Clinical and gene mutation characteristics of patients with hereditary ellipsocytosis: nine cases report and literature review / 中华血液学杂志

Objective: To report gene mutations in nine patients with hereditary elliptocytosis (HE) and analyze the characteristics of pathogenic gene mutations in HE. Methods: The clinical and gene mutations of nine patients clinically diagnosed with HE at Institute of Hematology & Blood Diseases Hospital from June 2018 to February 2022 were reported and verified by next-generation sequencing to analyze the relationship between gene mutations and clinical phenotypes. Results: Erythrocyte membrane protein gene mutations were detected among nine patients with HE, including six with SPTA1 mutation, one with SPTB mutation, one with EPB41 mutation, and one with chromosome 20 copy deletion. A total of 11 gene mutation sites were involved, including 6 known mutations and 5 novel mutations. The five novel mutations included SPTA1: c.1247A>C (p. K416T) in exon 9, c.1891delG (p. A631fs*17) in exon 15, E6-E12 Del; SPTB: c.154C>T (p. R52W) ; and EPB41: c.1636A>G (p. I546V) . Three of the six patients with the SPTA1 mutation were SPTA1 exon 9 mutation. Conclusion: SPTA1 is the most common mutant gene in patients with HE.

Caries status and related factors among 12-year-old children in Yangpu District， Shanghai / 上海预防医学

ObjectiveTo investigate the prevalence and risk factors of dental caries and its related influencing factors in 12-year-old children in Yangpu District， Shanghai， and to provide relevant data support for the formulation of oral health policies and measures for children. MethodsIn 2021， 839 12-year-old children were randomly selected from five ordinary junior high schools in Yangpu District. The investigation included an oral health examination and a questionnaire survey on factors related to dental caries. Logistic regression analysis was used to analyze the influencing factors of dental caries. ResultsAmong the 839 participants， data from 830 were included. Among them， 426 were male （51.3%） and 404 were female （48.7%）. Of the 830 children， 203 had dental caries， resulting in a caries prevalence of 24.46%， a caries supplemental filling ratio of 32.6%， and a DMFT of 0.63. Multivariate logistic regression analysis revealed that a mother’s education level of college or above （OR=0.849，95% CI： 0.732‒0.984）， brushing teeth twice a day （OR=0.827，95%CI： 0.703‒0.973）， and the caregiver brushing teeth twice a day （OR=0.843， 95%CI： 0.726‒0.983） were effective factors in reducing the caries rate. Factors associated with childhood dental caries included consuming sweets ≥1 time per day （OR=1.397，95%CI： 1.197‒1.342） and female gender （OR=1.482，95%CI： 1.347‒1.671）. ConclusionThe prevalence of dental caries among 12-year-old children in Yangpu District is 24.46%. Gender， maternal education， the frequency of children's toothbrushing， the frequency of sweet consumption， and the caregiver’s toothbrushing frequency are the main factors affecting the prevalence of dental caries in children.

Optimization of parameters for stir-frying of Kansui Radix with vinegar based on conversion of toxic components / 中国中药杂志

This study aims to optimize the parameters for stir-frying of Kansui Radix with vinegar based on the conversion of representative toxic diterpenes, which is expected to serve as a reference for the standardized production of Kansui Radix stir-fried with vinegar. To be specific, the toxic components [3-O-(2'E,4'Z-decadienoyl)-20-O-acetylingenol(3-O-EZ), kansuiphorin C(KPC)] in Kansui Radix and the products(ingenol, 20-deoxyingenol) after the stir-frying with vinegar were selected. The toxicity to intestine and water-draining activity were evaluated with NCM460(normal human colon mucosal epithelial cell line) and HT-29(a human colorectal adenocarcinoma cell line). An HPLC method was then developed to assess the conversion of toxic components. On this basis, temperature, time, and amount of vinegar for the processing of Kansui Radix were optimized with the Box-Behnken design and the content of ingenol and 20-deoxyingenol as evaluation index. The results showed that after the stir-frying of Kansui Radix with vinegar, 3-O-EZ and KPC were first converted to monoester 3-O-(2'E,4'Z-decadienoyl)ingenol(3-EZ) and 5-O-benzoyl-20-deoxyingenol(5-O-Ben) and finally to almost non-toxic ingenol and 20-deoxyingenol, respectively. Meanwhile, the water-draining activity was retained. Six compounds had a good linear relationship with the peak area in the corresponding concentration ranges(R~2≥0.999 8), and the average recovery fell in the range of 98.20%-102.3%(RSD≤2.4%). The content of representative diterpenes and intermediate products was 14.78%-24.67% lower in the Kansui Radix stir-fried with vinegar than in the Kansui Radix, while the content of the conversed products was 14.37%-71.37% higher. Among the process parameters, temperature had significant influence on the total content of products, followed by time. The optimal parameters were 210 ℃, 15 min, and 30% vinegar. The relative error between the experimental results and the predicted values was 1.68%, indicating that the process was stable and reproducible. The strategy of screening optimal parameters for stir-frying of Kansui Radix with vinegar based on the transformation of toxic components can help improve the production stability, reduce the toxicity, and ensure the efficacy of Kansui Radix stir-fried with vinegar, which can serve as a reference for the process optimization of similar toxic Chinese medicinals.

