Characterization of candidate factors associated with the metastasis and progression of high-grade serous ovarian cancer / 中华医学杂志(英文版)

BACKGROUND@#High-grade serous ovarian cancer (HGSOC) is the biggest cause of gynecological cancer-related mortality because of its extremely metastatic nature. This study aimed to explore and evaluate the characteristics of candidate factors associated with the metastasis and progression of HGSOC.@*METHODS@#Transcriptomic data of HGSOC patients' samples collected from primary tumors and matched omental metastatic tumors were obtained from three independent studies in the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were selected to evaluate the effects on the prognosis and progression of ovarian cancer using data from The Cancer Genome Atlas (TCGA) database. Hub genes' immune landscapes were estimated by the Tumor Immune Estimation Resource (TIMER) database. Finally, using 25 HGSOC patients' cancer tissues and 10 normal fallopian tube tissues, immunohistochemistry (IHC) was performed to quantify the expression levels of hub genes associated with International Federation of Gynecology and Obstetrics (FIGO) stages.@*RESULTS@#Fourteen DEGs, ADIPOQ , ALPK2 , BARX1 , CD37 , CNR2 , COL5A3 , FABP4 , FAP , GPR68 , ITGBL1 , MOXD1 , PODNL1 , SFRP2 , and TRAF3IP3 , were upregulated in metastatic tumors in every database while CADPS , GATA4 , STAR , and TSPAN8 were downregulated. ALPK2 , FAP , SFRP2 , GATA4 , STAR , and TSPAN8 were selected as hub genes significantly associated with survival and recurrence. All hub genes were correlated with tumor microenvironment infiltration, especially cancer-associated fibroblasts and natural killer (NK) cells. Furthermore, the expression of FAP and SFRP2 was positively correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage, and their increased protein expression levels in metastatic samples compared with primary tumor samples and normal tissues were confirmed by IHC ( P = 0.0002 and P = 0.0001, respectively).@*CONCLUSIONS@#This study describes screening for DEGs in HGSOC primary tumors and matched metastasis tumors using integrated bioinformatics analyses. We identified six hub genes that were correlated with the progression of HGSOC, particularly FAP and SFRP2 , which might provide effective targets to predict prognosis and provide novel insights into individual therapeutic strategies for HGSOC.

Leukemia Genotype Analysis of Children with Acute Lymphoblastic Leukemia in Yunnan Area / 中国实验血液学杂志

OBJECTIVE@#To analyze 43 leukemia genes in children with acute lymphoblastic leukemia (ALL) in Yunnan province, and provide the basis for the diagnosis and treatment of children with ALL in this area.@*METHODS@#The clinical data of 428 children with newly diagnosed ALL in Yunnan area from January 2015 to December 2020 were retrospectively analyzed. Multiple nested PCR technology was used to detect 43 common leukemia genes.@*RESULTS@#Among the 428 children with ALL, 159 were positive for leukemia genes, with a positive rate of 37.15% (159/428), and a total of 15 leukemia genes were detected. Among the 159 leukemia gene-positive children, ETV6-RUNX1+ accounted for 25.79% (41/159), followed by E2A-PBX1+ and BCR-ABL+, accounting for 24.53% (39/159) and 23.27% (37/159) respectively. MLL+ accounted for 6.29% (10/159), WT1+ accounted for 4.40% (7/159), IKZF1 gene deletion and CRLF2+ accounted for 3.77% (6/159) respectively. The positive rate of MLL (46.15%) was the highest in ＜1-year old group, the positive rate of ETV6-RUNX1 (10.56%) was the highest in 1-10-year old group, and BCR-ABL+ rate (23.65%) was the highest in >10-year old group. The distribution of leukemia genes in different age groups was statistically significant (P <0.05).@*CONCLUSION@#The most common fusion gene of children with ALL in Yunnan is ETV6-RUNX1, followed by E2A-PBX1 and BCR-ABL.

