BACKGROUND:U937 cells can be used as a cell model for studying the biological characteristics,signaling pathways,and therapeutic targets of acute myeloid leukemia.Although it has been reported that long non-coding RNA KIAA0125 is highly expressed in acute myeloid leukemia,its biological function in U937 cells remains unclear,and its mechanism of action in the occurrence and development of acute myeloid leukemia needs to be further clarified. OBJECTIVE:To investigate the expression level of long non-coding RNA KIAA0125 in peripheral blood of patients with acute myeloid leukemia and its effect on the proliferation and apoptosis of U937 cells. METHODS:RNA-sequencing was used to analyze the bone marrow monocyte samples from acute myeloid leukemia patients,and the differentially expressed gene long non-coding RNA KIAA0125 was screened.The expression of long non-coding RNA KIAA0125 in peripheral blood of patients with acute myeloid leukemia was detected by qRT-PCR.The relationship between long non-coding RNA KIAA0125 mRNA expression and prognosis in bone marrow cells of 173 acute myeloid leukemia patients and 70 healthy people was statistically analyzed by GEPIA database.Subsequently,recombinant lentivirus technology and CRISPR/Cas9-SAM technology were used to construct U937 cell lines with knockdown/overexpression of long non-coding RNA KIAA0125.qRT-PCR was used to detect the knockdown/overexpression efficiency of long non-coding RNA KIAA0125.Next,CCK-8 assay,flow cytometry,and western blot assay were used to detect the effects of knockdown/overexpression of long non-coding RNA KIAA0125 on the proliferation and apoptosis of U937 cells.Finally,western blot assay was used to detect the effect of knockdown/overexpressed long non-coding RNA KIAA0125 on Wnt/β-catenin signaling pathway-related proteins. RESULTS AND CONCLUSION:(1)The results of qRT-PCR showed that long non-coding RNA KIAA0125 was highly expressed in peripheral blood of acute myeloid leukemia patients.The results of GEPIA database showed that long non-coding RNA KIAA0125 was highly expressed in bone marrow cells of acute myeloid leukemia patients,and the high expression group had worse overall survival.(2)The knockdown efficiency of long non-coding RNA KIAA0125 in knockdown group was 70%,and the U937 cells that stably down-regulated long non-coding RNA KIAA0125 expression were successfully constructed.The expression of long non-coding RNA KIAA0125 in overexpression group was four times that of vector group,and stable U937 cells were successfully constructed.(3)Knockdown of long non-coding RNA KIAA0125 inhibited the proliferation of U937 cells and promoted their apoptosis.Overexpression of long non-coding RNA KIAA0125 promoted the proliferation of U937 cells but had no significant effect on the apoptosis of U937 cells.(4)Knockdown of long non-coding RNA KIAA0125 inhibited the activity of Wnt/β-catenin signaling pathway,while overexpression of long non-coding RNA KIAA0125 activated Wnt/β-catenin signaling pathway.These results confirm that long non-coding RNA KIAA0125 is highly expressed in acute myeloid leukemia peripheral blood.Long non-coding RNA KIAA0125 may affect the proliferation and apoptosis of U937 cells by regulating the Wnt/β-catenin signaling pathway,and may be a potential prognostic marker for acute myeloid leukemia.

Solanum nigrum is a traditional Chinese herb widely distributed in China. It is rich in active ingredients such as alkaloids and saponins， and has shown remarkable hepatoprotective effects and various mechanisms in the treatment of various liver diseases. It can prevent and treat chemical liver injury through anti-inflammatory， antioxidant， gut microbiota-regulating， and anti- fibrotic pathways. In the prevention and treatment of fatty liver disease， it can regulate lipid metabolism， inhibit lipogenesis， and promote fat degradation. It has potential antiviral activity against viral hepatitis. By inducing tumor cell apoptosis， arresting the cell cycle， and inhibiting tumor cell proliferation and metastasis and so on， it plays a role in the prevention and treatment of liver cancer. Clinically， S. nigrum has been used in the treatment of liver cancer and liver fibrosis after chronic hepatitis B， showing good efficacy and high safety. Future research should focus on further elucidating its mechanisms of action and promoting the development and application of new drugs， in order to benefit more patients with liver diseases.

