Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Objective:To investigate the spectrum and antimicrobial resistance of major pathogens causing nosocomial infections in China during 2020-2021.Methods:A total of 1 311 non-duplicated nosocomial pathogens causing bloodstream infections (BSI, n=670), hospital-acquired pneumonia (HAP, n=394) and intra-abdominal infections (IAI, n=297) were collected from 10 teaching hospitals across China. The minimum inhibitory concentrations (MICs) of clinical common strains were determined using agar dilution or broth microdilution method. Interpretation of reults followed the CLSI M100-Ed33 criteria, with data analysis conducted using WHONET-5.6 software. The Chi-square test was used to compare rates. Results:The most prevalent pathogens causing BSI were Escherichia coli (21.2%, 142/670), Klebsiella pneumoniae (14.9%, 100/670) and Staphylococcus aureus (11.5%, 77/670); the most prevalent pathogens causing HAP were K. pneumoniae (27.7%, 109/394), Acinetobacter baumanii (22.1%, 87/394) and Pseudomonas aeruginosa (18.3%, 72/394). IN IAI, E. coli (24.3%, 60/247), Enterococcus faecium and K. pneumoniae (both 14.6%, 36/247) were dominated. All S. aureus strains were susceptible to tigecycline, linezolid, daptomycin and glycopeptides. Rates of methicillin-resistant S. aureus (MRSA) and coagulase-negative Staphylococcus (MRCNS) were 36.5% (42/115) and 74.5% (38/51), respectively. The rate of vancomycin-resistant E. faecium and E. faecalis was 3.3% (3/90) and 1.9% (1/53), respectively. The prevalence of extended-spectrum β-lactamase (ESBL) was 23.7% (58/245) in K. pneumonia and 60.5% (130/215) in E. coli.The rate of carbapenem-resistant K. pneumonia and E. coli was 29.8% (73/245) and 4.2% (9/215), respectively; the percentage of tigecycline-resistant K. pneumonia and E. coli was 1.6% (4/245) and 0, respectively; the rate of colistin-resistant K. pneumonia and E. coli was 1.6% (4/245) and 2.8% (6/215), respectively; the percentage of ceftazidime/avibactam-resistant K. pneumonia and E. coli was 2.0% (5/245) and 2.3% (5/215), respectively. The rate of carbapenem-resistant A. baumanii and P. aeruginosa was 76.7% (125/163) and 28.4% (33/116), respectively. A. baumanii showed low susceptibility to most antimicrobial agents except colistin (98.8%, 161/163) and tigecycline (89.6%, 146/163). Colistin, amikacin and ceftazidime/avibactam demonstrated high antibacterial activity against P. aeruginosa with susceptility rates of 99.1% (115/116), 94.0% (109/116) and 83.6% (97/116), respectively. Conclusions:The major pathogens of nosocomial infections were K. pneumonia, E. coli, A. baumanii, P. aeruginosa and S. aureus. Nosocomial Gram-negative pathogens exhibited high susceptibilities to tigecycline, colistin and ceftazidime/avibactam. Antimicrobial resistance in A. baumannii remains a significant challenge. The increasing prevalence of carbapenem-resistant Enterobacterales underscores the urgency of antibiotics rational applications and hospital infection controls.

OBJECTIVE: To explore the clinical manifestations and genetic characteristics of patients with congenital central hypothyroidism due to variants of IGSF1 gene. METHODS: Clinical data, results of genetic testing, and follow-up of four patients admitted to Children's Hospital of Soochow University during 2017 to 2021 were retrospectively analyzed. RESULTS: All of the four patients were males. Patient 1 had presented neonatal jaundice, patients 2 and 3 were admitted for growth retardation during childhood, and thyroid function test indicated slightly low free thyroxine (FT4), patient 4 was found to have reduced FT4 in the neonatal period. Genetic testing revealed that all of the four patients have harbored pathogenic variants of the IGSF1 gene, which were all inherited from their mothers. The thyroid functions in all patients were well controlled with oral levothyroxine and regular follow-up. CONCLUSION Pathogenic variants of the IGSF1 gene probably underlay the congenital central hypothyroidism with a variety of clinical manifestations, and genetic testing can facilitate the diagnosis at an early stage.
