Hematopoietic stem cell division is governed by distinct RUNX1 binding partners.

A defined number of hematopoietic stem cell (HSC) clones are born during development and expand to form the pool of adult stem cells. An intricate balance between self-renewal and differentiation of these HSCs supports hematopoiesis for life. HSC fate is determined by complex transcription factor networks that drive cell-type specific gene programs. The transcription factor RUNX1 is required for definitive hematopoiesis, and mutations in Runx1 have been shown to reduce clonal diversity. The RUNX1 cofactor, CBFý, stabilizes RUNX1 binding to DNA, and disruption of their interaction alters downstream gene expression. Chemical screening for modulators of Runx1 and HSC expansion in zebrafish led us to identify a new mechanism for the RUNX1 inhibitor, Ro5-3335. We found that Ro5-3335 increased HSC divisions in zebrafish, and animals transplanted with Ro5-3335 treated cells had enhanced chimerism compared to untreated cells. Using human CD34+ cells, we show that Ro5-3335 remodels the RUNX1 transcription complex by binding to ELF1, independent of CBFý. This allows specific expression of cell cycle and hematopoietic genes that enhance HSC self-renewal and prevent differentiation. Furthermore, we provide the first evidence to show that it is possible to pharmacologically increase the number of stem cell clones in vivo , revealing a previously unknown mechanism for enhancing clonal diversity. Our studies have revealed a mechanism by which binding partners of RUNX1 determine cell fate, with ELF transcription factors guiding cell division. This information could lead to treatments that enhance clonal diversity for blood diseases.

Meroterpenoids from Marine Sponge Hyrtios sp. and Their Anticancer Activity against Human Colorectal Cancer Cells.

Two new meroterpenoids, hyrtamide A (1) and hyrfarnediol A (2), along with two known ones, 3-farnesyl-4-hydroxybenzoic acid methyl ester (3) and dictyoceratin C (4), were isolated from a South China Sea sponge Hyrtios sp. Their structures were elucidated by NMR and MS data. Compounds 2-4 exhibited weak cytotoxicity against human colorectal cancer cells (HCT-116), showing IC50 values of 41.6, 45.0, and 37.3 µM, respectively. Furthermore, compounds 3 and 4 significantly suppressed the invasion of HCT-116 cells while also downregulating the expression of vascular endothelial growth factor receptor 1 (VEGFR-1) and vimentin proteins, which are key markers associated with angiogenesis and epithelial-mesenchymal transition (EMT). Our findings suggest that compounds 3 and 4 may exert their anti-invasive effects on tumor cells by inhibiting the expression of VEGFR-1 and impeding the process of EMT.

Application value of combined coagulation function indicators in monitoring hypercoagulable state of patients with colorectal cancer after chemotherapy / 中国癌症杂志