Jujubae Fructus alleviates intestinal injury caused by toxic medicinals in Shizao Decoction based on correlation between intestinal flora and host metabolism / 中国中药杂志

Genkwa Fols, Kansui Radix, and Euphorbiae Pekinensis Radix in Shizao Decoction(SZD) are toxic to intestinal tract. Jujubae Fructus in this prescription can alleviate the toxicity, but the mechanism is still unclear. Therefore, this study aims to explore the mechanism. To be specific, 40 normal Sprague-Dawley(SD) rats were classified into the normal group, high-dose and low-dose SZD groups, and high-dose and low-dose SZD without Jujubae Fructus(SZD-JF) groups. The SZD groups were given(ig) SZD, while SZD-JF groups received the decoction without Jujubae Fructus. The variation of body weight and spleen index were recorded. The patho-logical changes of intestinal tissue were observed based on hematoxylin and eosin(HE) staining. The content of malondialdehyde(MDA) and glutathione(GSH) and activity of superoxide dismutase(SOD) in intestinal tissue were measured to evaluate the intestinal injury. Fresh feces of rats were collected to detect intestinal flora structure by 16S ribosomal RNA gene(16S rDNA) sequencing technology. The content of fecal short chain fatty acids and fecal metabolites was determined by gas chromatography-mass spectrometer(GC-MS) and liquid chromatography-mass spectrometer ultra-fast liquid chromatography-quadrupole-time-of-flight mass spectrometer(UFLC-Q-TOF-MS), separately. Spearman's correlation analysis was employed to analyze the differential bacteria genera and differential metabolites. RESULTS:: showed that high-dose and low-dose SZD-JF groups had high content of MDA in intestinal tissue, low GSH content and SOD activity, short intestinal villi(P<0.05), low diversity and abundance of intestinal flora, variation in the intestinal flora structure, and low content of short chain fatty acids(P<0.05) compared with the normal group. Compared with high-dose and low-dose SZD-JF groups, high-dose and low-dose SZD groups displayed low content of MDA in intestinal tissue, high GSH content and SOD activity, recovery of the length of intestinal villi, increased abundance and diversity of intestinal flora, alleviation of dysbacteria, and recovery of the content of short chain fatty acids(P<0.05). According to the variation of intestinal flora and fecal metabolites after the addition of Jujubae Fructus, 6 differential bacterial genera(Lactobacillus, Butyricimonas, Clostridia＿UCG-014, Prevotella, Escherichia-Shigella, Alistipes),4 differential short chain fatty acids(such as acetic acid, propionic acid, butyric acid, valeric acid) and 18 differential metabolites(such as urolithin A, lithocholic acid, and creatinine) were screened out. Beneficial bacteria such as Lactobacillus were in positive correlation with butyric acid and urolithin A(P<0.05). The pathogenic bacteria such as Escherichia-Shigella were in negative correlation with propionic acid and urolithin A(P<0.05). In summary, SZD-JF caused obvious intestinal injury to normal rats, which could lead to intestinal flora disorder. The addition of Jujubae Fructus can alleviate the disorder and relieve the injury by regulating intestinal flora and the metabolites. This study discusses the effect of Jujubae Fructus in relieving the intestinal injury caused by SZD and the mechanism from the perspective of intestinal flora-host metabolism, which is expected to serve as a reference for clinical application of this prescription.