Preliminary study on thyroid ultrasound image restoration algorithm based on deep learning / 中华超声影像学杂志

Objective:To explore the feasibility of deep learning-based restoration of obscured thyroid ultrasound images.Methods:A total of 358 images of thyroid nodules were retropectively collected from January 2020 to October 2021 at Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, and the images were randomly masked and restored using DeepFillv2. The difference in grey values between the images before and after restoration was compared, and 6 sonographers (2 chief physicians, 2 attending physicians, 2 residents) were invited to compare the rate of correctness of judgement and detection of image discrepancies. The ultrasound features of thyroid nodules (solid composition, microcalcifications, markedly hypoechoic, ill-defined or irregular margins, or extrathyroidal extensions, vertical orientation and comet-tail artifact) were extracted according to the Chinese Thyroid Imaging Reporting and Data System (C-TIRADS). The consistency of ultrasound features of thyroid nodules before and after restoration were compared.Results:The mean squared error of the images before and after restoration ranged from 0.274 to 0.522, and there were significant differences in the rate of correctness of judgement and detection of image discrepancies between physicians of different groups(all P<0.001). The overall accuracy rate was 51.95%, the overall detection rate was 1.79%, there were significant differences also within the chief physicians and resident groups (all P<0.001). The agreement rate of all ultrasound features of the nodules before and after image restoration was higher than 70%, over 90% agreement rate for features such as solid composition and comet-tail artifact. Conclusions:The algorithm can effectively repair obscured thyroid ultrasound images while preserving image features, which is expected to expand the deep learning image database, and promote the development of deep learning in the field of ultrasound images.

Decompressive craniotomy for malignant cerebral venous sinus thrombosis / 国际脑血管病杂志

Cerebral venous sinus thrombosis (CVST) is a rare type of cerebrovascular disease, accounting for about 0.5% of all strokes. About 4% of patients with CVST have supratentorial brain parenchymal lesions and brain edema sufficient to cause brain hernia and neurological deterioration, which is called malignant CVST. Malignant CVST refers to the clinical (loss of consciousness, unilateral or bilateral pupil dilation) and imaging signs of supratentorial cortical lesions (ischemia or hemorrhage) accompanied by tentorial hiatal hernia formation at the onset or after treatment with heparin. For patients with malignant CVST, decompressive craniectomy is not only a life-saving treatment, but also can make most patients achieve good functional outcome.

Discussion on the Underlying Disease of Wei （卫）-Qi-Ying （营）-Blood Syndrome Differentiation System： Taking Epidemic Cerebrospinal Meningitis as an Example / 中医杂志

Epidemic cerebrospinal meningitis shows a high degree of consistency with the law of transmission among wei （卫）-qi-ying （营）-blood， in terms of the onset of the season， contagiousness， symptoms， pathogenesis， as well as characteristics of the transmission. It is proposed to use epidemic cerebrospinal meningitis as an example to explore the underlying disease of wei-qi-ying-blood syndrome differentiation system. Epidemic meningitis invades the brain from the upper respiratory tract along the nervous system， and its overall pathogenesis follows from entering the lung system （prodromal period） to entering the blood （bacteremia period， sepsis period） and then entering the brain （shock period）. According to the four-dimensional qualitative principle of epidemic pathogen tropism， it corresponds to disease of both wei and qi syndrome， then blazing of both qi and ying syndrome， and then heat blocking pericardium， exuberant heat stirring wind， and internal block and external collapse syndrome. This article explored the laws of transmission among wei-qi-ying-blood and its underlying diseases described in On Warm Heat （《温热论》）， and revealed the original appearance of the disease model under the laws of transmission among wei-qi-ying-blood to guide the clinical practice.