Background and purpose:The plasma used for routine coagulation test(CCT)can only reflect a single component at a certain coagulation time point/segment,while thromboelastography(TEG)can depict the overall dynamic process curve of coagulation and fibrinolysis,which can more independently and completely reflect the true state of the blood and can serve as a supplement to coagulation function testing.This study aimed to evaluate the application value of combined coagulation function indexes in monitoring the hypercoagulable state of patients with colorectal cancer after chemotherapy,and to explore the risk factors of thrombosis in patients with colorectal cancer after chemotherapy,so as to provide reference for clinical monitoring of hypercoagulable state.Methods:A total of 160 patients with colorectal cancer from Fudan University Shanghai Cancer Center from June 2021 to June 2023 were selected as the experimental group,and 80 healthy subjects were selected as the control group.Then the experimental group was divided into a group without thrombosis(82 cases)and a group with thrombosis(78 cases)according to whether they had thrombosis or not.The determinations of thromboelastography(TEG)[coagulation reaction time(R),coagulation formation time(K),blood clot formation rate(α-Angle),maximum amplitude(MA)and coagulation index(CI)],conventional coagulation tests(CCT)[activated partial thromboplastin time(APTT),prothrombin time(PT),thrombin time(TT),fibrinogen(Fib),D-dimer(DD),fibrinogen degradation products(FDP)]and platelet count(PLT)were studied among three groups.With or without thrombosis as the criterion of hypercoagulable state,statistically significant indicators were selected to be included in the binary logistic regression analysis,and the receiver operating characteristic(ROC)curve was drawn to analyze the diagnostic efficacy of single and combined detection of the coagulation function indicators for hypercoagulable state in patients with colorectal cancer after chemotherapy.Basic information,tumor stage and Autar score of deep vein thrombosis were collected in 160 patients with colorectal cancer.Logistic regression analysis was performed to explore the risk factors of thrombosis.This study was approved by the Ethics Committee of Fudan University Shanghai Cancer Center(number:050432-4-2108*).Results:Compared with the control group,the R,TT and PLT of the group with thrombosis were decreased(P＜0.05),while APTT,PT,DD and FDP were increased(P＜0.05).The differences in various indicators between the group with thrombosis and the control group were statistically significant(P＜0.05).Compared with the group without thrombosis,the K in the group with thrombosis decreased(P＜0.05),while Angle,MA,CI,FIB,DD and FDP all increased(P＜0.05).ROC curve analysis showed that in the assessment of hypercoagulable state in patients with colorectal cancer after chemotherapy,the area under curve(AUC)of TEG was 0.756,sensitivity was 67.5%,and specificity was 73.8%.The AUC of CCT was 0.691,sensitivity was 78.8%,and specificity was 56.2%.The combined detection AUC was 0.840,sensitivity was 80.0%,and specificity was 77.5%.In the analysis of risk factors,tumor stage,distant metastasis and Autar score were correlated with thrombus formation in patients with colorectal cancer after chemotherapy(P＜0.05),and the differences of the three risk factors in K,Angle,MA,CI,Fib,DD and FDP were statistically significant(P＜0.05).Conclusion:K,Angle,MA,CI,Fib,DD and FDP are the main indicators to reflect the hypercoagulable state,and the combined detection of TEG and CCT can better reflect the coagulation state of patients with colorectal cancer after chemotherapy.Tumor stage Ⅲ to Ⅳ,distant metastasis and high Autar score are risk factors for thrombosis.The incidence of thrombosis can be reduced by monitoring the relevant coagulation indicators in the high-risk population.

Relationship between lifestyle and the comorbidity of myopia and depressive symptoms among primary and secondary school students in Nanjing / 中国学校卫生

Objective@#To explore the relationship between lifestyle and myopia and depressive symptoms comorbidity among primary and secondary school students in Nanjing, so as to provide a scientific basis for developing effective prevention measures.@*Methods@#In October 2022, a stratified cluster random sampling method was used to select primary and secondary school students aged 9-19 years in 4 urban and 4 suburban districts in Nanjing as the research subjects. A total of 10 498 students were included for physical examination and questionnaire survey by using the student health condition and influencing factors questionnaire. Chisquare test was used for univariate analysis, and multifactor Logistic regression analysis was used to analyze the relationship between students lifestyle and the cooccurrence of myopia and depressive symptoms.@*Results@#The prevalence of comorbidity of screening positive myopia and depression among primary and secondary school students in Nanjing was 18.11%. The prevalence of comorbidity was higher in girls (20.97%) than in boys (15.47%), higher in boarding students (31.31%) than in nonboarding students (16.51%), and higher in high school students than in middle and primary school students (28.63%, 19.10%, 7.76%), with statistically significant differences (χ2=53.49, 149.31, 522.55, P<0.01). Multivariate Logistic regression results showed that smoking (OR=1.51), drinking (OR=2.36), looking at electronic screens in dim conditions (OR=2.40), screen time ≥2 h/d(OR=1.50), afterschool homework time ≥2 h/d(OR=1.48) were positively correlated with the prevalence of comorbidity of screening positive myopia and depressive symptoms, healthy diet (OR=0.67), outdoor activities during breaks (OR=0.80), sufficient sleep (OR=0.64), meeting physical activity standards (OR=0.74) and outdoor activity time ≥2 h/d(OR=0.84) were negatively correlated with the prevalence of comorbidity of screening positive of myopia and depressive symptoms (P<0.05).@*Conclusions@#The lifestyle of primary and secondary school students in Nanjing is related to the comorbidity of myopia and depressive symptoms. Schools and families should carry out relevant education and intervention measures to promote students to develop good living habits and jointly prevent the occurrence of myopia and depressive symptoms.