Effect of Kansui Radix stir-fried with vinegar on fecal metabolomics in Walker-256 rats with ascites / 中国中药杂志

Utilizing metabolomics technology, this study explored the change of fecal endogenous metabolites in Walker-256 rats with malignant ascites after the administration with Kansui Radix(KR) stir-fried with vinegar(VKR), sought the potential biomarkers in feces which were related to the treatment of malignant ascites by VKR and revealed the biological mechanism of water-expelling effect of VKR. Ultra-fast liquid chromatography-quadrupole-time-of-flight mass spectrometry(UFLC-Q-TOF-MS) was employed to detect the feces of rats in all groups. Principle component analysis(PCA) and partial least squares discriminant analysis(PLS-DA) were conducted to achieve pattern recognition. Combining t-test and variable importance in the projection(VIP) enabled the screening of potential biomarkers for the malignant ascites. Metabolic pathway analysis was accomplished with MetaboAnalyst. Correlation analysis was finally conducted integrating the sequencing data of gut microbiota to elucidate the mechanism underlying the water-expelling effect of VKR. The results showed that both KR and VKR could restore the abnormal metabolism of model rats to some extent, with VKR being inferior to KR in the regulation. Eleven potential biomarkers were identified to be correlated with the malignant ascites and five metabolic pathways were then enriched. Four kinds of gut microbiota were significantly related to the potential biomarkers. The water-expelling effect of VKR may be associated with the regulation of phenylalanine metabolism, biosynthesis of phenylalanine, tyrosine and tryptophan, tryptophan metabolism, glycerophospholipid metabolism, and glycosylphosphatidylinositol(GPI)-anchor biosynthesis. This study can provide a scientific basis for comprehensive understandings of the interaction between gut microbiota and host which has relation to the water-expelling effect of VKR and guide the reasonable clinical application of VKR.

Chemical ingredient groups B and C in Kansui Radix stir-fried with vinegar affect diversity of gut microbiota in rat model of malignant ascites induced by Walker-256 cells / 中国中药杂志

This study aims to explore the effects of chemical ingredient groups B and C in Kansui Radix stir-fried with vinegar on the diversity of gut microbiota in the rat model of malignant ascites, identify the key differential microbial taxa, and reveal the biological mechanism of water-expelling effect of the two chemical ingredient groups. The rat model of malignant ascites induced by Walker-256 cells was established, and phenolphthalein was used as the positive drug. The rats were orally administrated with corresponding agents for consecutive 7 days. On day 6, fresh feces samples were collected from the rats, and 16 S rDNA high-throughput sequencing and GC-MS were employed to determine the composition of gut microbiota and the content of short-chain fatty acids, respectively. On day 7, serum and intestinal tissue samples were collected for the determination of related indicators. Compared with the control group, the model group showed decreased feces volume and urine volume(P<0.01), increased volume of ascites and levels of Na~+, K~+, and Cl~- in urine(P<0.01), down-regulated mRNA and protein levels of intestinal AQP8(P<0.01), lowered abundance of beneficial Lactobacillus(P<0.01) while risen abundance of potential pathogenic Lachnospiraceae and Anaeroplasma(P<0.01), and reduced content of short-chain fatty acids(P<0.01). Compared with the model group, administration with chemical ingredient groups B and C alleviated all the above indicators(P<0.01). In conclusion, chemical ingredient groups B and C in Kansui Radix stir-fried with vinegar could alleviate the disordered gut microbiota in rats with malignant ascites to expel water through increasing the abundance of beneficial Lactobacillus and reducing the abundance of harmful Lachnospiraceae and Anaeroplasma. This study can provide a reference for the reasonable clinical application of Kansui Radix stir-fried with vinegar.

Pharmacokinetic study of anti-human T-cell porcine immunoglobulin combined with cyclosporine A immunosuppressive therapy in patients with severe aplastic anemia / 中华血液学杂志

Objective: To study the metabolic characteristics of anti-human T-cell porcine immunoglobulin (p-ATG) in patients with severe aplastic anemia (SAA) . Methods: For patients with SAA treated with p-ATG combined cyclosporine A (CsA) immunosuppressants between February 2017 and December 2017, the p-ATG dose was 20 mg·kg(-1)·d(-1) over 12 h of intravenous administration for 5 consecutive days. The blood concentration of p-ATG was detected by the three-antibody sandwich ELISA method, the pharmacokinetic analysis software was fitted, and the second-chamber model method was used to calculate the pharmacokinetic parameters and plot the pharmacokinetic curve. Adverse events were recorded and the hematologic reactions were determined at 6 months after treatment. Results: Sixteen patients with SAA treated with p-ATG were enrolled, including 8 females and 8 males, with a median age of 22 years (range, 12 to 49 years) and a median weight of 62.5 kg (range, 37.5 to 82.0 kg) . The pharmacokinetics of p-ATG could be evaluated in 14 cases. p-ATG is distributed in vivo as a two-chamber model, with an average drug concentration peak (T(max)) of (5.786±2.486) days, a peak concentration (C(max)) of (616±452) mg/L, and a half-life of (10.479±8.242) days. The area under the drug time curve (AUC) was (5.807±3.236) mg/L·d. Six months after treatment, 8 of 14 patients received a hematologic response; the AUC (0-t) of the effective group and ineffective groups was (7.50±3.26) mg/L·d vs (4.50±2.18) mg/L·d, and the C(max) was (627±476) mg/L vs (584±382) mg/L, respectively. Conclusion: The plasma concentration of p-ATG reached a peak after 5 days of continuous infusion, and then decreased slowly, with a half-life of 10.479 days, and the residual drug concentration was detected in the body 60 days after administration. A relationship between drug metabolism and efficacy and adverse reactions could not be determined.