Contribution of Traditional Chinese Medicine Combined with Conventional Medicine Treatment for a Long-Term Survivor of Heart Transplant with Severe COVID-19： A Case Report / 中医杂志

We report a case of a long-term survivor of heart transplant who developed severe COVID-19 and was treated with a traditional Chinese medicine combined with conventional medicine. Throughout the treatment， the patient received active conventional medical treatment， and traditional Chinese medicine interventions included tonifying qi， invigorating the spleen and transforming phlegm， promoting yang and eliminating stagnation， resolving dampness and dissipating phlegm， and promoting blood circulation and eliminating stasis. The main therapeutic principles adopted were to recuperating depleted yang and rescuing the patient from collapse and to resolve phlegm and promote water. Pogezilong Xuanbai Chengqi Decoction （破格子龙宣白承气汤） with modifications was administered. In summary， it is crucial to the timely adjust the immunosuppressive regimen， combine use of various anti-infective agents with a focus on COVID-19， to protect of cardiac and renal function， and to integrate traditional Chinese medicine in the entire treatment process. As this case is rare， the diagnostic and therapeutic methods in traditional Chinese medicine， the use of immunosuppressive agents， and follow-up monitoring strategies can be a valuable reference.

Exploration of Modern Integrated Chinese and Western Medicine Model：from Target to State / 中医杂志

It is the current confusion encountered by integrated Chinese and Western medicine that how to find the breakthrough direction of integrating Chinese and Western medicine， from crossover to integration to innovation， and open up a new horizon of integrated Chinese and Western medicine. The progress of Chinese medicine lay in expanding the scope of diagnosis and treatment with the help of modern diagnostic and therapeutic equipments and developing “micro” identification， while the progress of Western medicine lay in looking at “macro” and developing systemic medicine and integrated medicine， both of which are in the direction of each other. The “state-target identification and treatment” may become an important way to build a modern diagnosis and treatment system of integrated Chinese and Western medicine， and the thinking mode of “from target to state” is a further refinement and development on the basis of the theoretical system of “state-target identification and treatment”， which provided a clearer solution for the current stage of the integrated Chinese and Western medicine model， and pointed out the important development direction for the future integrated Chinese and Western medicine. From the perspective of strategic level and diagnosis and treatment practice， it integrated the “target-state” thinking mode into the modern diagnosis and treatment model of the integrated Chinese and Western medicine， i.e.， “Western medicine as the basis and treating with Chinese medicine； Chinese medicine as the basis and treating with Western medicine”. On the one hand， Western medicine should strengthen the reference to the traditional theories and holism of Chinese medicine， and advocate a higher level of education on the integrated Chinese and Western medicine under the guidance of the traditional theories of Chinese medicine. On the other hand， the “from target to state” mode of thinking should be applied to guide the establishment of diagnostic and treatment strategies and clinical selection of medicines in clinical practice， so as to locate the target and adjust the body state in a gradual and orderly manner， and to provide practical methods for the modern clinical work of the integrated Chinese and Western medicines. Chinese and Western medicine systems can learn from each other， combine organically， give full play to their respective strengths， and form an internal law， so as to make breakthroughs and innovations in the integrated Chinese and Western medicine model.

Research progress of tradition Chinese medicine treatment mechanism of systemic lupus erythematosus based on biomarkers / 药学实践杂志

Systemic lupus erythematosus (SLE) is an autoimmune disease with multiple organ involvement. There are still many limitations and individual differences in the treatment based on glucocorticoids and immunosuppressants. In recent years, more and more studies have shown that the combination of traditional Chinese medicine in the treatment of SLE has the advantages of good efficacy, low adverse reactions, and high safety. However, the exact regulatory mechanism and combined traditional Chinese medicine in the treatment of SLE are still unclear. This paper reviews the research on the mechanism of traditional Chinese medicine in the treatment of SLE from metabonomic, immune cells, lymphocyte factors and apoptosis, etc, provides ideas for exploring the mechanism of traditional Chinese medicine in the treatment of SLE with modern methods.

Acupuncture-Neuroimaging Research Trends over Past Two Decades: A Bibliometric Analysis / 中国结合医学杂志