Co(III)-Catalyzed C6-Selective C-H Activation/Pyridine Migration of 2-Pyridones with Propiolates.

A versatile Co(III)-catalyzed C6-selective C-H activation/pyridine migration of 2-pyridones with available propiolates as coupling partners was demonstrated. This method features high atom economy, excellent regioselectivity, and good functional group tolerance by employing an inexpensive Co(III) catalyst under mild reaction conditions. Moreover, gram-scale synthesis and late-stage modifications of pharmaceuticals were performed to prove the effectiveness of these synthetic approaches.

Transcutaneous Electrical Acupoint Stimulation Promotes PGC-1α Mediated Mitochondrial Biogenesis and Antioxidant Stress to Protect Cognitive Function in Vascular Dementia Rats / 生物化学与生物物理进展

ObjectiveThe purpose of this study was to investigate the effects of transcutaneous electrical acupoint stimulation (TEAS) on cognitive function of vascular dementia (VD) rats and its mechanism. MethodsVD rat model was established by modified two-vessel occlusion (2-VO). After modeling, TEAS and electroacupuncture (EA) were used to stimulate Baihui and Zusanli points of rats respectively for 14 d. After treatment, novel object recognition test, Morris water maze test, and Y maze test were used to evaluate the spatial memory and learning ability of rats. Hematoxylin and eosin staining was used to observe the morphology of hippocampal neurons. Transmission electron microscopy was used to observe the ultrastructure of hippocampal mitochondria. Enzyme-linked immunosorbent assay kits were used to detected the levels of SOD, CAT, GSH-Px, MDA and ROS in serum of rats. Western blot was used to detect the expression of PGC-1α, TFAM, HO-1, NQO1 proteins in the hippocampus, Keap1 protein in the cytoplasm and Nrf2, NRF1 proteins in the nucleus. ResultsAfter treatment for 14 d, compared to the model group, the escape latency of VD rats decreased, while the discrimination index, the times of rats crossing the original platform area, the residence time in the original platform quadrant, and the percentage of alternation increased. TEAS can improve the structure of hippocampal neurons and mitochondria of VD rats, showing that neurons were arranged more regularly and distributed more evenly, nuclear membrane and nucleoli were clearer, and mitochondrial swelling were reduced, mitochondrial matrix density were increased, and mitochondrial cristae were more obvious. The levels of SOD, GSH-Px and CAT in serum increased significantly, while the concentration of MDA and ROS decreased. TEAS also up-regulated the expression levels of PGC-1α TFAM, NQO1 and HO-1 proteins in the hippocampus and Nrf2, NRF1 proteins in the nucleus, but down-regulated the Keap1 protein in the cytoplasm. ConclusionTEAS can improve cognition, hippocampal neurons and mitochondrial structure of VD rats, and the effect is better than EA. The mechanism may be the activation of PGC-1α mediated mitochondrial biogenesis and antioxidant stress, which also provides a potential therapeutic technology and experimental basis for the treatment of VD.

Chinese expert consensus recommendations for the administration of immune checkpoint inhibitors to special cancer patient populations.