Reassessing the six months prognosis of patients with severe or very severe aplastic anemia without hematological responses at three months after immunosuppressive therapy / 中华血液学杂志

Objective: To reassess the predictors for response at 6 months in patients with severe or very severe aplastic anemia (SAA/VSAA) who failed to respond to immunosuppressive therapy (IST) at 3 months. Methods: We retrospectively analyzed the clinical data of 173 patients with SAA/VSAA from 2017 to 2018 who received IST and were classified as nonresponders at 3 months. Univariate and multivariate logistic regression analysis were used to evaluate factors that could predict the response at 6 months. Results: Univariate analysis showed that the 3-month hemoglobin (HGB) level (P=0.017) , platelet (PLT) level (P=0.005) , absolute reticulocyte count (ARC) (P<0.001) , trough cyclosporine concentration (CsA-C0) (P=0.042) , soluble transferrin receptor (sTfR) level (P=0.003) , improved value of reticulocyte count (ARC(△)) (P<0.001) , and improved value of soluble transferrin receptor (sTfR(△)) level (P<0.001) were related to the 6-month response. The results of the multivariate analysis showed that the PLT level (P=0.020) and ARC(△) (P<0.001) were independent prognostic factors for response at 6 months. If the ARC(△) was less than 6.9×10(9)/L, the 6-month hematological response rate was low, regardless of the patient's PLT count. Survival analysis showed that both the 3-year overall survival (OS) [ (80.1±3.9) % vs (97.6±2.6) %, P=0.002] and 3-year event-free survival (EFS) [ (31.4±4.5) % vs (86.5±5.3) %, P<0.001] of the nonresponders at 6 months were significantly lower than those of the response group. Conclusion: Residual hematopoietic indicators at 3 months after IST are prognostic parameters. The improved value of the reticulocyte count could reflect whether the bone marrow hematopoiesis is recovering and the degree of recovery. A second treatment could be performed sooner for patients with a very low ARC(△).

Characteristics of bone marrow compensatory erythropoiesis in hereditary spherocytosis / 中华血液学杂志

Objective: To reveal the compensatory features of bone marrow (BM) erythropoiesis in hereditary spherocytosis (HS) and to explore the effect of diferent hemoglobin levels on this compensation. Methods: Clinical and laboratory data of patients with HS were collected, and the peripheral blood absolute reticulocytes counts value was taken as the surrogate parameter to evaluate the ability of erythropoiesis compensation. BM erythropoiesis compensation in HS with diferent degrees of anemia were evaluated. Results: ①Three hundred and two patients were enrolled, including 115 with compensated hemolytic disease, 74 with mild anemia, 90 with moderate anemia, and 23 with severe anemia. ②Hemoglobin (HGB) was negatively correlated with serum erythropoietin in the decompensated hemolytic anemia group (EPO; rs=-0.585, P<0.001) . ③The median absolute reticulocyte count (ARC) of HS patients was 0.34 (0.27, 0.44) ×10(12)/L, up to 4.25 times that of normal people. The maximum ARC was 0.81×10(12)/L, about 10 times that of normal people. The median ARC of patients with compensated hemolytic disease was 0.29 (0.22, 0.38) ×10(12)/L, up to 3.63 times that of normal people. The median ARC of patients with hemolytic anemia was 0.38 (0.30, 0.46) ×10(12)/L, which was significantly higher than the patients with compensated hemolytic disease, up to 4.75 times that of normal people (z=4.999, P=0.003) . ④ ARC was negatively correlated with HGB in the compensated hemolytic disease group (rs=-0.177, P=0.002) and positively correlated with HGB in the decompensated hemolytic anemia group (rs=0.191, P=0.009) . There was no significant difference in the ARC among patients with mild, moderate, and severe anemia (χ(2)=4.588, P=0.101) . ⑤The median immature reticulocyte production index of the mild, moderate, and severe anemia groups was 13.1% (9.1%, 18.4%) , 17.0% (13.4%, 20.8%) , and 17.8% (14.6%, 21.8%) , respectively; the mild anemia group had lower index values than the moderate and severe anemia groups (P(adj) values were both<0.05) , but there was no significant difference between the latter groups (P(adj)=1.000) . The median immature reticulocyte count of patients in the mild, moderate, and severe groups was 5.09 (2.60, 7.74) ×10(10)/L, 6.24 (4.34, 8.83) ×10(10)/L, and 7.00 (3.07, 8.22) ×10(10)/L, respectively; there was no significant difference among the groups (χ(2)=3.081, P=0.214) . Conclusion: HGB can be maintained at a normal level through bone marrow erythropoiesis, while red blood cells are reduced in HS. However, once anemia develops, the bone marrow exerts its maximum erythropoiesis capacity and does not increase, regardless of anemia aggravation or serum EPO increase.