Objective: To explore the growth characteristics of rat calvaria by detecting the calvaria of SD rats in different periods. Methods: The calvaria of SD rats at 1 , 4 , 7 , 10 , and 12 weeks from the same littermate were selected (3 rats per week) . Real⁃time PCR and Western blot techniques were used to detect the expression of focal adhesion kinase ( FAK) Ⅳ phosphatidylinositol 3 kinase/protein kinase B ( PI3K/AKT ) signal pathway in the calvaria , and the role of FAK⁃PI3K/AKT in the growth and development of the calvaria was analyzed by correlation. Results: The increase of brain volume and the thickness of calvaria increased synchronously , the expression of FAK was positively correlated with the changes of meridians , and the expression of FAK was positively correlated with the expression of PI3K/AKT. Conclusion The expression of FAK is related to the growth and development of rat skull. FAK plays a role in calvaria by activating PI3K/AKT signal pathway. FAK may be used as a marker of rapid skull growth and development , which provides a basic theoretical basis for the timing of clinical skull defect repair and treatment.

Objective:To investigate the risk factors and prognosis of varicella zoster virus (VZV) infection in children with thalassemia after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:The clinical data of 446 children with thalassemia who underwent allo-HSCT from January 2012 to December 2020 in the Department of Hematology and Oncology, Shenzhen Children′s Hospital were retrospectively collected.The clinical features of the patients with VZV infection were analyzed.The patients were divided into different groups according to whether they had VZV infection.Categorical variables between groups were compared using the chi- square tests to investigate the risk factors that were associated with the development of VZV.Survival time was analyzed by the Kaplan-Meier method. Results:VZV incidence was 4.3% (19/446 cases), and the median onset time was 5 months (1.5-11.0 months) after allo-HSCT.Of the 19 cases with VZV infection, 5 cases were complicated with VZV encephalitis.All cases were treated with antiviral agents (Acyclovir alone, or both Acyclovir and Foscarnet), intravenous immunoglobulin and external use of Acyclovir ointment.After 7-28 days of treatment (median treatment time: 14 days), all of their herpes subsided, and the neurological symptoms of patients with VZV encephalitis disappeared.One of the 19 children died.The death was not directly caused by VZV infection, but by secondary graft dysfunction and severe pneumonia 5 months after VZV infection.The incidence of VZV infection following allo-HSCT in children with thalassemia was related to the age of the donor ( P=0.010), but not to the age of the patient ( P=0.378), gender ( P=0.653), disease grade of thalassemia ( P=0.912), type of the donor ( P=0.205), source of stem cells ( P=0.624) and acute graft versus host disease ( P=0.277). VZV infection had no significant effect on the prognosis of thalassemia children after allo-HSCT ( P=0.241). Conclusions:Thalassemia children with VZV infection after allo-HSCT are prone to be complicated with VZV encephalitis.Cord blood transplantation is a high risk factor.VZV infection may not have an impact on survival of children with thalassemia after allo-HSCT.

