019 to July 2020. Forty children aged 8 - 10 (age balanced, half male and half female) were selected from each primary school for thyroid volume examination, height and weight measurement, and questionnaire survey. At the same time, salt samples from children's homes and random urine samples were collected for iodine content testing, and explore the influencing factors of the thyroid volume.Results:A total of 2 046 children aged 8 - 10 were selected, including 1 038 boys and 1 008 girls. The thyroid volume of children was (3.183 ± 1.042) ml, while the total goiter rate (TGR) was 2.93% (60/2 046). Univariate analysis showed that there were statistically significant differences in thyroid volume among groups with different age, height, weight, body mass index (BMI), presence or absence of nodules, and different dietary frequencies (eating solid snacks, iodine-rich foods, cruciferous vegetables, and meat at different frequencies, P < 0.05). Correlation analysis showed that thyroid volume was positively correlated with age, height, weight, BMI, body surface area (BSA), thyroid nodules, consumption of iodine-rich foods and cruciferous vegetables ( r = 0.24, 0.34, 0.32, 0.21, 0.35, 0.19, 0.05, 0.04, P < 0.05), while negatively correlated with consumption of meat ( r = - 0.04, P = 0.047). Multivariate linear regression analysis showed that age, BSA, thyroid nodules, consumption of solid snacks and cruciferous vegetables entered the equation, with standardized partial regression coefficient values were 0.11, 0.30, 0.16, 0.05, 0.05, respectively. Conclusions:The thyroid volume of children aged 8 - 10 in Suzhou City is not only influenced by age, but also by factors such as BSA, thyroid nodules, consumption of solid snacks, and cruciferous vegetables.

Objective:To evaluate the activity of iduronate-2-sulfatase (IDS) in fetal villi and peripheral blood plasma of pregnant women at high risk of mucopolysaccharidosis type Ⅱ (MPS Ⅱ), and to discuss the application of gene analysis in prenatal diagnosis of MPS Ⅱ.Methods:The enzymatic testing and gene analysis results of 23 pregnant women at high risk of MPS Ⅱ, who underwent prenatal diagnosis in Guangzhou Women and Children′s Medical Center from February 2013 to December 2020, were analyzed retrospectively.The IDS activity in fetal villi (30 cases) and plasma (28 cases) was detected by artificial substrate fluorescence.The IDS activity in fetal villi (28 cases) and plasma (34 cases) of normal pregnant women was taken as control.Meanwhile, the fetal villi of both pregnant women at high risk of MPS Ⅱ and normal pregnant women were also analyzed by gene testing and for fetal sex identification.Data were compared between groups by the independent samples t test. Results:The normal reference values of the IDS activity in fetal villi and plasma of normal pregnant women were(71.2±23.4) nmol/(mg·4 h) and (611.1±114.5) nmol/(mL·4 h), respectively.Among the 30 cases of high-risk fetal villi, the IDS activity in fetal villi of 8 affected male fetuses was (1.7±0.3) nmol/(mg·4 h), which was significantly lower than that of 11 unaffected male fetuses (83.2±6.3) nmol/(mg·4 h) and that of 9 non-carrier female fetuses (80.0±7.5) nmol/(mg·4 h) ( t=10.8, 8.8; all P<0.01). Meanwhile, the IDS activity was measured in the maternal peripheral plasma of 28 pregnant women at high risk of MPS Ⅱ.Among them, the IDS activity in 8 affected male fetuses was(225.4±20.5) nmol/(mL·4 h), which was significantly lower than that in non-affected male fetuses[(451.0±15.1) nmol/(mL·4 h)] and that in non-carrier female fetuses[(467.7±45.3)nmol/(mL·4 h)]. Eight known pathogenic mutations were found in 30 cases at high risk of MPS Ⅱ of fetal villi, and the mutation types were c. 1048A>C, c.212G>A, c.514C>T, c.257C>T, c.425C>T, and c. 998C>T.Of the 8 cases, 6 affected male fetuses had significantly reduced IDS activities, and the other 2 female carriers had normal IDS enzyme activities. Conclusions:The IDS activity in fetal villi and peripheral plasma of pregnant woman is consistent with the gene analysis results.The IDS activity has an important reference value for the prenatal diagnosis of MPS Ⅱ in the first trimester.When no genetic mutations are found in the probands or the pathogenicity of the new mutation remains unclear, the IDS activity in fetal villi can be detected separately for the prenatal diagnosis of MPS Ⅱ.

