Objective:To identify pathogenic genes in 3 cases of piebaldism, and to explore the genotype-phenotype relationships in piebaldism.Methods:Clinical data were collected from 3 patients with piebaldism and their parents at the Department of Dermatology, Henan Provincial People′s Hospital from January 2019 to December 2021. Peripheral blood samples were obtained from them and 100 unrelated healthy controls, and DNA was extracted. Whole-exome sequencing technology was used to screen genetic variation sites, and then Sanger sequencing was performed for verification. The deleteriousness of genetic variants was evaluated by using pathogenicity analysis software tools.Results:Case 1: a 23-year-old male patient presented with white patches on the forehead, chest, and abdomen for 23 years, and his parents had no similar symptoms; case 2: a 1-year- and 5-month-old male infant presented with white patches on the forehead and abdomen for 1 year, and his parents had no similar symptoms; case 3: a 6-year-old male child presented with white patches on the forehead and limbs for 6 years, and his parents had no similar clinical manifestations. Genetic testing showed that a missense mutation c.2033T>C (p.L678P) in exon 14 of the KIT gene, a splice site mutation c.2485-1G>C in exon 18 of the KIT gene, and a heterozygous missense mutation c.2346C>G (p.F782L) in exon 16 of the KIT gene were identified in the case 1, 2, 3 respectively, but no above mutations were identified in the patients′ parents or 100 unrelated healthy controls. The 3 genetic variants were all novel pathogenic mutations, and all were deleterious mutations.Conclusions:Three novel pathogenic mutations in the KIT gene were identified in the 3 cases of piebaldism, namely c.2033T>C (p.L678P), c.2485-1G>C, and c.2346C>G (p.F782L). It was further verified that the severity of piebaldism was closely related to the type and location of KIT gene mutations.

Lysinuric protein intolerance (LPI) is a rare autosomal recessive disorder involving digestive, renal, respiratory, and nervous systems caused by SLC7A7 gene mutation.It was first reported in Finland and now has been found worldwide.A total of 8 cases have been reported in China.The abnormal function of the y + amino acid transporter caused by SLC7A7 gene mutation can explain some clinical features, but the pathophysiological mechanism underlying the associated lung, kidney and blood system disorders is not clear.The varying clinical manifestations of LPI often lead to misdiagnosis or delayed diagnosis.This article reviews the pathogenesis, clinical characteristics, diagnosis and treatment of LPI, to enhance clinicians′ understanding of this disease.