OBJECTIVE@#To identify topics attracting growing research attention as well as frontier trends of acupuncture-neuroimaging research over the past two decades.@*METHODS@#This paper reviewed data in the published literature on acupuncture neuroimaging from 2000 to 2020, which was retrieved from the Web of Science database. CiteSpace was used to analyze the publication years, countries, institutions, authors, keywords, co-citation of authors, journals, and references.@*RESULTS@#A total of 981 publications were included in the final review. The number of publications has increased in the recent 20 years accompanied by some fluctuations. Notably, the most productive country was China, while Harvard University ranked first among institutions in this field. The most productive author was Tian J with the highest number of articles (50), whereas the most co-cited author was Hui KKS (325). Evidence-Based Complementary and Alternative Medicine (92) was the most prolific journal, while Neuroimage was the most co-cited journal (538). An article written by Hui KKS (2005) exhibited the highest co-citation number (112). The keywords "acupuncture" (475) and "electroacupuncture" (0.10) had the highest frequency and centrality, respectively. Functional magnetic resonance imaging (fMRI) ranked first with the highest citation burst (6.76).@*CONCLUSION@#The most active research topics in the field of acupuncture-neuroimaging over the past two decades included research type, acupoint specificity, neuroimaging methods, brain regions, acupuncture modality, acupoint specificity, diseases and symptoms treated, and research type. Whilst research frontier topics were "nerve regeneration", "functional connectivity", "neural regeneration", "brain network", "fMRI" and "manual acupuncture".

Investigation of extrauterine growth restriction in very preterm infants in Chinese neonatal intensive care units / 中华儿科杂志

Objective: To comprehensively assess the current status of extrauterine growth restriction (EUGR) in very preterm infants (VPI) and its associated factors in Chinese neonatal intensive care units (NICU). Methods: In this cohort study, 6 179 preterm infants born at <32 weeks' gestation were included, who were admitted to 57 hospitals in the China Neonatal Network in 2019 and hospitalized for ≥7 days. EUGR was evaluated by a cross-sectional definition (weight at discharge<10th percentile for postmenstrual age), a longitudinal definition (decline in weight Z score>1 from birth to discharge), and weight growth velocity. The comparison between infants with and without EUGR was conducted by t-test, Mann-Whitney U test or χ2 test as appropriate. Multivariable Logistic regression models were used to evaluate associations between EUGR with different definitions and maternal and neonatal factors, clinical practices, and neonatal morbidities. Results: A total of 6 179 VPI were enrolled in the study, with a gestational age of (29.8±1.5) weeks and birth weight of (1 365±304) g; 56.2% (3 474) of them were male. Among them, 48.4% (2 992 VPI) were cross-sectional EUGR and 74.9% (4 628 VPI) were longitudinal EUGR. Z score of weight was (0.13±0.78) at birth and decrease to (-1.35±0.99) at discharge. The weight growth velocity was 10.13 (8.42, 11.66) g/(kg·d). Multivariate Logistic regression analysis showed that among the influential factors that could be intervened after birth, late attainment of full enteral feeds (ORadjust=1.01, 95%CI 1.01-1.02, P<0.001; ORadjust=1.01, 95%CI 1.01-1.02, P<0.001), necrotizing enterocolitis≥Ⅱstage (ORadjust=2.64, 95%CI 1.60-4.35, P<0.001; ORadjust=1.62, 95%CI 1.10-2.40, P<0.001) and patent ductus arteriosus (ORadjust=1.94, 95%CI 1.50-2.51, P<0.001; ORadjust=1.63, 95%CI 1.29-2.06, P<0.001) were all associated with increased risks of both cross-sectional and longitudinal EUGR. In addition, late initiation of enteral feeds (ORadjust=1.06, 95%CI 1.02-1.09, P=0.020) and respiratory distress syndrome (ORadjust=1.45, 95%CI 1.24-1.69, P<0.001) were all associated with cross-sectional EUGR. Breast milk feeding (ORadjust=1.33, 95%CI 1.05-1.68, P<0.001) was associated with a higher risk of longitudinal EUGR. Conclusions: The incidence of EUGR in VPI in China is high. Some modifiable risk factors provide priorities to improve postnatal growth for VPI. Nutritional management of VPI and the efforts to decrease the incidence of complications are still the focus of clinical management in China.