Objective To explore the iodine nutritional status among school-age children within 5 years of implementation of the new salt iodine standard in Suzhou, and to provide a basis for dynamically adjusting the salt iodization strategy. Methods The observation period (2012-2019) was divided into two sub-periods: the adjustment transition period (2012-2014) and the adjustment completion period (2015-2019). According to the ^“Jiangsu Iodine Deficiency Disease Surveillance Program^”, household salt samples and urine samples of school-age children aged 8 to 10 years were collected to detect the content of salt iodine and urine iodine. The coverage rate of iodized salt, qualified iodized salt consumption rate, and the median urinary iodine were determined. Results Totally 2 893 and 9 132 salt samples were collected in the adjustment transition and adjustment completion periods, with the median salt iodine content being 26.50 and 23.20 mg/kg, respectively. The iodized salt coverage rates were 97.03% (2 807/2 893) and 91.01% (2 633/2 893), and the consumption rates of qualified iodized salt were 97.25% (8 881/9 132) and 93.93% (8 578/9 132), respectively, in the two periods. The differences between the coverage rate of iodized salt and the consumption rate of qualified iodized salt between the two periods were statistically significant (χ²=38.465, P<0.01), and showed an upward trend (χ² trend= 17.528, P<0.01). During the adjustment transition period, the median urinary iodine content of school-age children in Suzhou was 215.61 μg/L , and the proportion of urine iodine value <50 μg/L was 1.5%, while during the adjustment completion period the median urinary iodine and proportion of urine iodine value <50 μg/L were 192.60 μg/L and 2.40%, respectively. The difference in urine iodine between the two periods was statistically significant (Z=-9.918, P<0.01); Conclusions Five years after the implementation of the new salt iodization standard, the iodine nutritional level of school-age children in Suzhou was generally at an appropriate level. However, there was no significant changes in iodine nutritional levels in some areas after the adjustment of the new standard, suggesting that surveillance on iodine nutrition should be continuously consolidated in the future.

Objectives:To explore the GAA varient spectrum and the genotype-phenotype correlations in patients with glycogen storage disease type Ⅱ (Pompe disease, PD), as well as to estimate the disease incidence based on carrier rate of GAA varients in Guangzhou population.Methods:A total of 57 PD cases were retrospectively enrolled at Guangzhou Women and Children′s Medical Center from January 1, 2010 to May 31, 2020. All patients presented symptoms before the age of 18 years. Each diagnosis was further confirmed by GAA enzyme activity and GAA variants. The carrier rate of GAA varients was calculated based on variants detected by whole exon sequencing among 2 395 healthy children in Guangzhou.Results:Among the 57 PD patients (including male 26, female 31),twenty-eight patients with infantile onset PD (IOPD) presented with progressive general muscle weakness and cardiomyopathy. The mean ages of symptom onset and diagnosis were (2.5±1.4) and (5.0±3.0) months, respectively. Twenty-six cases died in the first year after birth.Twenty-three patients with late onset PD (LOPD) presented with progressive muscle weakness. Seven of them had respiratory failure at diagnosis. The mean ages of symptom onset and diagnosis were (12.0±5.0) and (17.0±7.5) years, respectively. Six children with atypical IOPD showed motor delay, muscle weakness and cardiomyopathy. Their diagnosis was confirmed at 2.5-7.0 years of age. Among the 57 patients, 47 different variants were identified in the GAA gene. Three variants: c.797C>T, c.1109G>A and c.1757C>T were novel. c.1935C>A (25/114, 21.9%) and c.2238G>C (15/114, 13.2%) were the most common variants, detected in 57.1% of IOPD and 65.2% (15/23) of LOPD patients, respectively. Among the 28 IOPD patients, 26 cases (92.9%) carried at least one missense variant which indicated positive cross-reactive immunologic material (CRIM). The carrier rate of pathogenic variants in GAA gene among healthy children was 24/2 395. The estimated incidence of PD in this population is about 1/40 000. The frequencies of pseudodeficiency variants c.1726G>A and c.2065G>A homozygotes were 26.3% (15/57) and 35.1% (20/57) in PD patients, which were significantly higher than those (1.7% (40/2 395) and 3.9% (94/2 395)) in healthy children (χ2=151.2, 121.9; both P<0.01). Conclusions:PD presents as a spectrum, some as atypical IOPD. The c.1935C>A and c.2238G>C are common variants, correlated with IOPD and LOPD respectively. The c.796C>T and c.1082C>T are usually found in atypical IOPD. The majority of IOPD patients is predicted to be CRIM positive. The estimated incidence of PD is about 1/40 000.