Objective:To analyze the factors affecting delayed chemotherapy in children with Burkitt lymphoma (BL) and their influence on prognosis.Methods:Retrospective cohort study. Clinical data of 591 children aged ≤18 years with BL from May 2017 to December 2022 in China Net Childhood Lymphoma (CNCL) was collected. The patients were treated according to the protocol CNCL-BL-2017. According to the clinical characteristics, therapeutic regimen was divided into group A, group B and group C .Based on whether the total chemotherapy time was delayed, patients were divided into two groups: the delayed chemotherapy group and the non-delayed chemotherapy group. Based on the total delayed time of chemotherapy, patients in group C were divided into non-delayed chemotherapy group, 1-7 days delayed group and more than 7 days delayed group. Relationships between delayed chemotherapy and gender, age, tumor lysis syndrome before chemotherapy, bone marrow involvement, disease group (B/C group), serum lactate dehydrogenase (LDH) > 4 times than normal, grade Ⅲ-Ⅳ myelosuppression after chemotherapy, minimal residual disease in the interim assessment, and severe infection (including severe pneumonia, sepsis, meningitis, chickenpox, etc.) were analyzed. Logistic analysis was used to identify the relevant factors. Kaplan-Meier method was used to analyze the patients' survival information. Log-Rank was used for comparison between groups.Results:Among 591 patients, 504 were males and 87 were females, the follow-up time was 34.8 (18.6,50.1) months. The 3-year overall survival (OS) rate was (92.5±1.1)%,and the 3-year event-free survival (EFS) rate was (90.5±1.2)%. Seventy-three (12.4%) patients were in delayed chemotherapy group and 518 (87.6%) patients were in non-delayed chemotherapy group. The reasons for chemotherapy delay included 72 cases (98.6%) of severe infection, 65 cases (89.0%) of bone marrow suppression, 35 cases (47.9%) of organ dysfunction, 22 cases (30.1%) of tumor lysis syndrome,etc. There were 7 cases of chemotherapy delay in group B, which were seen in COPADM (vincristine+cyclophosphamide+prednisone+daunorubicin+methotrexate+intrathecal injection,4 cases) and CYM (methotrexate+cytarabine+intrathecal injection,3 cases) stages. There were 66 cases of chemotherapy delay in group C, which were common in COPADM (28 cases) and CYVE 1 (low dose cytarabine+high dose cytarabine+etoposide+methotrexate, 12 cases) stages. Multinomial Logistic regression analysis showed that the age over 10 years old ( OR=0.54,95% CI 0.30-0.93), tumor lysis syndrome before chemotherapy ( OR=0.48,95% CI 0.27-0.84) and grade Ⅲ-Ⅳ myelosuppression after chemotherapy ( OR=0.55,95% CI 0.33-0.91)were independent risk factors for chemotherapy delay.The 3-year OS rate and the 3-year EFS rate of children with Burkitt lymphoma in the delayed chemotherapy group were lower than those in the non-delayed chemotherapy group ((79.4±4.9)% vs. (94.2±1.1)%, (80.2±4.8)% vs. (92.0±1.2)%,both P<0.05). The 3-year OS rate of the group C with chemotherapy delay >7 days (42 cases) was lower than that of the group with chemotherapy delay of 1-7 days (22 cases) and the non-delay group (399 cases) ((76.7±6.9)% vs. (81.8±8.2)% vs. (92.7±1.3)%, P=0.002).The 3-year OS rate of the chemotherapy delay group (9 cases) in the COP (vincristine+cyclophosphamide+prednisone) phase was lower than that of the non-chemotherapy delay group (454 cases) ((66.7±15.7)% vs. (91.3±1.4)%, P=0.005). Similarly, the 3-year OS rate of the chemotherapy delay group (11 cases) in the COPADM1 phase was lower than that of the non-chemotherapy delay group (452 cases) ((63.6±14.5)% vs. (91.5±1.3)%, P=0.001). Conclusions:The delayed chemotherapy was related to the age over 10 years old, tumor lysis syndrome before chemotherapy and grade Ⅲ-Ⅳ myelosuppression after chemotherapy in pediatric BL. There is a significant relationship between delayed chemotherapy and prognosis of BL in children.

Humans ; Multiple Myeloma/genetics* ; Karyotyping ; Translocation, Genetic/genetics*

Objective: To analyze the epidemiological characteristics of pulmonary tuberculosis among students in Wuhan from 2011 to 2020, and to provide a basis for the scientific development of interventions and strategies. Methods: Epidemiological distribution, time of onset and treatment, as well as treatment outcomes of student tuberculosis in Wuhan from 2011 to 2020 registered in the national tuberculosis information management system were described. Results: During 2011-2020, 4 337 student tuberculosis patients in Wuhan were registered. The average annual incidence rate was 22.44/10 million, and the annual decreasing rate of 7.86% The incidence of male and female patients was 1.76:1, and the incidence rate of male was higher than that of female( χ 2=184.18, P <0.01). Most of patients aged 19-22 years old, accounting for 47.89%; Tuberculosis reports were highest during March to May, and September to November, and lowest during January to February, and July to August. Student patients were mainly concentrated in Hongshan District, Jiangxia District and Wuchang District, where schools were more distributed in Hongshan District, Dongxihu District, Wuchang District and Xinzhou District. The median duration from tuberculosis onset to treatment was 9(3, 21) days, which varied significantly by region, age, nationality, and patient residence ( Z =-9.25, 47.14, 9.88,43.96, P <0.01). The treatment and outcome of student tuberculosis patients were varied significantly by year and nationality( P <0.05). Conclusion The incidence of student tuberculosis in Wuhan City showed a slow downward trend. Most of student tuberculosis are college and high school students. Time and place of case detection are relatively fixed. The time of treatment and the outcome of treatment vary significantly. Tuberculosis prevention and control strategies should be formulated according to the local conditions according to the tuberculosis distribution characteristics, as well as enhancing surveillance, health promotion, active discovery and supervision management of tuberculosis in school settings.