Immune checkpoint inhibitors (ICIs) targeting programmed cell death 1, programmed cell death ligand 1, and cytotoxic T lymphocyte-associated antigen-4 have shown significantly durable clinical benefits and tolerable toxicities and have improved the survival of patients with various types of cancer. Since 2018, the National Medical Products Administration of China has approved 17 ICIs as the standard treatment for certain advanced or metastatic solid tumors. As ICIs represent a broad-spectrum antitumor strategy, the populations eligible for cancer immunotherapy are rapidly expanding. However, the clinical applications of ICIs in cancer patient populations with special issues, a term that refers to complex subgroups of patients with comorbidities, special clinical conditions, or concomitant medications who are routinely excluded from prospective clinical trials of ICIs or are underrepresented in these trials, represent a great real-world challenge. Although the Chinese Society of Clinical Oncology (CSCO) has provided recommendations for screening before the use of ICIs in special populations, the recommendations for full-course management remain insufficient. The CSCO Expert Committee on Immunotherapy organized leading medical oncology and multidisciplinary experts to develop a consensus that will serve as an important reference for clinicians to guide the proper application of ICIs in special patient populations. This article is a translation of a study first published in Chinese in The Chinese Clinical Oncology (ISSN 1009-0460, CN 32-1577/R) in May 2022 (27(5):442-454). The publisher of the original paper has provided written confirmation of permission to publish this translation in Therapeutic Advances in Medical Oncology.

Evaluation of bladder filling effects on the dose distribution during radiotherapy for cervical cancer based on daily CT images.

PURPOSE: This study aimed to assess the effects of bladder filling during cervical cancer radiotherapy on target volume and organs at risk (OARs) dose based on daily computed tomography (daily-CT) images and provide bladder-volume-based dose prediction models. METHODS: Nineteen patients (475 daily-CTs) comprised the study group, and five patients comprised the validation set (25 daily-CTs). Target volumes and OARs were delineated on daily-CT images and the treatment plan was recalculated accordingly. The deviation from the planning bladder volume (DVB), the correlation between DVB and clinical (CTV)/planning (PTV) target volume in terms of prescribed dose coverage, and the relationship of small bowel volume and bladder dose with the ratio of bladder volume (RVB) were analyzed. RESULTS: In all cases, the prescribed dose coverage in the CTV was >95% when DVB was <200 cm3 , whereas that in the PTV was >95% when RVB was <160%. The ratio of bladder V45 Gy to the planning bladder V45 Gy (RBV45 ) exhibited a negative linear relationship with RVB (RBV45  = -0.18*RVB + 120.8; R2  = 0.80). Moreover, the ratio of small bowel volume to planning small bowel volume (RVS) exhibited a negative linear relationship with RVB (RVS = -1.06*RVB +217.59; R2  = 0.41). The validation set results showed that the linear model predicted well the effects of bladder volume changes on target volume coverage and bladder dose. CONCLUSIONS: This study assessed dosimetry and volume effects of bladder filling on target and OARs based on daily-CT images. We established a quantitative relationship between these parameters, providing dose prediction models for cervical cancer radiotherapy.

Spectral analysis of multiple scattering factors of turbid media for glucose measurement using near-infrared spectroscopy.

Significance: Near-infrared (NIR) diffuse reflectance spectroscopy has been widely used for non-invasive glucose measurement in humans, as glucose can induce a significant and detectable optical signal change in tissue. However, the scattering-dominated glucose spectrum in the range of 1000 to 1700 nm is easily confused with many other scattering factors, such as particle density, particle size, and tissue refractive index. Aim: Our aim is to identify the subtle distinctions between glucose and these factors through theoretical analysis and experimental verification, in order to employ suitable methods for eliminating these interferences, thus increasing the accuracy of non-invasive glucose measurement. Approach: We present a theoretical analysis of the spectra of 1000 to 1700 nm for glucose and some scattering factors, which is then verified by an experiment on a 3% Intralipid solution. Results: We found that both the theoretical and experimental results show that the effective attenuation coefficient of glucose has distinct spectral characteristics, which are distinct from the spectra caused by particle density and refractive index, particularly in the range of 1400 to 1700 nm. Conclusions: Our findings can offer a theoretical foundation for eliminating these interferences in non-invasive glucose measurement, aiding mathematical methods to model appropriately and enhance the accuracy of glucose prediction.