Child ; Male ; Infant, Newborn ; Female ; Humans ; Retrospective Studies ; Hypothyroidism/genetics* ; Genetic Testing ; Mothers ; Immunoglobulins/genetics* ; Membrane Proteins/genetics*

To analyze the clinical features and genetic variants of a child with type 4 familial partial lipodystrophy (FPLD4) and the initial manifestation of diabetes.The male patient with the age of 13 years and 5 months, and the diabetes course was about 3 years, the patient was admitted to Children′s Hospital of Soochow University on November 10, 2021(4 th hospitalization at the hospital), in the course of diabetes, the children repeatedly suffered from diabetes ketoacidosis, and lipid metabolism complications gradually emerged.The gene sequencing showed that the proband and his mother carried dual gene mutations of PLIN1 c. 1325delG(p.G442Afs*99) and SPINK1 c. 194+ 2T>C(p.? ). The PLIN1 gene was the causal gene of FPLD4.The mutations of c. 1325delG in the PLIN1 gene had not been previously reported.Based on the clinical phenotype, family history and genetic testing findings, the patient was diagnosed as FPLD4.In addition, the mutation of SPINK1 c. 194+ 2T>C(p.? ) might increase the risk of chronic pancreatitis.This case report enriched the clinical characteristics and genotype data of FPLD4.Gene sequencing assisted the accurate diagnosis of the type of diabetes.The effects of dual gene mutations on disease progression should be concerned, which were of great significance to develop treatment regimen and disease management.

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes(MELAS) is one of the most common inherited mitochondrial diseases. This paper reports a rare mutation associated with MELAS syndrome, the m. 3252 A>G mutation in the MT-TL1 gene encoding the mitochondrial tRNALeu(UUR). The 6-year-old girl suffered from recurrent convulsion and lactic acidemia. The mtDNA sequencing detected a variant m. 3252A>G(MT-TL1 gene) in the proband and her maternal relatives. The heteroplasmic levels in peripheral blood and urine sediment were 66.53% and 97.42%, respectively, which were obviously higher than those of her maternal relatives. Together with 3 previously reported cases, the variant m. 3252A>G could be classified pathogenic. All the reported pathogenic variants in MT-TL1 gene were reviewed to explore the genotype-phenotype correlations of pathogenic variants in MT-TL1 gene.

Objective:To investigate the value of serum insulin-like growth factor-1 (IGF-1), dehydroepiandrosterone sulphate (DHEAS), anti-Müllerian hormone (AMH) and bone morphogenetic protein 6 (BMP-6) in prediction of rapidly progressive puberty(RPP) in girls.Methods:The data of 750 girls who visited the Department of Endocrinology, Metabolism and Genetic Disorders, Children′s Hospital of Soochow University from August 2017 to October 2018 because of breast development were retrospectively analyzed.After following up these girls for 6 months to 1 year, those who were lost to follow up, received early treatment and failed to meet the inclusion criteria were excluded.The remaining 138 girls were divided into the central precocious puberty group (CPP, 32 cases), the early puberty with RPP group (EP-RPP, 33 cases), the early puberty with slow progression puberty group (EP-SPP, 32 cases) and RPP group (41 cases) according to the inclusion criteria.The healthy control group consisted of 33 undeveloped girls aged 8 to 9 who underwent physical examination in the same hospital over the same period.The serum concentrations of IGF-1, DHEAS, AMH and BMP-6 were measured.The general information, clinical manifestations, laboratory examination results and radiological features were compared among different groups.Statistical analysis was performed by using SPSS 22.0, and the receiver operating