Objective:To analyze and compare the clinical indicators and the liver failure-related prognostic score of patients with amanita phalloides poisoning with different prognoses, and to explore potential prognostic indicators.Methods:A retrospective case-control study was conducted. The clinical data of 52 patients with amanita phalloides poisoning admitted to the department of emergency of Xijing Hospital Affiliated to Air Force Medical University from September 2016 to September 2021 were collected, including general information (gender, age), clinical indicators at admission [mean arterial pressure (MAP), total bilirubin (TBil), aspartate transaminase (AST), alanine transaminase (ALT), albumin (ALB), serum creatinine (SCr), blood urea nitrogen (BUN), creatine kinase (CK), D-dimer, fibrinogen degradation product (FDP), prothrombin time (PT), activated partial thromboplastin time (APTT), prothrombin activity (PTA), international normalized ratio (INR), white blood cell count (WBC), platelet count (PLT)], liver failure-related prognostic score [sequential organ failure assessment (SOFA), chronic liver failure (CLIF)-SOFA score, European Foundation for the Study of Chronic Liver Failure-organ failure (CLIF-C OF)], and 28-day outcome. The clinical indicators and liver failure-related prognostic scores of the patients with different prognoses were compared. Receiver operator characteristic curve (ROC curve) was used to determine the prognostic value of statistically significant indicators between different prognosis of patients with amanita poisoning.Results:A total of 45 patients were enrolled, of which 38 survived and 7 died within 28 days. The coagulation indicators including PT, APTT, INR, and liver failure-related prognostic scores including SOFA score, CLIF-SOFA score, and CLIF-C OF score in the patients of death group were significantly higher than those in the survival group [PT (s): 69.59±15.94 vs. 25.99±4.64, APTT (s): 83.44±17.82 vs. 42.64±3.79, INR: 6.13±1.47 vs. 2.07±0.33, SOFA score: 11.57±1.38 vs. 6.03±0.77, CLIF-SOFA score: 9.86±2.17 vs. 5.55±0.67, CLIF-C OF score: 11.71±0.97 vs. 8.37±0.35], and PLT was significantly lowered (×10 9/L: 80.57±29.65 vs. 169.60±11.80, all P < 0.05). ROC curves showed that coagulation indicators including PT, APTT, INR, PLT, and liver failure-related prognostic scores including SOFA score and CLIF-C OF score were associated with the prognosis of patients with amanita phalloides poisoning, with the area under the ROC curve (AUC) of > 0.75. The sensitivity of the clinical indicators was above 85%, and the AUC and specificity of INR were the highest, which were 0.88 [95% confidence interval (95% CI) was 0.74-1.00] and 83.0%, respectively; meanwhile, the sensitivity of the liver failure-related prognostic scores was 100%, and the AUC and specificity of the CLIF-C OF score were the highest, which were 0.86 (95% CI was 0.74-0.99) and 66.0%, respectively. Conclusion:INR and CLIF-C OF score can be used to evaluate the poor prognosis of patients with amanita phalloides poisoning.

Objective:This study aimed to explore variables associated with remission rate and survival in patients with acute myeloid leukemia (AML) after induction failure and relapse.Methods:Data of 373 consecutive patients with AML were analyzed after induction failure and relapse. Binary logistics and the Cox model regression were used to identify variables associated with remission rate and outcomes.Results:In patients with AML after induction failure and relapse, the total CR+CRi rates were 50.6% and 40.3%, respectively; among those who achieved CR/CRi, the 3-year RFS rates were 34.4% and 30.4%, respectively, and the 3-year overall survival rates were 40.1% and 31.6%, respectively. In the multivariate analyses, using CLAG or FLAG regimen as a re-induction chemotherapy regimen, age <39 years and SWOG low-risk were significantly associated with higher remission rates in patients with induction failure. Male, secondary AML, SWOG high-risk, the interval from the first remission to relapse within 12 months, and bone marrow blasts ≥20% at the time of relapse were significantly associated with lower remission rates in relapsed patients. Transplantation was significantly associated with prolonged relapse-free survival and overall survival in patients achieving hematologic remission; the SWOG low-risk group was significantly associated with longer overall survival in those with induction failure; and achieving CR (not CRi) or having female gender was associated with longer RFS or overall survival in relapsed patients.Conclusion:Reinduction chemotherapy regimen, age, gender, SWOG risk, secondary AML, the interval from the first remission to relapse, and bone marrow blast percentage at the time of relapse were significantly associated with remission rates in the patients with AML after induction failure and relapse. Transplantation, SWOG low-risk, achieving CR, or female gender were associated with longer survivals in those achieving remission.