Relationship between Changes of Lymphocyte Subsets and Early Hematologic Response in Immunosuppressive Therapy of Severe Aplastic Anemia Patients / 中国实验血液学杂志

OBJECTIVE@#To explore the relationship between the change of lymphocyte subsets before and after immunosuppressive therapy (IST) with disease severity of severe aplastic anemia (SAA) and hematologic response to IST.@*METHODS@#The clinical data of 94 patients with SAA/VSAA treated by r-ATG and CsA in our hospital from December 2009 to October 2011 was analyzed retrospectively. Among them, 26 patients who had sequential data of lymphocyte subsets and cytokines before and after treatment were enrolled. The relationship between lymphocyte subsets, cytokine level before IST and disease severity, as well as the relationship between changes if lymphocyte subsets, changes of cytokine and the HR after IST for 6 months was analyzed.@*RESULTS@#There were no statistical differences in the ratio and absolute count of lymphocyte, the ratio and absolute count of each lymphocyte subsets, including CD3@*CONCLUSION@#The hematopoietic recovery and early hematologic remission may be affected by the intensity of immune suppression reflected from the changes of lymphocyte subsets and the immune reconstruction reflected from the recovery of lymphocyte subsets. The immune reconstruction is most significant within 3 months after IST.

Endometrial Injury and Preservation after Magnetic Resonance-guided Focused Ultrasound Ablation of Uterine Fibroids / 中国医学科学院学报

Objective To explore the risk factors for incident endometrial injury and 3-month endometrial injury after magnetic resonance-guided focused ultrasound(MRgFUS)ablation of uterine fibroids(UF). Methods UF patients who were diagnosed in Peking Union Medical College Hospital and underwent MRgFUS ablation in Amcare Women's and Children's Hospital from August 2016 to October 2020 were retrospectively enrolled in this study.Clinical data of 66 UF patients were collected and compared between endometrial injury group and non-injury group.Stepwise regression was employed to determine the risk factors for the incident endometrial injury and 3-month endometrial injury.Multivariate logistic regression analysis was performed to explore the relationship of endometrial injury with age,pre-ablation tumor size,multiple UF,International Federation of Gynecology and Obstetrics(FIGO)classification,T2WI signal intensity,and treatment time.Results In terms of incident endometrial injury,the 66 patients included 41(62.1%)cases with no injury,4 cases(6.1%) with grade 1 injury,5 cases(7.6%)with grade 2 injury,and 16 cases(24.2%)with grade 3 injury.In terms of 3-month endometrial injury,the 66 patients included 49 cases(74.2%)with no injury,5 cases(7.6%)with grade 1 injury,2 cases(3.0%)with grade 2 injury,and 10 cases(15.2%)with grade 3 injury.Stepwise regression analysis indicated that FIGO classification was significantly associated with incident endometrial injury(

Predictive Value of Texture Analysis in the Treatment of Magnetic Resonance-guided Focused Ultrasound Surgery for Symptomatic Uterine Fibroids / 中国医学科学院学报