Practice and principle of traditional Chinese medicine for the prevention and treatment of COVID-19 / 医学前沿

Traditional Chinese medicine (TCM) has played an important role in the prevention and treatment of Coronavirus disease 2019 (COVID-19) epidemic in China. The integration of Chinese and Western medicine is an important feature of Chinese COVID-19 prevention and treatment. According to a series of evidence-based studies, TCM can reduce the infection rate of severe acute respiratory syndrome coronavirus 2 in high-risk groups. For patients with mild and moderate forms of COVID-19, TCM can relieve the related signs and symptoms, shorten the period of nucleic-acid negative conversion, and reduce conversion rate to the severe form of the disease. For COVID-19 patients with severe and critical illnesses, TCM can improve inflammatory indicators and blood oxygen saturation, shorten the hospital stay, and reduce the mortality rate. During recovery, TCM can improve patients' symptoms, promote organ function recovery, boost the quality of patients' life, and reduce the nucleic-acid repositive conversion rate. A series of mechanism research studies revealed that capability of TCM to treat COVID-19 through antiviral and anti-inflammatory effects, immune regulation, and protection of organ function via a multicomponent, multitarget, and multipathway approach.

Human 8-cell embryos enable efficient induction of disease-preventive mutations without off-target effect by cytosine base editor

Approximately 140 million people worldwide are homozygous carriers of APOE4 (ε4), a strong genetic risk factor for late onset familial and sporadic Alzheimer's disease (AD), 91% of whom will develop AD at earlier age than heterozygous carriers and noncarriers. Susceptibility to AD could be reduced by targeted editing of APOE4, but a technical basis for controlling the off-target effects of base editors is necessary to develop low-risk personalized gene therapies. Here, we first screened eight cytosine base editor variants at four injection stages (from 1- to 8-cell stage), and found that FNLS-YE1 variant in 8-cell embryos achieved the comparable base conversion rate (up to 100%) with the lowest bystander effects. In particular, 80% of AD-susceptible ε4 allele copies were converted to the AD-neutral ε3 allele in human ε4-carrying embryos. Stringent control measures combined with targeted deep sequencing, whole genome sequencing, and RNA sequencing showed no DNA or RNA off-target events in FNLS-YE1-treated human embryos or their derived stem cells. Furthermore, base editing with FNLS-YE1 showed no effects on embryo development to the blastocyst stage. Finally, we also demonstrated FNLS-YE1 could introduce known protective variants in human embryos to potentially reduce human susceptivity to systemic lupus erythematosus and familial hypercholesterolemia. Our study therefore suggests that base editing with FNLS-YE1 can efficiently and safely introduce known preventive variants in 8-cell human embryos, a potential approach for reducing human susceptibility to AD or other genetic diseases.

A case of podocyte infolding glomerulopathy / 中华肾脏病杂志

Podocyte infolding glomerulopathy (PIG) is a pathologic type of podocyte glomerulopathy reported recently. The characteristic is that the ultrastructure related to podocytes, such as microspheres and microtubules, are folded into the glomerular basement membrane (GBM) under electron microscope. At present, there are few reports about this disease at home and abroad, and most of them are concentrated in Japan. The clinical characteristics and pathogenesis of PIG are still unclear. In this paper, we report a case of clinical manifestations of nephrotic syndrome, renal biopsy indicated PIG, after the treatment of glucocorticoid, hydroxychloroquine and tacrolimus, the patient's clinical symptoms were relieved and urinary protein decreased.

Clinical features of 6 children with uridine-responsive developmental epileptic encephalopathy 50 caused by CAD gene variants / 中华儿科杂志

