Fecal microbiota transplantation in obesity metabolism: A meta analysis and systematic review.

OBJECTIVE: The effect of fecal microbiota transplantation (FMT) on microbiota engraftment in patients with metabolic syndrome remains unclear. This systematic review employed a meta-analysis of RCTs for assessment on the role of FMT in treating obesity and metabolic syndrome, and its impact on clinically relevant parameters. METHOD: Major databases and grey literatures were searched identifying RCTs comparing FMT of lean donors with placebo in obese/metabolic syndrome patients. Studies using any form of placebo were included. Variations in the parameters before and after treatment were calculated followed by meta-analyses. RESULT: Ten studies met the inclusion criteria and a total of 334 patients were included for further analysis. Clinically significant parameters associated with obesity and metabolic syndrome were explored and FMT was identified significantly and negatively associated with most indices of abdominal adiposity including caloric intake, fasting glucose, HOMA-IR, systolic blood pressure, diastolic blood pressure, total cholesterol, HDL, LDL, triglycerides and CRP, Obesity parameters including fasting glucose and acetic acid were increased following FMT. CONCLUSION: FMT is more advantageous for obese patients with elevated blood pressure, disordered glucose and insulin metabolism, and elevated blood lipids. The study of metabolic factors in obese patients will be our starting point in the future.

Progress on internal exposure to typical environmental persistent organic pollutants and cancer / 环境与职业医学

Environmental pollution is closely linked to the occurrence and development of cancer. Chemical carcinogens are the most important environmental factors causing cancer in humans. Among them, persistent organic pollutants (POPs) are characterized by their widespread distribution, persistence, and bioaccumulation. Research on the carcinogenic effects of POPs has received considerable attention in recent years. This article reviewed the internal exposure, association with cancer risk, and potential carcinogenic mechanisms of five typical classes of POPs in the environment, including polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), per- and poly-fluoroalkyl substances (PFAS), brominated flame retardants (BFRs), and short-chain chlorinated paraffins (SCCPs). These five types of POPs have distinct carcinogenic mechanisms, including interfering with cell proliferation cycle, altering epigenetic inheritance, promoting oxidative stress, altering energy metabolism, and affecting immune function. The development of cancer is the result of interaction between intrinsic genetic factors and external environmental factors. In addition to focusing on how environmental POPs affect the genetic material of organisms, it is also important to consider their effects on the tumor microenvironment, including tumor immunity and angiogenesis. Understanding these effects is crucial for guiding future efforts in pollution control and precision medicine in cancer treatment.

Prognosis of childhood adrenoleukodystrophy with cognitive disorder after haploidentical allogenic hemato-poietic stem cell transplantation / 中华实用儿科临床杂志

Objective:To investigate the prognosis of childhood adrenoleukodystrophy (ALD) with cognitive disorder after haploidentical allogenic hematopoietic stem cell transplantation (haplo-HSCT), and to identify risk factors affecting the prognosis.Methods:It was a single-center retrospective study involving 31 ALD children receiving haplo-HSCT in Peking University People′s Hospital from January 2014 to October 2022.Survival analysis was performed by Kaplan-Meier method. Cox regression analysis was performed to identify risk factors for the prognosis of childhood ALD following haplo-HSCT. Results:Among the 31 children with ALD, 1 case died of cardiogenic shock during the transplantation, and the remaining had a successful haplo-HSCT.Ten children with ALD had cognitive disorder before haplo-HSCT, including 3 cases with the minimal LOES score ≥10 points and 8 cases with the Neurologic Function Score (NFS)>0 point before haplo-HSCT.Six children had major functional disability (MFD) and 2 cases died due to progression of ALD after haplo-HSCT.Twenty children did not have cognitive disorder before haplo-HSCT, of whom 3 cases had the LOES score≥10 points and 6 cases had NFS>0 before haplo-HSCT.Four children had MFD and 2 cases died due to progression of ALD after haplo-HSCT.For ALD patients without cognitive disorder after haplo-HSCT, the 3-year and 5-year survival rate were 100.0% and 72.9%, respectively, and the 5-year MFD-free survival was 61.6%.For ALD patients with cognitive disorder after haplo-HSCT, the 3-year survival rate was 83.3%.Compared with ALD patients with the LOES score<10 points before haplo-HSCT, those with the LOES score≥10 points had 9.243 times the risk of developing MFD after haplo-HSCT ( P=0.024, 95% CI: 1.332-64.127). Compared with ALD patients without cognitive disorder before haplo-HSCT, ALD patients with cognitive disorder had 9.749 times the risk of developing MFD after haplo-HSCT ( P=0.023, 95% CI: 1.358-66.148). Conclusions:Cognitive disorder and LOES score≥10 points before haplo-HSCT are risk factors for developing MFD in children with ALD following haplo-HSCT.