Palladium(II)-Catalyzed Remote meta-C-H Functionalization of Arenes Enabled by Multitasking Oxyamides as the Linker.

A palladium-catalyzed olefination of meta-C-H bonds in arenes containing oxyamides using a nitrile template as the directing group has been established. The methodology exhibited high meta-selectivity and tolerated different functional groups such as benzyloxyamides and olefin substrates. The desired products were obtained in good yields. This approach enabled the modification of natural products and drugs and was also applicable on the gram-scale. Furthermore, the directing template was readily removed by selective cleavage of the amide bond or the O-N bond to obtain meta-functionalized hydroxylamines and benzyl alcohols. The proposed method holds great potential for the design of novel drugs.

Integration of Handheld Ultrasound or Automated Breast Ultrasound among Women with Negative Mammographic Screening Findings: A Multi-center Population-based Study in China.

RATIONALE AND OBJECTIVES: This study assessed the role of second-look automated breast ultrasound (ABUS) adjunct to mammography (MAM) versus MAM alone in asymptomatic women and compared it with supplementing handheld ultrasound (HHUS). MATERIALS AND METHODS: Women aged 45 to 64 underwent HHUS, ABUS, and MAM among six hospitals in China from 2018 to 2022. We compared the screening performance of three strategies (MAM alone, MAM plus HHUS, and MAM plus ABUS) stratified by age groups and breast density. McNemar's test was used to assess differences in the cancer detection rate (CDR), the false-positive biopsy rate, sensitivity, and specificity of different strategies. RESULTS: Of 19,171 women analyzed (mean [SD] age, 51.54 [4.61] years), 72 cases of breast cancer (3.76 per 1000) were detected. The detection rates for both HHUS and ABUS combined with MAM were statistically higher than those for MAM alone (all p < 0.001). There was no significant difference in cancer yields between the two integration strategies. The increase in CRD of the integrated strategies was higher in women aged 45-54 years with denser breasts compared with MAM alone (all p < 0.0167). In addition, the false-positive biopsy rate of MAM plus ABUS was lower than that of MAM plus HHUS (p = 0.025). Moreover, the retraction in ABUS was more frequent in cases detected among MAM-negative results. CONCLUSION: Integrated ABUS or HHUS into MAM provided similar CDRs that were significantly higher than those for MAM alone in younger women (45-54 years) with denser breasts. ABUS has the potential to avoid unnecessary biopsies and provides specific image features to distinguish malignant tumors from HHUS.

Effects of sleep quality on suicide risk in COVID-19 patients: The chain mediating of anxiety and depressive symptoms.

Background: Although current studies have identified sleep disorders as an independent risk factor for suicide, the relationship between sleep disorders and suicide risk has not been well established. This study explored whether anxiety and depressive symptoms are used as mediators to participate in the impact of sleep quality on suicide risk. Methods: This is a cross-sectional study. We administered a psychological questionnaire to the participants, using a combination of self-assessment and psychiatrist assessment.Sleep quality, suicide risk, level of anxiety and depressive symptoms were assessed by PSQI, NGASR, SAS and SDS.The study subjects were 391 hospitalized COVID-19 patients from Wuhan hospitals. We used model 6 in the PROCESS (version 3.5) plug-in of SPSS software to conduct mediation test with sleep quality as the independent variable, suicide risk as the dependent variable, level of anxiety and depressive symptoms as intermediate variables. Results: The severity of anxiety and depressive symptoms and the risk of suicide in the sleep disorder group (63.15 ± 13.71, 59.85 ± 13.38, 6.52 ± 3.67) were higher than those in the non-sleep disorder group (49.83 ± 13.14, 44.87 ± 10.19, 2.87 ± 3.26) (P < 0.001). The mediation model works well, The total indirect effect was 0.22 (95%CI = [0.17, 0.28]), and the direct effect was 0.16 (95%CI = [0.08, 0.24]). Limitations: This study used a self-assessment scale. Conclusions: Anxiety and depressive symptoms played a chain mediating role between sleep quality and suicide risk.