characteristic curve (ROC) was drawn to investigate the value of IGF-1, DHEAS, AMH and BMP-6 in prediction of RPP.Results:(1)The serum follicle stimulating hormone(FSH) peak value was 15.10(13.86-19.80) IU/L in the EP-SPP group, 11.99(9.18-16.16) IU/L in the EP-RPP group and 11.43(9.37-15.63) IU/L in the RPP group.The ratio of serum FSH/luteinizing hormone(LH) peak values was 3.20(2.44-4.58) in the EP-SPP group, 1.86(1.05-3.16) in the EP-RPP group and 0.76(0.49-0.99) in the RPP group.The serum FSH peak value and the ratio of serum FSH/LH peak values in the EP-SPP group were significant higher than those in the EP-RPP group(all P<0.05). There was no significant difference in the serum FSH peak value between the EP-RPP group and the RPP group( P>0.05). (2)The serum IGF-1 levels of the healthy control group, EP-SPP group, EP-RPP group, CPP group and RPP group were 166.00(126.50-188.00) μg/L, 199.00(170.50-262.50) μg/L, 252.00(233.00-291.50) μg/L, 288.00(252.00-376.00) μg/L and 382.00(264.0-499.50) μg/L, respectively.The serum IGF-1 levels of the EP-SPP group, EP-RPP group, CPP group and RPP group were all significantly higher than those in the healthy control group (all P<0.05). The serum IGF-1 levels in the EP-RPP group were higher than those in the EP-SPP group( P<0.01). As the puberty rapidly progressed, the serum IGF-1 levels gradually increased.The RPP group had the highest IGF-1 levels, and the difference in IGF-1 levels between the RPP group and EP-RPP group was statistically significant( P<0.01). (3)The serum DHEAS levels were 41.65(14.80-59.88) μg/L in the healthy control group, 42.50(30.15-79.83) μg/L in the EP-SPP group, 52.32(43.08-98.54) μg/L in the CPP group, 63.30(34.00-81.55) μg/L in the EP-RPP group and 70.89(51.85-100.02) μg/L in the RPP group.The DHEAS levels of the healthy control group, EP-RPP group and RPP group gradually increased.The RPP group had the highest DHEAS levels.There was significant difference in DHEAS levels among the healthy control group, EP-RPP group and RPP group ( P<0.05). There was no significant difference in DHEAS levels among the EP-SPP group, CPP group and EP-RPP group( P>0.05). (4)The serum AMH and BMP-6 levels in the EP-RPP group, EP-SPP group, RPP group, CPP group and healthy control group were not significantly different( P>0.05). (5)The area under the ROC curve of serum IGF-1 levels was 0.765, the cut-off value was 232.5 μg/L, the specificity for the cut-off value was 83.30%, and the sensitivity was 75.00%.The combined area under the ROC curve of the serum FSH peak value and the ratio of serum FSH/LH peak values was 0.795. Conclusions:Serum IGF-1 levels and the combination of the serum FSH peak value and the ratio of serum FSH/LH peak values can be used as effective indicators of slowly and rapidly progressive puberty in early adolescent girls.Serum DHEAS cannot be used as an early warning index of RPP, but it plays a critical role in the regulation of puberty initiation and process.Serum DHEAS levels may be related to the Tanner stage.

OBJECTIVE: To analyze the clinical and genetic characteristics of five Chinese pedigrees affected with short stature. METHODS: A retrospective analysis was carried out for the clinical data and results of genetic testing for the probands. A literature search was also conducted. RESULTS: The five probands have all featured short stature with a family history. Genetic testing has revealed that they have harbored variants of the ACAN gene, including p.Val2042Argfs*6, p.Val1597del, c.630-1G>A, c.23delT and c.2026+1G>A(previously reported). CONCLUSION Except for short stature, children harboring heterozygous variants of the ACAN gene may have no involvement of other systems. Some of these children may response to short-term growth hormone treatment.