Regulatory Effect of Wenyang Prescription， Jieyu Prescription， and Wenyang Jieyu Prescription on Pain Sensitivity and Depression-like Behaviors in Mice Induced by Maternal Separation and Chronic Neuropathic Pain / 中国实验方剂学杂志

ObjectiveTo observe the behavioral and pain threshold alterations， as well as the changes in indexes related to depression and pain in the serum and central system in mice stressed by maternal separation and chronic neuropathic pain， and explore the underlying mechanism of Wenyang prescription （WY）， Jieyu prescription （JY）， and Wenyang Jieyu prescription （WYJY） in improving depression and pain sensitivity. MethodThe birth date of mice was recorded as PD0. After birth， the mice were divided into a blank group and an experimental group. The neonatal mice in the experimental group underwent maternal separation in PD5-14 at 8 h·d-1. After ablactation， the mice were divided into a maternal separation group， a WY group （Erxian decoction， 5.84 g·kg-1）， a JY group （Xiaoyaosan， 12.00 g·kg-1）， a WYJY group （16.68 g·kg-1）， and a fluoxetine group （2.60 mg·kg-1）， with 15 mice in each group. Meanwhile， 15 male mice of the same age without maternal separation were assigned to the normal control group. Mice in the blank group and the maternal separation group were fed on a regular chow diet in PD21-PD90， while the remaining groups were fed on the corresponding drugs. In PD91， sciatic nerve ligation was performed to induce a model of maternal separation and chronic neuropathic pain. The open field test was used to observe the depression-like behaviors of mice in each group， and the mechanical and temperature pain thresholds were measured to detect the pain sensitivity of mice in each group. The serum levels of corticosterone （CORT）， substance P， and β-endorphin （β-EP） were determined by enzyme-linked immunosorbent assay （ELISA）， and the expression of the glucocorticoid receptor （GR） in the amygdala and β-EP protein in the hypothalamus was detected by immunohistochemistry. The mRNA expression levels of amygdala GR gene （Nr3c1）， FK506 binding protein 5 gene （FKBP5）， metabolic glutamate receptor 5 gene （GRM5）， and brain-derived neurotrophic factor （BDNF） were detected by real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）. ResultCompared with the blank group， the maternal separation group showed reduced stay time and total distance traveled in the 5-min open field test （P<0.01）， reduced mechanical pain threshold （P<0.01）， increased serum CORT and β-EP （P<0.01）， declining FKBP5 mRNA expression （P<0.01）， and increased hypothalamic β-EP expression （P<0.05）. Compared with the maternal separation group， the groups with drug intervention showed prolonged stay time （P<0.05， P<0.01） and up-regulated pain thresholds to different degrees. The total distance traveled in the 5-min open field test increased in the WY group， the WYJY group， and the fluoxetine group （P<0.05， P<0.01）. The JY group showed decreased serum CORT （P<0.01）， reduced β-EP ， and increased BDNF mRNA （P<0.01）. Nr3c1 and GRM5 mRNA decreased in the WY group （P<0.05， P<0.01）. The WYJY group showed decreased serum CORT （P<0.05）and decreased Nr3c1， GRM5， and BDNF mRNA （P<0.05， P<0.01）. The levels of β-EP expression were elevated to different degrees in the groups with drug intervention， but the differences were not significant. The levels of GR expression in the WY group， the JY group， and the WYJY group increased （P<0.05）. ConclusionWYJY can inhibit central pain sensitization and regulate hypothalamic-pituitary-adrenal gland （HPA） axis function by enhancing the expression of GR in the amygdala and inhibiting neuroplasticity and excitability in the amygdala to relieve depression-like behaviors and improve somatic hyperalgesia.