Visualization of RNA Transcripts in Muscle Stem Cells Using Single-Molecule Fluorescence In Situ Hybridization.

Uncovering the transcriptomic signatures of quiescent muscle stem cells elicits the regulatory networks on stem cell quiescence. However, the spatial clues of the transcripts are missing in the commonly used quantitative analysis such as qPCR and RNA-seq. Visualization of RNA transcripts using single-molecule in situ hybridization provides additional subcellular localization clues to understanding gene expression signatures. Here, we provide an optimized protocol of smFISH analysis on Fluorescence-Activated Cell Sorting isolated muscle stem cells to visualize low-abundance transcripts.

Exogenous melatonin alleviates neuropathic pain-induced affective disorders by suppressing NF-κB/ NLRP3 pathway and apoptosis.

In this study, we aimed to evaluate the anti-inflammatory and anti-apoptotic effects of melatonin (MLT) on neuropathic pain (NP)-induced anxiety and depression in a rat model. Adult male rats were separated into four groups, i.e., Sham-VEH: healthy animals received a vehicle, Sham-MLT (10 mg/kg), and chronic constrictive injury (CCI)-VEH: nerve ligation received the vehicle, and CCI-MLT. Next, we used behavioral tests to evaluate pain severity, anxiety, and depression. Finally, rats were sacrificed for molecular and histopathological studies. Behavioral tests showed that NP could induce depressive- and anxiety-like behaviors. NP activated NF-κB/NLRP3 inflammasome pathways by upregulating NF-κB, NLRP3, ASC, active Caspase-1, also enhancing the concentrations of cytokines (IL-1ß and IL-18) in the prefrontal cortex (PFC) and hippocampus (HC). NP upregulated Bax, downregulated Bcl2, and increased cell apoptosis in the HC and PFC. The rats treated with MLT eliminated the effects of NP, as the reduced pain severity, improved anxiety- and depressive-like behaviors, ameliorated NF-κB/NLRP3 inflammasome pathways, and modulated levels of cytokines in the HC and PFC. MLT could promote cell survival from apoptosis by modulating Bax and Bcl2. Therefore, it might be inferred that its anti-inflammatory and anti-apoptotic properties mediate the beneficial effects of MLT in NP-induced affective disorders.

Targeting metabolic vulnerability in mitochondria conquers MEK inhibitor resistance in KRAS-mutant lung cancer

MEK is a canonical effector of mutant KRAS; however, MEK inhibitors fail to yield satisfactory clinical outcomes in KRAS-mutant cancers. Here, we identified mitochondrial oxidative phosphorylation (OXPHOS) induction as a profound metabolic alteration to confer KRAS-mutant non-small cell lung cancer (NSCLC) resistance to the clinical MEK inhibitor trametinib. Metabolic flux analysis demonstrated that pyruvate metabolism and fatty acid oxidation were markedly enhanced and coordinately powered the OXPHOS system in resistant cells after trametinib treatment, satisfying their energy demand and protecting them from apoptosis. As molecular events in this process, the pyruvate dehydrogenase complex (PDHc) and carnitine palmitoyl transferase IA (CPTIA), two rate-limiting enzymes that control the metabolic flux of pyruvate and palmitic acid to mitochondrial respiration were activated through phosphorylation and transcriptional regulation. Importantly, the co-administration of trametinib and IACS-010759, a clinical mitochondrial complex I inhibitor that blocks OXPHOS, significantly impeded tumor growth and prolonged mouse survival. Overall, our findings reveal that MEK inhibitor therapy creates a metabolic vulnerability in the mitochondria and further develop an effective combinatorial strategy to circumvent MEK inhibitors resistance in KRAS-driven NSCLC.