Aggrecans/genetics* ; Body Height/genetics* ; Child ; China ; Genetic Testing ; Humans ; Pedigree ; Retrospective Studies

Objective:To monitor the susceptibility of common used antimicrobial agents against nosocomial Gram-negative bacilli in 2018 across China.Methods:Prospective collection of Gram-negative bacilli from 13 teaching hospitals nationwide from January to December 2018. The minimal inhibitory concentration (MICs) of antibiotics such as meropenem was determined by agar dilution methods and broth microdilution methods. Interpretation of results using the Clinical and Laboratory Standards Institute(CLSI) 2019 M100S (29th Edition) standard. Data were analyzed by using WHONET-5.6 software.Results:A total of 1 214 non-repetitive Gram-negative bacilli were collected, accounting for 96.7% (1 174/1 214) of blood and sterile body fluid samples. The activity of antimicrobial agents against 871 strains of Enterobacteriaceae was as follows in descending order of susceptible rate: amikacin (93.2%, 812/871), meropenem (92.0%, 801/871), ertapenem (88.9%, 774/871), imipenem (88.4%, 770/871), piperacillin-tazobactam (84.0%, 732/871), cefoperazone-sulbactam (83.1%, 724/871), cefepime (71.4%, 622/871), minocyline (68.9%, 600/871), ceftazidime (66.9%, 583/871), levofloxacin (54.4%, 474/871).The resistance rates of Escherichia coli to the third generation cephalosporins were 61.5% (155/252) (ceftriaxone) and 60.7% (153/252) (cefotaxime), respectively. The resistance rates of Klebsiella pneumoniae to the third generation cephalosporins were 56.6% (126/222) (ceftriaxone) and 57.9% (129/222) (cefotaxime), respectively. The incidence of extended-spectrum β lactamase (ESBLs) positive E. coli and K. pneumoniae was 50.2% (127/252) and 18.2% (40/222), respectively. Over 95% of all the ESBLs positive strains were susceptible to imipenem and meropenem. The incidence of carbapenem-resistant Escherichia coli and Klebsiella pneumoniae was 2.8% (7/252) and 20.4% (45/222), respectively. For Enterobacter cloacae, Klebsiella aerogenes, Citrobacter freundii, the most susceptible agent were tigecycline (96.3%-100%), followed by amikacin (94.9%-97.1%), meropenem (89.8%-96.6%)and imipenem (89.8%-94.9%).The susceptibility of Proteus mirabilis, Morganella morganii and Serratia marcescens to meropenem and amikacin was over 90%.A total of 67 strains of carbapenems resistant enterobacteriaceae(CRE) were detected. Modified carbapenem inactivation method showed, 45 strains were serine carbapenemase and 20 were metalloenzymes. The susceptibility of Pseudomonas aeruginosa to meropenem and imipenem were 73.2% (112/153) and 66.0% (101/153), respectively. Acinobacter baumannii has the highest sensitivity to colistin (100%, 163/163), followed by tigecycline (87.1%, 142/163).Compared with other sources of infection, specimens of bloodstream infections were less resistant to Klebsiella pneumoniae (17.6%, 27/153 vs 21.7%, 15/69) and Acinetobacter baumannii (68.3%, 71/104 vs 71.2%, 42/59). Escherichia coli (2.5%,4/198 vs 0%,0/54) and Pseudomonas aeruginosa (37%, 33/89 vs 18.8%, 12/64) have a high proportion of carbapenem resistance. Conclusions:Carbapenems still maintain high antibacterial activity against Enterobacteriaceae bacteria, especially strains producing only ESBLs. Carbapenem-resistant Klebsiella pneumoniae should be given sufficient attention. Carbapenemase is the most important drug resistance mechanism of carbapenem-resistant Enterobacteriaceae in China.