Objective: To analyze the clinical features of children with uridine responsive developmental epileptic encephalopathy 50 (DEE50) caused by CAD gene variants. Methods: A retrospective study was conducted on 6 patients diagnosed with uridine-responsive DEE50 caused by CAD gene variants at Beijing Children's Hospital and Peking University First Hospital from 2018 to 2022. The epileptic seizures, anemia, peripheral blood smear, cranial magnetic resonance imaging (MRI), visual evoked potential (VEP), genotype features and the therapeutic effect of uridine were descriptively analyzed. Results: A total of 6 patients, including 3 boys and 3 girls, aged 3.5(3.2,5.8) years, were enrolled in this study. All patients presented with refractory epilepsy, anemia with anisopoikilocytosis and global developmental delay with regression. The age of epilepsy onset was 8.5 (7.5, 11.0) months, and focal seizures were the most common seizure type (6 cases). Anemia ranged from mild to severe. Four patients had peripheral blood smears prior to uridine administration, showing erythrocytes of variable size and abnormal morphology, and normalized at 6 (2, 8) months after uridine supplementation. Two patients suffered from strabismus, 3 patients had VEP examinations, indicating of suspicious optic nerve involvement, and normal fundus examinations. VEP was re-examined at 1 and 3 months after uridine supplementation, suggesting significant improvement or normalization. Cranial MRI were performed at 5 patients, demonstrating cerebral and cerebellar atrophy. They had cranial MRI re-examined after uridine treatment with a duration of 1.1 (1.0, 1.8) years, indicating significant improvement in brain atrophy. All patients received uridine orally at a dose of 100 mg/(kg·d), the age at initiation of uridine treatment was 1.0 (0.8, 2.5) years, and the duration of treatment was 2.4 (2.2, 3.0) years. Immediate cession of seizures was observed within days to a week after uridine supplementation. Four patients received uridine monotherapy and were seizure free for 7 months, 2.4 years, 2.4 years and 3.0 years respectively. One patient achieved seizure free for 3.0 years after uridine supplementation and had discontinued uridine for 1.5 years. Two patients were supplemented with uridine combined with 1 to 2 anti-seizure medications and had a reduced seizure frequency of 1 to 3 times per year, and they had achieved seizure free for 8 months and 1.4 years respectively. Conclusions: The clinical manifestations of DEE50 caused by CAD gene variants present a triad of refractory epilepsy, anemia with anisopoikilocytosis, and psychomotor retardation with regression, accompanied by suspected optic nerve involvement, all of which respond to uridine treatment. Prompt diagnosis and immediate uridine supplementation could lead to significant clinical improvement.

Study of ErChen decoction on the treatment of obesity polycystic ovary syndrome and obesity infertility / 药学实践杂志

Objective To explore the potential mechanism of Erchen decoction in the treatment of obese polycystic ovary syndrome and obese infertility, in order to provide theoretical basis for “treating different diseases with same method”. Methods The active ingredients and targets of Erchen decoction were obtained from TCMSP database, and the targets of obese polycystic ovary syndromes and obese infertility were obtained from GeneCard database. Active ingredient-target network was constructed by Cytoscape 3.7.1, and protein-protein interaction network and core target were obtained from STRING. GO and KEGG enrichment analysis were performed by Cytoscape 3.7.1 and online software. Results 125 ingredients and 218 targets of Erchen decoction were obtained. There were 2 783 target genes for obese infertility and 2 962 target genes for obese polycystic ovary syndrome. Erchen decoction has a total of 117 target genes in the treatment of obese infertility and obese polycystic ovary syndromes, which proves the principle of “treating different diseases with same method”. Potential active ingredients include quercetin, kaempferol, naringin, baicalin and formononetin. PPI showed that STAT3, JUN, AKT1, MAPK3, MAPK1, MAPK14, IL-6 and FOS were the core targets of “treating different diseases with same method”. Molecular docking results showed that quercetin, kaempferol, etc. had good binding ability with JUN. GO and KEGG enrichment analysis showed that AGE-RAGE signaling pathway, IL-17 signaling pathway and endocrine resistance might be the key pathways for the “treating different diseases with same method” of Erchen decoction. Conclusion Erchen decoction treating "different diseases with same method" involves same targets and same pathways, which can provide reference for future experimental research.

Influence of Tuina plus oxiracetam on serum inflammatory factors and oxidative stress in mild vascular dementia patients / 针灸推拿医学（英文版）