Objective:To explore the expressions of programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) and clinicopathological characteristics in post-transplant lymphoproliferative disorder (PTLD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children, with the aim of clarifying whether checkpoint inhibition of PD-1/PD-L1 inhibitors may serve as a therapy option.Methods:The clinical data of 13 cases of PTLD after allo-HSCT pathologically confirmed in Shenzhen Children′s Hospital from January 1, 2012 to December 30, 2019 were retrospectively analyzed.The detection was performed by immunohistochemical staining by MaxVision? method, Epstein-Barr virus(EBV) in situ hybridization and lymphoma gene rearrangement.The relationship between the expression of PD-1 and PD-L1 and the clinicopathological characteristics of PTLD were analyzed.Results:The expression of PD-1 was not correlated with gender, age, primary diseases, histopathological types, transplantation mode and the expression of EBV in situ hybridization (all P>0.05). The expression of PD-L1 was correlated with histopathological types ( P<0.05). Furthermore, the expression rate of PD-L1 on severe β-thalassemia was significantly higher than that of severe aplastic anemia [90.0%(9/10 cases) vs. 66.7%(2/3 cases)] and monomorphic PTLD was higher than that of polymorphic PTLD [100.0%(2/2 cases) vs. 83.3%(5/6 cases)]. Moreover, the positive PTLD in EBV was higher than the negative PTLD in EBV [90.9%(10/11 cases) vs. 50.0%(1/2 cases)]. The positive rates of PD-1 and PD-L1 in 13 cases with PTLD were 46.2%(6/13 cases) and 61.5%(8/13 cases) in tumor cells, 92.3% (12/13 cases) and 76.9% (10/13 cases) in microenvironmental cells, and 84.6%(11/13 cases) in EBV, respectively. Conclusions:PD-L1 has a higher positive rate in tumor cells with monomorphic PTLD; and routine staining for PD-1 and PD-L1 can be performed in all types of PTLD when standard immunotherapy and chemotherapy are ineffective.

Objective:To study the effectiveness of noninvasive embryo chromosome screening (NICS) based on blastocyst culture medium and cystic fluid in preimplantation genetic detection (PGT) of embryos in different age groups.Methods:A retrospective analysis of 62 couples who underwent PGT assisted pregnancy in Shenzhen Hospital of Peking University from January 2019 to June 2021. A total of 310 blastocysts were biopsied. At the same time, D3-6 blastocyst culture medium and blastocyst cavity fluid were collected for NICS. According to the age of the patients, they were divided into three groups: <35 years old group, 35≤age<40 years old group and ≥40 years old group. The results of NICS were compared with those of embryonic trophoblast (TE) biopsy in each group, and the consistency, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated. Then the consistency, sensitivity, specificity, positive predictive value and negative predictive value of NICS and TE among the three age groups were statistically analyzed.Results:There was no statistically significant difference in the consistency rate of NICS and TE among the three age groups ( P>0.05), but there was an upward trend in the elderly group (35≤age<40 years and ≥40 years). There was no statistically significant difference in specificity, sensitivity and PPV among the three age groups ( P>0.05). There was significant difference in NPV between the ≥40 years group and the other two groups ( P<0.05). Conclusions:There was no statistical difference in the effectiveness of NICS among different age groups, However, there was an increasing trend in people ≥35 years of age.

OBJECTIVE: To investigate the genetic etiology, clinical diagnosis and treatment of a child with pancytopenia, failure to thrive and pulmonary infection. METHODS: Peripheral blood samples of the child and her parents were collected. Genomic DNA was extracted. Genetic variants associated with hematological diseases were detected by high-throughput sequencing. RESULTS: Three variants of TCN2 gene were found, one of which located in exon 5 upstream(c.581-8A>T), the parents has carried this variant; one in exon 6 (c.924_927del), the variant was originated from the mother; one in exon 7 (c.973C>T), the variant has ocurred de novo. The variants pathogenic analysis combined with clinical manifestation, pancytopenia, the increase in methylmalonic acid level and increased homocysteine, the child was diagnosed with transcobalaminIIdeficiency. The patient presented with respiratory infection, which was confirmed to be pneumocystosis by lung radioscopy and pathogenic high-throughput sequencing of broncho-alveolar lavage fluid. The patient presented with acute respiratory distress syndrome during the treatment with intramuscular injection of vitamin B CONCLUSION We reported a case of Chinese child with TCNII deficiency due to novel gene variant, and analyzed the pathogenicity of the three variants. The treatment of TCNII deficiency with cobalamin should be individualized.
Amino Acid Metabolism, Inborn Errors ; Child ; Female ; Genetic Testing ; Humans ; Rare Diseases ; Transcobalamins/genetics* ; Vitamin B 12