Objective:To investigate the clinical and genetic characteristics of a boy with Ulnar-Mammary syndrome(UMS), and to review the literature.Methods:The clinical and genetic data of a boy with UMS, who was admitted to the Department of Endocrinology, Genetics and Metabolism, Children′s Hospital of Soochow University in May 2018 were analyzed. Original papers on UMS published up to July 2019 were retrieved.Results:A male patient at the age of 12 years and 8 months visited us for growth retardation. He presented with high forehead, epicanthic folds, broad nasal tip, anteverted nostrils, high palate, dental crowding, mammary gland hypoplasia, and absence of axillary hairs, with height 148.9 cm(<-1 SD). Growth hormone stimulation test indicated growth hormone deficiency(growth hormone peak <5 ng/ml). After one year of treatment with recombinant human growth hormone, his height was improved. Gene sequencing identified a de novo heterozygous mutation of TBX3 c. 711DelC(p.N238Mfs* 4). According to ACMG guidelines in 2015, the mutation is pathogenic and has not been reported in the above databases.However, this mutation was not detected in his parents.Conclusion:UMS should be considered in dwarfism with special face, dysplasia of external genitalia, sweat glands, and mammary glands, and TBX3 is a pathogenic gene.

Objective: To analyze the epidemiological history, clinical manifestations, treatment and the short-term prognosis of 31 cases of 2019 novel coronavirus(2019-nCoV) infection in children from six provinces (autonomous region) in northern China. Methods: A retrospective analysis of the epidemiological history, clinical symptoms, signs, laboratory examinations, chest imaging, treatment and the short-term prognosis of 31 cases of 2019-nCoV was conducted. The patients were diagnosed between January 25th, 2020 and February 21st, 2020 in 21 hospitals in 17 cities of six provinces(autonomous region) of Shaanxi, Gansu, Ningxia, Hebei, Henan and Shandong. Results: The age of the 31 children with 2019-nCoV infection was 7 years and 1 month (6 months -17 years). Nine cases (29%) were imported cases. Other 21 cases (68%) had contact with confirmed infected adults. One case (3%) had contact with asymptomatic returnees from Wuhan. Among the 31 children, 28 patients (90%) were family cluster cases. The clinical types were asymptomatic type in 4 cases (13%), mild type in 13 cases (42%), and common type in 14 cases (45%). No severe or critical type existed. The most common symptom was fever (n=20, 65%), including 1 case of high fever, 9 cases of moderate fever, 10 cases of low fever. Fever lasted from 1 day to 9 days. The fever of fifteen cases lasted for ≤3 d, while in other 5 cases lasted > 3 d. Other symptoms included cough (n=14, 45%), fatigue (n=3, 10%) and diarrhea (n=3, 9%). Pharyngalgia, runny nose, dizziness, headache and vomiting were rare. In the early stage, the total leukocytes count in peripheral blood decreased in 2 cases (6%), the lymphocytes count decreased in 2 cases (6%), and the platelet count increased in 2 cases (6%).Elevation of C-reactive protein (10%, 3/30), erythrocyte sedimentation rate(19%,4/21), procalcitonin(4%,1/28), liver enzyme(22%, 6/27) and muscle enzyme (15%, 4/27) occurred in different proportions. Renal function and blood glucose were normal. There were abnormal chest CT changes in 14 cases, including 9 cases with patchy ground glass opacities and nodules, mostly located in the lower lobe of both lungs near the pleural area. After receiving supportive treatment, the viral nucleic acid turned negative in 25 cases within 7-23 days. Among them, 24 children (77%) recovered and were discharged from hospital. No death occurred. Conclusions In this case series, 2019-nCoV infections in children from six provinces (autonomous region) in northern China are mainly caused by close family contact. Clinical types are asymptomatic, mild and common types. Clinical manifestations and laboratory examination results are nonspecific. Close contact history of epidemiology, nucleic acid detection and chest imaging are important bases for diagnosis. After general treatment, the short-term prognosis is good.