Objective To evaluate the predictive value of texture analysis in the treatment of magnetic resonance-guided focused ultrasound surgery(MRgFUS)for symptomatic uterine fibroids.Methods Totally 16 patients with symptomatic uterine fibroids who accepted MRgFUS in Peking Union Medical College Hospital from April 2010 to January 2013 were included. Enhanced magnetic resonance imaging(MRI)was performed before treatment,immediately after treatment,and during the 12-month follow-up. The TexRAD software was used to measure the texture parameters of the fibroids in T2WI sagittal images,and the texture indicators including means and standard deviations(SD),entropy,mean of positive pixels(MPP),skewness,and kurtosis were collected. The fibroid's volume and their change rates were calculated by measuring the relevant diameter of the target fibroid. The Uterine Fibroid Symptoms and Quality of Life(UFS-QOL)was used to calculate the symptom severity scores(SSS)and its change rate. The statistical difference of parameters among the groups was analyzed. The correlations between each texture parameter and the therapeutic outcome of the fibroids were analyzed respectively.Results The average volume for fibroids before treatment was(96.5±84.9)cm ,which was reduced to(55.1±71.0)cm after treatment for 12 months,and the volume change rate(εV%)was(49±20)%. The standardized SSS score before treatment was(34.18±15.29)scores,decreased to(17.78±11.84)scores 12 months after treatment,with a change rate of(45±32)%,and the non-perfused volume ratio(NPV%)was(62±20)%. There were significant differences among the parameters mean,SD,entropy,and MPP among three groups(all P<0.05),and the changes of them were regular,all of which showed a significant decrease immediately after treatment and a significant increase 12 months after treatment,and the increase degree was higher than the preoperative level. SD(SSF2:r=0.503,P=0.047;SSF4:r=0.529,P=0.035;SSF6:r=0.519,P=0.039)and entropy(SSF2:r=0.527,P=0.036;SSF4:r=0.517,P=0.040;SSF6:r=0.495,P=0.050)of the after-treatment group moderately associated with the εV%. Entropy of the before-treatment group was moderately associated with NPV%(SSF2:r=0.507,P=0.045;SSF4:r=0.543,P=0.030;SSF6:r=0.548,P=0.028).Conclusion There is a certain correlation between the changes of MRI texture parameters before and after treatment and the effect of MRgFUS in the treatment of uterine fibroids,and texture analysis may have certain value in the predicting the effect of MRgFUS on uterine fibroids.

The clinical and laboratory characteristics of congenital pyruvate kinase deficiency / 中华内科杂志

Clinical data of 19 patients with congenital pyruvate kinase deficiency were analyzed. Insufficient pyruvate kinase confirmed the diagnosis. Laboratory parameters of hemolysis were summarized. In cases of neonatal hyperbilirubinemia and unexplained hemolytic anemia, pyruvate kinase activity and next generation sequencing test may help the early diagnosis.

Treating glioma with umbilical cord mesenchymal stem cells: mechanism of action, safety and future application / 中国组织工程研究

BACKGROUND: Umbilical cord mesenchymal stem cells (UC-MSCs) are a group of cells that have self-renewal, highly proliferative and multidrug differentiation potential. The properties of UC-MSCs and their tumor tropism make them an ideal tool for glioma cell therapy. These cells can act by paracrine or as a delivery system for genes and drugs. It has been demonstrated that UC-MSCs can inhibit the growth of glioma and improve the survival after transplantation into the brain. OBJECTIVE: To summarize the molecular mechanisms and safety of UC-MSCs in the treatment of glioma and to provide a useful reference for further research. METHODS: We searched the PubMed and CNKI databases from 2000 to 2017 with the English terms of "glioma; umbilical cord mesenchymal stem cells" and the Chinese terms of "glioma; umbilical cord mesenchymal stem cells; safety; molecular mechanism". Based on the inclusion and exclusion criteria, 55 articles were finally reserved for review. RESULTS AND CONCLUSION: UC-MSCs have obvious effect on treating glioma. These cells can treat glioma through homing mechanism and paracrine mechanism as gene carrier and co-culture. Moreover, UC-MSCs have certain safety in the treatment of glioma.

The characteristic of hereditary spherocytosis related gene mutation in 37 Chinese hereditary spherocytisis patients / 中华血液学杂志