Targeted therapeutic drug,having such advantages as targeting,safety,convenience,etc,is increasingly favored by non-small cell lung cancer (NSCLC) patients.At present,there are many kinds of molecular targeted drugs used in clinic,and remarkable efficacy was achieved,and the pain caused by conventional chemotherapy was avoided.At the same time,with the deepening of the understanding of the mechanism of tumor immune,new targeted drugs will also continue to be developed.The emergence of the third generation EGFR-TKI brings new hope for first generation EGFR-TKI resistant patients.Combined use of different immune therapeutic agents,combined application of immunotherapy drugs and cytotoxic chemotherapy drugs and radiotherapy,and the exploration of its predictive biomarkers will become a hot spot in the research of lung cancer.This will undoubtedly bring a new dawn for the treatment of NSCLC.Based on the domestic and foreign research literatures and related materials,this article reviews the latest research progress of various molecular targeted drugs for treatment of NSCLC.

OBJECTIVE:To provide reference for promoting rational use of vancomycin in the clinic. METHODS:Referring to vancomycin instruction,Guiding Principles for Clinical Use of Antibacterials (2015 edition) and Chinese Expert Consensus on Clinical Use of Vancomycin (2011 edition),720 inpatient medical records of vancomycin were collected from our hospital during Jan. 2013-Dec. 2014,and then drug use of those inpatients were analyzed retrospectively. RESULTS:Among 720 cases,male (428 cases)was more than female(292 cases),and most of them aged 41-65(45.83%). There were 50 cases of prophylactic drug use(6.94%)and 670 cases of therapeutic drug use(93.06%). The patients came from 36 departments. Among 720 cases,the dose of 19 cases were higher than 2 g/d,and there were 13 ADR cases(1.81%). Among 670 cases of therapeutic drug use,587 cases of microbiological samples (87.61%) were detected,and other antibacterials were used in 522 cases additionally (77.91%). DUI of vancomycin was equal to 0.96 in 549 cases no younger than 18 years old of herapeutic drug use. There were 240 cases of unsuit-able drug use (33.33%) in total,including 192 cases of unsuitable solvent (26.67%),28 cases of unsuitable usage and dosage (3.89%)and 20 cases of unsuitable drug combination(2.78%). CONCLUSIONS:The use of vancomycin in our hospital is basi-cally rational;vancomycin is widely used in departments;drug combination is a common phenomenon;the inspection rate of mi-crobiological samples is qualified;no drug abuse is found. However,there still is inappropriate use in the clinic. It is recommended to strengthen special evaluation and training about rational use of vancomycin,and further standardize monitoring for vancomycin use so as to guarantee the safety of drug use.

OBJECTIVE:To provide reference for solving the shortage of national essential medicines in Changchun. METH-ODS:According to preliminary work,a questionnaire was conducted to investigate and statistically analyze the shortage situation of essential medicines in 22 higher than secondary and 50 basic medical and health institutions in Changchun;ABC analysis was used to analyze the national essential medicines in shortage;the bid results and shortage causes of the primary and secondary nation-al essential medicines in shortage were inquired. RESULTS:Totally 72 questionnaire were send out,and 72 were recycled with ef-fective recovery of 100%. The investigation results showed there were 19 shortage breeds(22 dosage forms),which lost the bid-ding,and 99 breeds(111 dosage forms)of national essential medicines in shortage,which won the bidding,including 85 kinds of chemical medicines and biological products,14 kinds of Chinese patent medicine in Changchun. Cardiovascular system drugs shows the largest number in the bid chemical medicines and biological products,and the Chinese patent medicine were mainly Fu-zheng agent and Quyu agent(internal medicine). Results of ABC analysis showed,among the 111 bid shortage dosage forms,17 were primary and 23 were secondary. The main causes for them were price raising in raw materials,lack of production,no produc-ing in manufacturers and purchase price higher than winning bids. CONCLUSIONS:Low accessibility of raw material drugs,low enthusiasm to production,lower drug price than a reasonable level,and small clinical requirements can lead to the shortage of na-tional essential medicines. It is suggested to intensify in supervising the raw materials’marketing,raising the enthusiasm of manu-facturers,perfecting the system of drug bidding,developing fixed-point production and building drug reserve system to guarantee the production and supply of national essential medicines,and satisfy clinical demands.