Establishment of a system for rapid detection of JAK2 V617F mutation in myeloproliferative diseases / 中华医学遗传学杂志

Objective@#To develop a system for rapid detection of JAK2 V617F mutation among patients with myeloproliferative diseases.@*Methods@#Specific primers and TagMan probes were designed for the mutant and wild type alleles based on the principle of real-time PCR. A complete system including the method for detection and product for quality control were established through the evaluation of sensitivity and accuracy of the method, double-blind trial, and preparation of negative and positive controls through site-directed mutagenesis and molecular cloning.@*Results@#A system for rapid detection of the JAK V617F mutation has been developed. Compared with Sanger sequencing, the sensitivity and specificity of the method have both reached 100%. Meanwhile, 1000 normal samples and 1 case with the JAK2 V617F mutation were detected, which gave a population rate of 1‰.@*Conclusion@#The system was fast, accurate, cheap, high throughput, and easy to use. It can be utilized as a routine test. Although the JAK2 V617F mutation is rare in the population, it should be screened among myeloproliferative neoplasm patients.

Clinical application of neutrophil-to-lymphocyte ratio in predicting the prognosis of H7N9 avian influenza / 中华传染病杂志

Objective To explore the predictive value of neutrophil-to-lymphocyte ratio on the prognosis of H7N9 avian influenza.Methods A retrospective analysis was conducted on 28 H7N9 avian influenza patients (treatment group) at the First Affiliated Hospital of Soochow University from April 2013 to January 2016.Thirty healthy physical examiners in the same period were enrolled as the healthy control group.The 28 patients were followed up for half a year and divided into the improvement group (18 cases) and the death group (10 cases) according to the clinical prognosis.Inflammatory indicators including white blood cells (WBC),neutrophil (N),lymphocyte (L),monocytes (M),platelet (PLT),creatine kinase (CK),lactate dehydrogenase (LDH),high sensitive C reactive protein were collected at day 1,day 3 and week 1 of admission.Calculation of neutrophil-to-lymphocyte ratio (NLR),platelet-to-lymphocyte ratio (PLR),lymphocyte-to-monocyte ratio (LMR),△NLR3 (day 3 of admission NLR-on day 1 of admission NLR),△NLR7 (week 1 of admission NLR-day 3 of admission NLR) and so on calculating △PLR3,△PLR7,△LMR3,△LMR7.Differences of the above indicators between the improvement group and death group were compared.The measurement data with normal distribution were tested by t-test of two independent samples,and the count data with non-normal distribution were tested by Mann-Whitney U-test.Univariate and multivariate logistic regression analysis to explore the prognostic factors and the working characteristic curve of subjects was used to evaluate the predictive value of inflammatory response indexes for H7N9 avian influenza death.Results In the treatment group,the baseline WBC,L,N,PLT,the proportion of lymphocytes,neutrophils,monocytes,and NLR,PLR,and LMR were all statistically different compared with the healthy control group (all P ＜0.01).After treatment,day 3 NLR,△NLR3 in improvement group were both significantly decreased to 10.93 (15.71)and0.87 (-15.63),respectively when compared with death group (17.62[23.63] and 7.42[22.68],respectively) (Z =-2.16 and-2.014,respectively,both P＜0.05).Day 7 NLR,△NLR7 in improved group were 6.51 (13.23) and-0.37 (-12.38),respectively,which were both lower than those of death group (27.90 [25.64] and 11.54 [-26.22]) with statistically significant differences (Z =-2.444 and -2.111,respectively,both P ＜ 0.05).Multivariate logistic regression analysis indicates that △NLR3 is the main factor that affects the prognosis of the H7N9 infection (odds ratio [OR] =1.153,95％ confidence interval [CI]:1.052-1.263,P =0.002).Reciver operating characteristic curve analysis showed that the area under the curve was 0.733 (95 ％ CI:0.532-0.935,P =0.044).Based on the principle of Youden index,the cutoff value of △NLR3 to predict the death risk of H7N9 avian influenza was 5.453 with sensitivity of 0.700 and the specificity of 0.722.The mortality was higher when △NLR3 was higher than 5.453.Conclusions Dynamic monitoring NLR,especially △NLR3 may reflect the condition and prognosis of H7N9 infection,which is an independent predictor of death.