Objective@#To reveal the genetic characteristics of erythrocyte membrane protein in hereditary spherocytosis (HS) in China.@*Methods@#Next-generation sequencing technology was used to detect mutations in genes of erythrocyte membrane proteins in 51 clinically diagnosed HS patients. The relationship between gene mutations and clinical phenotypes was analyzed.@*Results@#Mutations in erythrocyte membrane protein genes were detected in 37 patients, including 17 with ANK1 mutations (17/37, 45.9%), 14 with SPTB mutations (14/37, 37.8%), and 5 with SLC4A1 mutations (5/37, 13.5%). One patient carried both heterozygous ANK1 mutation and SPTB mutation (1/37, 2.7%). SPTA1 and EPB42 mutation was not fou nd in any patient. Nonsense mutations (36.8%) and missense mutations (31.6%) were most common. Of the 38 mutations detected, 34 were novel mutations and have not been reported elsewhere (89.5%). Sixteen HS patients underwent parental genetic validation, 6 patients (37.5%) inherited gene mutation from parents and 10 (62.5%) were de novo. The peripheral blood cell parameters of HS patients were not related to the mutant genes and gene mutation types. However, it seems that HS patients with mild clinical status are prone to carry SPTB mutations while more patients with severe clinical status have ANK1 mutations.@*Conclusions@#ANK1 and SPTB are the most common mutant genes in Chinese HS patients, mainly with missense mutations and nonsense mutations. There was no significant correlation between the mutation of HS related genes and the severity of HS.

Using target next-generation sequencing assay in diagnosing of 46 patients with suspected congenital anemias / 中华血液学杂志

Objective@#To evaluate the impact of the targeted next-generation sequencing (NGS) assay for difficult congenital anemias.@*Methods@#Blood Disease Hospital Anemia Panel 2014 (BDHAP-2014) including 217 known genes of congenital anemias was developed. NGS and parental verification were performed for patients who were suspected diagnosed with congenital anaemia from August 2014 to July 2017.@*Results@#A total of 46 patients were enrolled in this study, the clinical suspection were 11 cases Fanconi anemia (FA), 8 cases congenital dyserythropoietic anemia (CDA), 6 cases congenital sideroblast anemia (CSA), 12 cases congenital hemolytic anemia (CHA), 1 case dyskeratosis congenital (DC), 4 cases iron-refractory iron deficiency anemia and 4 cases unexplained cytopenia (Uc), respectively. 28 (60.9%) of 46 patients became confirmed cases after targeted NGS, corresponding to 44 mutations of which 33 were new. 26(56.5%) patients with results of the assay matching to clinical suspection, including FA (5/11, 45.5%), CSA (6/6, 100.0%), CDA (3/8, 37.5%) and CHA (12/12, 100.0%). 2 (4.3%) cases not matching to clinical suspection, including dyskeratosis congenital (DC) was made in 1(2.2%) patients with suspected FA and familial hemophagocytic lymphohistiocytosis (FHL) was made in 1(2.2%) patients with suspected unexplained cytopenia (Uc). In 12 CHA patients, the hemolytic type was further clarified by the NGS. The remaining 18 cases were not clearly diagnosed.@*Conclusion@#Targeted NGS assay is of major impact on congenital anemias. The assay should be used routinely in congenital anemias.

The life span of red blood cell in patients with severe/very severe aplastic anemia / 中华血液学杂志

Objective@#To explore the life span of red blood cells (RBC) in patients with severe/very severe aplastic anemia (SAA/VSAA).@*Methods@#Clinical data of 128 SAA/VSAA patients from November 2016 to April 2017 were retrospectively analyzed, and 13 healthy volunteers in the same period was used as normal control. The endogenous Breath Carbon Monoxide (CO) test was used to detect the life span of RBC in SAA/VSAA patients, and the effect of immunosuppressive therapy (IST) on the life span of RBC in these patients was explored.@*Results@#The mean life span of RBC in 51 untreated SAA/VSAA patients was (50.69±21.43) d, which was significantly shorter than that in normal controls[(111.85±31.55) d](t=-6.611, P<0.001). The mean life span of RBC in 77 patients treated with IST was (87.14±39.28) d. The mean life span of RBC in complete responses (CR), hematologic response (HR) and non-response (NR) patients were (106.15±32.12) d, (92.00±38.60) d and (50.44±21.56) d, respectively. The life span of RBC in patients with HR was significantly longer than that in newly diagnosed and NR patients (t=7.430, P<0.001; t=4.846, P=0.002), which was similar to that in the normal controls (t=-1.743,P=0.085). There was no statistical significance between CR patients and the normal controls in the mean life span of RBC (t=-0.558, P=0.579). No factor affecting the RBC life span was found in univariate logistical regression analyses in the newly diagnosed SAA/VSAA patients. The serum levels of IL-2R and IL-6 were much lower in HR patients than NR patients[IL-2R: 4.3×105 U/L vs 6.5×105 U/L, z=-2.733, P=0.006; IL-6: 2.6 (2.0-17.7) ng/L vs 6.1 (2.0-14.4) ng/L, z=-2.968, P=0.003]. Of the 51 newly diagnosed patients, 38 received IST and their 3-month curative effect was evaluated. Receiver operator characteristics (ROC) curve was used to analyze the predictive effect of RBC life span of untreated patients on the efficacy of IST before treatment. The cut-off point was 60 days with sensitivity of 37.5% and specificity of 86.4%. In 9 cases with life span of RBC>60 d before IST, 6 cases acquired HR, while in 29 cases with life span of RBC ≤ 60 d before IST, 10 cases acquired HR, the difference was not statistically significant (P=0.128).@*Conclusion@#The life span of RBC in SAA/VSAA patients was shortened, which can be improved even recovered to the normal after IST. Elevated cytokines might play a role in the pathophysiology of the shortened RBC life span in SAA/VSAA.