Objective: To observe the clinical efficacy of Tuina (Chinese therapeutic massage) plus oxiracetam in treating mild vascular dementia (VD) and seek its underlying mechanism. Methods: Ninety-six patients with mild VD were randomized into an observation group and a control group, with 47 cases in the observation group and 49 cases in the control group. The control group received oral oxiracetam capsules for treatment, and the observation group was given additional Tuina treatment. Before and after treatment, the mini-mental state examination (MMSE) was adopted to assess the patient's cognitive function; the activities of daily living (ADL) scale was used to evaluate their ability to conduct daily activities; changes in the serum inflammatory factors and oxidative stress indicators were also detected. Results: After treatment, the serum content of malondialdehyde (MDA) decreased in both groups (P<0.05) and was lower in the observation group than in the control group (P<0.05); the serum contents of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) increased in both groups (P<0.05) and were higher in the observation group than in the control group (P<0.05); the serum contents of interleukin (IL)-1, tumor necrosis factor (TNF)-α, IL-6, and IL-8 declined in both groups (P<0.05) and were lower in the observation group than in the control group (P<0.05). After the intervention, the levels of systolic velocity (Vs) and mean velocity (Vm) of the middle cerebral artery elevated, and the pulsatility index (PI) dropped in patients in the two groups, showing significant intra-group differences (P<0.05); the levels of Vs and Vm in the observation group were higher than those in the control group, and the PI was lower in the observation group than in the control group, showing significant between-group differences (P<0.05). The MMSE and ADL scores increased in both groups after the intervention (P<0.05) and were higher in the observation group than in the control group (P<0.05). Conclusion: In the treatment of mild VD, Tuina plus oxiracetam can improve the cerebral blood supply, ADL, and cognitive function; the mechanism may be associated with the reduction of oxidative stress damages and inflammatory reactions.

Mechanisms of catapol inhibiting differentiation and glycolysis of Thl7 cells through MiR-143-3p / 中国药理学通报

Aim To investigate the mechanism of eata- pol (CAT) inhibiting differentiation and glyeolysis of Thl7 eel Is through miR-143-3p.Method The peripheral hloorl CD4 ∗ T eells of HA patients were obtained to deteet the expression of miR-143-3p and the mRNA levels of key glycolytic enzymes, ineluding glucose transporter 1 ( Glutl ) , hexokinase 2 ( HK2 ) , pyruvate kinase 2 (PKM2) , laetate dehydrogenase A ( LDHA).The differentiation of Thl7 eells was induced in vitro, and the ShRNA/lentivirus was applied to achieve the overexpression or knockdown of miR- 143-3 p.Un-transfected eells were divided into control group and CAT group (20, 40, 80 mg • L 1 ) , and transfected eells were divided into four groups: negative control group, miR-143-3p inhibitor group, miR- 143-3p mimies group, miR-143-3p inhibitor + CAT group.The percentage of Thl7 eells was deteeted by flow cytometry, and the level of IL-17A was detected by EL1SA.Quantitative real-time PCR was used to detect the mRNA expression of miR-143-3p and key glycolytic enzymes, and the levels of pyruvate and lactate were also detected.Results The mRNA expression of miR-143-3p in RA peripheral blood CD4 ∗ T cells was negatively correlated with disease severity ( DAS28 ) , transcription factor ROR-yt, and the key glycolytic enzymes Glutl/HK2/LDHA.Compared with negative control group, the down-expression of miR-143-3p markedly elevated the mRNA expression of ROR-yt, Glutl, HK2, LDHA, and the levels of IL-17A, pyruvate, lactate.Catalpol groups significantly up-regula- ted the expression of miR-143-3p, decreased the mRNA expression of HK2/LDHA and the levels of pvru- vate/lactate, and inhibited Thl7 cells differentiation.Compared with miR - 1 4 3 - 3 p inhibitor group , catapol could significantly inhibit the abnormal up-regulated of HK2/LDHA mRNA relative expression, pyruvate/lactate levels and the abnormal differentiation of Thl7 eells.Conclusion MiR-143-3p inhibits the differentiation and glycolysis of Thl7 cells.Catalpol could sup-press the glycolysis and differentiation of Thl7 eells by regulating mill-143-3p.