Establishment of a system for rapid detection of JAK2 V617F mutation in myeloproliferative diseases / 中华医学遗传学杂志

OBJECTIVE@#To develop a system for rapid detection of JAK2 V617F mutation among patients with myeloproliferative diseases.@*METHODS@#Specific primers and TagMan probes were designed for the mutant and wild type alleles based on the principle of real-time PCR. A complete system including the method for detection and product for quality control were established through the evaluation of sensitivity and accuracy of the method, double-blind trial, and preparation of negative and positive controls through site-directed mutagenesis and molecular cloning.@*RESULTS@#A system for rapid detection of the JAK V617F mutation has been developed. Compared with Sanger sequencing, the sensitivity and specificity of the method have both reached 100%. Meanwhile, 1000 normal samples and 1 case with the JAK2 V617F mutation were detected, which gave a population rate of 1‰.@*CONCLUSION@#The system was fast, accurate, cheap, high throughput, and easy to use. It can be utilized as a routine test. Although the JAK2 V617F mutation is rare in the population, it should be screened among myeloproliferative neoplasm patients.

Genetic and phenotypic analysis of a rare case with homozygous Chinese Gγ (Aγδβ)-thal deletion / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze the genotype of a patient suspected for thalassemia through a series of experiments.</p><p><b>METHODS</b>Conventional methods for detecting common thalassemia mutations was used in conjunction with multiplex ligation-dependent probe amplification (MLPA) in order to determine the genotype of the patient. Corresponding primers were designed for developing a Gap-PCR system for detecting rare type mutations.</p><p><b>RESULTS</b>The patient was identified as a homozygote for Chinese Gγ(Aγδβ)-thal deletion, with clinical manifestations tending to be intermediate or severe based on the hematological characteristics. A Gap-PCR system has been developed for detecting the above mutation with accuracy and rapidity.</p><p><b>CONCLUSION</b>The Chinese Gγ(Aγδβ)-thal is prevalent in southern China, and caution should be taken to avoid misdiagnosis. The Gap-PCR system for detecting Chinese Gγ(Aγδβ)-thal is suitable for extended applications for its simplicity and rapidity.</p>

Non-invasive prenatal diagnosis for beta-thalassemia by detecting paternal CD41-42 mutation in cell-free DNA derived from maternal plasma with droplet digital PCR / 中华医学遗传学杂志

OBJECTIVE@#To establish a non-invasive method for beta-thalassemia by detecting parental CD41-42 mutation in cell-free DNA derived from maternal plasma with droplet digital PCR (ddPCR).@*METHODS@#Beta-actin gene and beta-thalassemia gene CD41-42 mutation were respectively set as the reference and target sequences. A novel method was established based on Bio-Rad ddPCR technique with specific primers and TaqMan probes for the two genes. The accuracy, sensitivity and detective linearity range of the developed method were evaluated by detection of the target gene gradient concentration samples. The applicability was also evaluated by testing 20 maternal plasma samples.@*RESULTS@#The ddPCR method could accurately detect the beta-thalassemia CD41-42 mutation in cell-free DNA derived from maternal plasma. Within the target sequence concentration ratio of 5.00%-0.50%, the relative errors were all < 0.05, the linear regression equation was Y=1.0101-X-0.0071 and R=0.9994. The results of 20 maternal plasma cell-free DNA samples were all consistent with those of the follow-up testing.@*CONCLUSION@#A ddPCR method for detecting parental CD41-42 mutation in cell-free DNA from maternal plasma was developed. The method is simple, rapid, accurate, and can be applied for non-invasive prenatal diagnosis for couples simultaneously carrying the CD41-42 mutation.

Mechanism of BH3 mimetics promoting cell apoptosis and its latest clinical research progress / 中国药理学与毒理学杂志

Targeting cell apoptosis is currently the most promising therapy for cancer treatment. The BH3-only protein, which is a member of Bcl-2 family, can bind to the pro-survival members of the family and neutralize their functional activities to induce apoptosis (ie, to isolate pro-apoptotic members of the Bcl-2 family). BH3 mimetics, a kind of small molecule compounds, has the ability to mimic the BH3-only protein to induce apoptosis. The prototype of BH3 mimetics is ABT-737, who can selectively targets on BCL-XL, BCL-2 and BCL-W (but not MCL-1 and A1). ABT-263, a derivative of ABT-737, has a better performance of inducing apoptosis and inhibiting the growth of tumor in clinical trials. At this stage, some presumably BH3 mimetics has entered the clinical stage, while a large part of them is still being characterized and tested. Basing on the mechanism of BH3-only protein, this review summarize a variety of BH3 mimetics which have been widely recognized, and show the latest developments of newly diagnosed BH3 mimetics in the field.