Deep brain stimulation in patients with Parkinson's disease at Hoehn-Yahr stage 2.5-5: a single-center long-term follow-up study / 中华神经医学杂志

Objective:To investigate the long-term clinical effect of deep brain stimulation (DBS) on patients with Parkinson's disease (PD) at Hoehn-Yahr stage 2.5-5 and the differences of clinical effect among patients at different Hoehn-Yahr stages.Methods:A total of 69 PD patients (7 at Hoehn-Yahr stage 2.5, 27 at stage 3, 31 at stage 4, and 4 at stage 5) accepted DBS in Department of Functional Neurosurgery, Affiliated Brain Hospital of Nanjing Medical University from May 2014 to December 2016 were selected for long-term follow-up observation at 60 months after DBS. Unified Parkinson's Disease Rating Scale (UPDRS) was evaluated in the "off" phase of the patients before DBS and the "off" phases of the drugs under DBS start-up and continuous treatment at 6, 12, 24, 36, 48 and 60 months after DBS, respectively; Parkinson's Quality of Life Questionnaire (PDQ-39) and levodopa equivalent dose (LED) data were collected before and 6, 12, 24, 36, 48 and 60 months after DBS. DBS parameters of the patients were collected at 12 months after DBS; the total stimulation power, single pulse average energy and large single pulse energy were calculated. The differences in UPDRS-III scores, PDQ-39 scores and LEDD in these patients before DBS and at different time points after DBS were compared; the differences in UPDRS-III and PDQ-39 scores at different time points after DBS and postoperative DBS parameters at 12 months after DBS in patients at different Hoehn-Yahr stages were compared.Results:Compared with those before DBS, the UPDRS-III scores, PDQ-39 scores and LED were significantly reduced at 6, 12, 24, 36, 48 and 60 months after DBS ( P<0.05). Significant differences in UPDRS-III scores were noted between patients at Hoehn-Yahr stage 5 and Hoehn-Yahr stage 2.5 and stage 3 at 12 and 24 months after DBS ( P<0.05); however, no significant differences in UPDRS-III scores were noted between patients at Hoehn-Yahr stage 5 and Hoehn-Yahr stage 4 at same time points ( P>0.05); and no significant differences in UPDRS-III scores were noted between patients at Hoehn-Yahr stage 5 and patients at Hoehn-Yahr stage 2.5, stage 3, and stage 4 at other time points ( P>0.05). No significant differences in PDQ-39 scores were noted between patients at different Hoehn-Yahr stages at 6, 12, 24, 36, 48, and 60 months after DBS ( P>0.05). No significant difference in total stimulation power, single pulse average energy or large single pulse energy was noted among patients at different Hoehn-Yahr stages at 12 months after DBS ( P>0.05). Conclusion:DBS is long-term effective in improving motor function and quality of life in PD patients at Hoehn-Yahr stage 2.5-5, and patients at Hoehn-Yahr stage 5 do not need higher DBS parameters to obtain similar clinical improved effects as patients at Hoehn-Yahr stage 2.5-4.

Research progress of oral allergy syndrome / 中华预防医学杂志

Oral allergy syndrome (OAS) is an IgE-mediated hypersensitivity. Patients with pollen allergy will experience oropharyngeal allergy after eating fresh fruits or vegetables containing homologous pathogenesis-related allergen, occasionally accompanied by systemic symptoms, it is a special type of food hypersensitivity in which respiratory allergens and food allergens are similar structurally and lead to the cross-reactivity. At present, there is little research and attention to it in China. To master the definition, epidemiological characteristics, pathological mechanism, diagnosis, prevention and treatment of OAS is very important to the prevention and control of OAS. This article reviews the research progress of OAS, providing reference and prevention basis for clinicians to improve the diagnosis and differential diagnosis of OAS.