Analysis of clinical significance and prognostic impact of TET2 single nucleotide polymorphism I1762V in patients with acute myeloid leukemia / 中华血液学杂志

Objective: This study aimed to investigate the clinical and prognostic significance of TET2 single nucleotide polymorphism I1762V in patients with acute myeloid leukemia (AML) . Methods: The high-throughput sequencing method was used to sequence 58 hematological tumor-related genes in bone marrow samples from 413 patients with AML. TET2 I1762V and other somatic mutations were annotated and compared with patients' clinical information and prognosis. Results: I1762V was found in 154 patients with AML, which was significantly different from the general population in NyuWa Chinese Population Variant Database (χ(2)=72.4, P<0.001) . I1762V was not related to sex, age, and karyotype of patients with AML (P>0.05) . Patients with I1762V had a significantly higher proportion of NPM1 and KIT gene mutations than others (P<0.001) . NPM1 and KIT mutations were mutually exclusive. The survival analysis results revealed that the overall survival (OS) and progression-free survival (PFS) of patients with AML with I1762V were significantly greater than those of wild-type patients (HR=0.57, P=0.030; HR=0.55, P=0.020) , whereas the OS and PFS in patients with AML with DNMT3A mutation (with or without I1762V mutation) were lower than those of wild-type patients (HR=1.79, P=0.030; HR=1.74, P=0.040) . Conclusion: TET2 SNP I1762V has been linked to AML. I1762V is a prognostic factor of patients with AML, which can be used to guide the treatment and evaluate the prognosis of AML.

Research progress on mitochondrial oxidative stress and corresponding targeted delivery systems in Alzheimer's disease / 药学学报

Mitochondrial oxidative stress has been recognized as a preliminary and critical factor that aggravates the pathological cascade of Alzheimer's disease, which induces the production of β-amyloid protein, upregulates the expression of phosphorylated tau protein and triggers oxidative damage to lipids, proteins and mitochondrial deoxyribonucleic acid. Central neurons are more vulnerable to oxidative stress than non-neuronal cells due to their high oxygen demand, abundant unsaturated fatty acids and antioxidant enzymes deficiency. On this account, this review introduces the causes of mitochondrial oxidative stress, and analyzes the important role of mitochondrial oxidative stress in the pathogenesis of Alzheimer's disease. Meanwhile, the review focuses on the design and intervention strategies of drug delivery systems targeting mitochondrial oxidative stress in neurons, aiming to provide new ideas for the prevention and treatment of Alzheimer's disease.

Identification of Key Genes and Pathways in Peripheral Blood Mononuclear Cells of Type 1 Diabetes Mellitus by Integrated Bioinformatics Analysis

Background@#The onset and progression of type 1 diabetes mellitus (T1DM) is closely related to autoimmunity. Effective monitoring of the immune system and developing targeted therapies are frontier fields in T1DM treatment. Currently, the most available tissue that reflects the immune system is peripheral blood mononuclear cells (PBMCs). Thus, the aim of this study was to identify key PBMC biomarkers of T1DM. @*Methods@#Common differentially expressed genes (DEGs) were screened from the Gene Expression Omnibus (GEO) datasets GSE9006, GSE72377, and GSE55098, and PBMC mRNA expression in T1DM patients was compared with that in healthy participants by GEO2R. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and protein-protein interaction (PPI) network analyses of DEGs were performed using the Cytoscape, DAVID, and STRING databases. The vital hub genes were validated by reverse transcription-polymerase chain reaction using clinical samples. The disease-gene-drug interaction network was built using the Comparative Toxicogenomics Database (CTD) and Drug Gene Interaction Database (DGIdb). @*Results@#We found that various biological functions or pathways related to the immune system and glucose metabolism changed in PBMCs from T1DM patients. In the PPI network, the DEGs of module 1 were significantly enriched in processes including inflammatory and immune responses and in pathways of proteoglycans in cancer. Moreover, we focused on four vital hub genes, namely, chitinase-3-like protein 1 (CHI3L1), C-X-C motif chemokine ligand 1 (CXCL1), matrix metallopeptidase 9 (MMP9), and granzyme B (GZMB), and confirmed them in clinical PBMC samples. Furthermore, the disease-gene-drug interaction network revealed the potential of key genes as reference markers in T1DM. @*Conclusion@#These results provide new insight into T1DM pathogenesis and novel biomarkers that could be widely representative reference indicators or potential therapeutic targets for clinical applications.