Experience of YU Yun in Treating Primary Carcinoma of Liver by Using Acupuncture after Pulse Diagnosis / 中国中医药信息杂志

This article introduced the experience of Professor YU Yun in treating the primary carcinoma of liver by using acupuncture after pulse diagnosis. Professor YU thinks that the overall pathogenesis of liver cancer is deficiency of zang-fu organs, so the cancer cells can invade and occupy in the liver. Therefore, Professor YU uses the way of supporting the healthy qi and driving out the cancer as the treatment principle from multiple organs and meridians. On the basis of the theories of Nei Jing, Professor YU creates the acupuncture after pulse diagnosis. He feels the pulse on the basis of four pulses: Cunkou, Renying, Chongyang, and Taixi. According to the feelings of the pulses, he compares the size and speed, strong or weak, smooth or nonfluency of the four pulses. In treatment, he uses reducing method when the pulse is strong and fast, and tonic method when the pulse is weak and slow. He chooses the main acupuncture points on head, face, belly, flank and lower limbs. According to the experience, Professor YU uses gold needle in tonic method and uses silver needle in reducing method. In this way, the acupuncture after pulse diagnosis can regulate zang-fu organs and meridians, yin and yang, qi and blood, and promote blood circulation for removing blood stasis and resolving dampness, and attack the retained fluid and tumour in the liver, and combined with adjunct points to treat cancer.

Application value of ultrasound examination for evaluating knee joint status in patients with hemophilia / 重庆医学

Objective To study the application value of ultrasound(US) examination for evaluating the knee joint status in the patients with hemophilia.Methods The US examination data of 44 patients (70 knee joints) with hemophilia were collected,among them 11 cases aged below 18 years old,16 knee joints completed the MRI examination,meanwhile the knee joint health status was evaluated by adopting the 2.1 version of hemophilia joint health assessment (HJHS) form.Then the correlation between the US score with the age and bleeding times and the relation between MRI score with HJHS score were analyzed.Results The severity of hemophilia arthropathy had no obvious correlation with hemophilia severity (F=0.013,P =0.987).With the age increase and bleeding frequency increase,the knee joint lesion was aggravated.The detection of early synovial thickening and cartilage change in arthropathy had no obvious difference between US and MRI examinations(P＞0.05);the obvious correlation existed among US score,MRI score and HJHS (P＜0.05).Conclusion US has an important significance for the early diagnosis of hemophilic arthropathy.

A study on the effect of Cucurbitacin B on the inflammatory reaction of murine alveolar macrophages induced by lipopolysaccharide / 预防医学

Objective To investigate the anti-inflammatory effect of Cucurbitacin B on the inflammatory reaction of murine alveolar macrophages induced by lipopolysaccharide and its molecular mechanism. Methods The alveolar macrophages were randomly divided into five groups: blank group, LPS group, different concentrations of Cucurbitacin B (1μM, 2.5μM, 5μM)+) +LPS groups. All group cells were pretreated with different concentrations for 2 h, and followed by 1μg/mL LPS. The protein level of TNF-α, IL-1β, IL-6 and PGE2 were detected by ELISA assay, and the NO was detected by Griess methods, and its upstream protein i-NOS,COX-2, Nrf2 and HO-1 were detected by Western-blot. Results The secretion of TNF-α, IL-1β, IL-6 and PGE2 in LPS group were increased significantly than blank groups, while Cucurbitacin B suppressed its protein level inadose-dependent manner. The nuclear erythroid related factor 2 and antioxidant gene were activated while Cucurbitacin B was added into alveolar macrophages in adose-dependent manner. Conclusion Cucurbitacin B can inhibit the extracellar secretion of inflammatory cytokines production, and its molecular mechanism could be due to the promoting Nrf2 translocation to the nucleus, activating the expression of HO-1 gene, reducing the expression of iNOS and COX-2, and thereby alleviating the inflammatory reaction.