Objective:To analyze the efficacy and safety of Daratumumab for the treatment of primary AL light chain systemic amyloidosis.Methods:Twenty one patients who were diagnosed as primary AL light chain systemic amyloidosis and treated with Daratumumab from 7 centers were retrospectively analyzed. Daratumumab was administrated as first line therapy in seven patients and 14 patients with relapsed settings. Hematological response, safety and survival were analyzed.Results:All 7 patients achieved very good partial response (VGPR) or better with first-line application of daratumumab. Three patients died, and the other four achieved organ remission. Among 14 relapsed patients, 2 patients had a difference of free light chain (dFLC) less than 20 mg/L before treatment, and 9 with a dFLC of more than 50 mg/L. All patients reached partial response (PR) or better, including 4 patients with complete response (CR), 3 with VGPR and 2 with PR. The response rate was 100% in 3 patients with dFLC 20-50 mg/L at baseline. The organ remission rate was 50% in patients with heart involvement and 58.3% in patients with kidney impairment. The overall median follow-up period was 5.3 months, and 11 months in surviving patients. One patient died of severe infection and disseminated intravascular coagulation (DIC) with stable amyloidosis. One patient switched to other regimens because dFLC elevated but did not fulfill progressive disease after 2 year application. As to safety, no grade 3/4 infusion reaction developed, and grade 1 infusion reaction occurred in 3 cases during the first infusion. Lymphocytopenia was seen in 75% patients including grade 3 or more in 30% patients.Conclusion:Daratumumab is effective to eliminate serum free light chain in both newly diagnosed and relapsed patients with systemic amyloidosis.

Objective:To analyze the clinical and chest CT features in a family with interstitial lung disease(ILD), and assess the probable causative gene mutations for the family.Methods:In order to identify the etiology of the proband′s ILD, the pedigree was investigated.The clinical data of five proband′s pedigree members were collected, and the chest HRCT examination was performed on four proband′s pedigree members with respiratory symptoms.The human whole exon sequencing was performed on the proband′s blood samples, then its deleterious effects were assessed.Subsequently, the strong pathogenic mutation was validated by Sanger sequencing.Results:According to the family survey, there were five patients with ILD in the family, including three males and two females.One of them died.The surfactant protein C(SFTPC)gene(exon4, c.342G>T, p.K114N)was found in all four surviving patients.The mutation was considered to be originated from the father of the proband, and the pathogenic mutation was considered, which was not included in the databases and was a noval mutation.In addition, the clinical manifestations of different patients in the family were significantly different.Conclusion:The novel mutation of p. k114n in SFTPC gene can lead to ILD in children, and the mutation has incomplete exons in family members.Chest CT and whole exon sequencing play an important role in the diagnosis of ILD in children.

Objective: To evaluate the long-term ef efficacy and safety of topical 1% atropine for retarding pregressive myopia. Methods: A randomized controlled study evaluating atropine and placebo in 570 Chinese children aged 8~14 years recruited from pediatric ophthalmology in Yunnan Provincial the Second People s Hospital during Jan. 2015 to Dec. 2019. In experimental group, patients received drops every two weeks for 24 months, then every three weeks for 12 months, followed by no drops for 12 months. In control group, all children wear single focus frame glasses. Spherical equivalent, axial length, intraocular pressure and atropinerelated side effects were examined at 6, 12, 24, 36 and 48 months for all children. Results: At the end of stage Ⅰ, the myopia progression in the atropine treatment group (-0.27±0.81)D was significantly lower than that in the control group (-1.29±0.13)D, and the increase of axial length in the atropine group (0.11±0.13)mm was also significantly lower than that in the control group (0.41±0.19)mm (P<0.05). At the end of stage Ⅱ, the average myopia progression in the atropine treatment group (-0.31±0.28)D was significantly lower than that in the control group (-0.80±0.66)D (P<0.01). Similarly, the axial growth of the experimental group (0.14±0.09)mm was significantly lower than that of the control group (0.39±0.14)mm (P<0.01). After the withdrawal of atropine eye drops (stage Ⅲ), there was no significant refractive regression in the experimental group. During the whole follow-up period, no serious adverse events related to atropine were found. Conclusion Local intermittent use of 1% atropine eye drops and the gradual reduction of atropine eye drops can ensure the effectiveness in the treatment of myopia, reducing the side effects of atropine, avoiding refractive regression after drug withdrawal, and improving children s compliance at the same time.