Objective: To study the efficacy, safety and long-term outcomes of integrated strategy of bortezomib-based induction regimens followed by autologous hematopoietic stem cell (ASCT) and maintenance therapy in Chinese multiple myeloma (MM) patients. Methods: 200 MM patients receiving integrated strategy of bortezomib--based induction regimens followed by ASCT and maintenance therapy were retrospectively and prospectively analyzed from December 1. 2006 to April 30. 2018. Results: The complete remission rates (CR) and better than very good partial remission rates (VGPR) after induction therapy, transplantation and maintenance therapy were respectively 31% and 75.5%, 51.8% and 87.7%,73.6% and 93.4%. There was no difference between 4 cycles and more than 5 cycles induction chemotherapy. The negative rate of MRD detection by flow cytometry was 17.6% and 38.2% respectively after induction and 3 months after transplantation. The negative rate of MRD gradually increased during the maintenance therapy. The success rate of high dose CTX combined with G-CSF mobilization was 95.5% and transplantation related mortality (TRM) was zero. The median time to progress (TTP) was 75.3 months and the median overall survival (OS) was 99.5 months. TTP of patients obtaining CR and negative MRD after induction were longer that those of no CR and positive MRD. TTP and OS of patients receiving triple-drug induction and ASCT in early stage were longer than those of double-drug induction and ASCT in late stage. LDH≥240 U/L, high risk cytogenetics, ISS II+III stage and HBsAg positive were prognostic factors at diagnosis. However, only MRD and high risk cytogenetics were independent prognostic factors after transplantation and maintenance therapy. The clinical characteristics of patients of TTP ≥6 years were listed below: light-chain type M protein, ISS I stage, normal level of hemoglobin and platelet, normal LDH, HBsAg negative, chromosome 17p-negative, good response and sustained good response. Conclusions Integrated strategy of bortezomib-based induction regimens followed by ASCT and maintenance therapy can significantly improve the short-term and long-term efficacy. The prognostic factors of TTP in different disease stages were different. Response to treatment, especially MRD, played a more important role in prognostic factors.

Objective To evaluate the sensitivity and specificity of enzyme assays,and to provide disease spectrum of lysosomal storage diseases (LSDs).Methods Three thousand three hundred and sixty-four high risk individuals were screened for 24 LSDs at Guangzhou Women and Children's Medical Center between January 2009 and December 2016.Twenty-two kinds of enzyme activities from peripheral blood leucocytes or plasma were measured by using the fluorometry or colorimetry of corresponding artificial substrates,screening for 24 LSDs diseases.Measurement data were represented by (x) ± s,and count data were expressed as a percentage or composition ratio.Results A total of 283 subjects were diagnosed with 18 different kinds of LSDs,and the positive rate of high-risk screening was 8.4％.Among the identified patients,172 cases (60.8％) were mucopolysaccharidosis (MPS),79 cases (27.9％) were sphingolipidoses,18 cases (6.4％) were Pompe diseases,10 cases (3.5％) were affected with mucolipidoses,3 cases (1.1％) were glycoprotein storage diseases,and 1 case(0.4％) was Wolman disease.Of the MPS cases,there were 75 cases of MPS Ⅱ (43.6％),45 cases of MP5 ⅣA (26.2％),24 cases of MPS Ⅵ (14.0％) and 20 cases of MPS Ⅰ (11.6％).Gaucher disease (23/79 cases,29.1％) and metachromatic leukodystrophy (MLD) (21/79 cases,26.6％) were common in sphingolipidoses group.Both the sensitivity and specificity of enzyme assays on peripheral blood leucocytes for LSDs were 100％.Conclusions The most common kinds of LSDs are MPS Ⅱ,MPS Ⅳ A,MPS Ⅵ,Gaucher disease,MLD and Pompe disease.Leukocyte enzymology analysis of high-risk screening LSDs has high sensitivity and specificity.

Objectives To explore the clinical and gene mutation characteristics of Gitelman syndrome in children. Method The clinical data of 3 children with Gitelman syndrome were retrospectively analyzed. Results All three cases were male and their age were 3, 8 and 10 years . The clinical manifestations were hypokalemia, hypomagnesemia, alkalosis, hyperreninemia,and hyperaldosteronemia.Gene detection revealed a complex heterozygous mutation in the SLC12A3 gene.A total of 5 mutation sites were found in the SLC12A3 gene,c.179C>T(Thr60Met),c.248 G>A(Arg83Gln),c.2129 C>A(Ser710X), c.2660+1G>A, c.1456G>A (Asp486Asn). After the diagnosis was confirmed, they were treated with potassium supplement, magnesium supplement, and spironolactone and the conditions were improved in all cases. Conclusions In children with hypokalemia, be aware of Gitelman syndrome, and gene detection is helpful for the diagnosis.