Effect of transcutaneous electrical acupoint stimulation on postoperative gastrointestinal function in patients undergoing lumbar spinal surgery / 中华麻醉学杂志

Objective:To evaluate the effect of transcutaneous electrical acupoint stimulation (TEAS) on postoperative gastrointestinal function in the patients undergoing lumbar spinal surgery.Methods:Fifty patients of both sexes, aged 50-75 yr, with body mass index of 18.5-28.0 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅰor Ⅱ, undergoing elective lumbar spinal surgery under general anesthesia, were divided into 2 groups ( n=25 each) by a random number table method: control group (group C) and TEAS group. In group C, stimulating electrodes were placed at the non-acupoint parts of the limbs, but no electrical stimulation was applied. In group TEAS, bilateral Neiguan (PC6), Hegu (L14), Zusanli (ST36), Shangjuxu (ST37) and Xiajuxu (ST39) acupoints were stimulated using disperse-dense waves with a frequency of 2/100 Hz. The intensity of stimulation was the maximum current that patients could tolerate. Simulation lasting 30 min was performed once a day before induction of anesthesia and within 1-7 days after operation. The time to first flatus, time to first defecation, time for recovery of first bowel sounds and occurrence of abdominal distension were recorded. The occurrence and score of postoperative nausea and vomiting were recorded at 24, 48 and 72 h after operation. Peripheral venous blood samples were collected before operation and at 1 and 3 days after operation for determination of the concentrations of serum substance P and cholecystokinin before surgery and at 1 and 3 days after surgery using enzyme-linked immunosorbent assay. Results:Compared with group C, the time to first flatus, time to first defecation and time for recovery of first bowel sounds were significantly shortened, and the incidence of abdominal distension was decreased in group TEAS ( P<0.01). There was no significant difference in the incidence and score of postoperative nausea and vomiting and serum concentrations of substance P and cholecystokinin before surgery and at 1 and 3 days after surgery between the two groups ( P>0.05). Conclusions:TEAS can improve postoperative gastrointestinal function in the patients undergoing lumbar spinal surgery.

Exploration in the medication law and core TCM prescriptions of Jia Yuejin in the treatment of coronary heart disease complicated with depression based on the "target-component-Chinese materia medica" and clinical data / 国际中医中药杂志

Objective:To explore the medication law and core TCM prescriptions of Jia Yuejin in the treatment of coronary heart disease (CHD) complicated with depressive disorder (DD) by analyzing target-based network and mining clinical data.Methods:The targets of CHD complicated with DD were obtained by GeneCards, OMIM, TTD and other databases, and then the protein-protein interaction network of the two disease targets was constructed and then screened out the core targets. The Metascape platform was used to perform GO and KEGG pathway enrichment analysis on the intersection targets respectively to analyze the mechanism of action of CHD complicated with DD. Then TCMSP was used to query the active components acting on the targets and the Chinese materia medica containing these active components, and the data were imported into Cytoscape 3.9.0 to construct the core target-active component-Chinese materia medica network for network topology analysis. The outpatient clinical data of Jia Yuejin from January 1, 2015 to January 1, 2021 were collected, and data mining was conducted by using the Ancient and Modern Medical Case Cloud Platform (V2.3.5) to obtain his commonly used prescriptions. The results were fitted with the core TCM prescriptions obtained by target network analysis, and the drugs in the core prescriptions were analyzed.Results:Totally 1 501 intersection targets were obtained by protein interaction network analysis of CHD complicated with DD, which could be divided into 4 core target clusters, including inflammation cause, subclass tumor cause, subclass lipid metabolism factor, and fibrosis factor; a total of 480 active components were obtained by TCMSP, which belonged to 181 types of Chinese materia medica, including 8 core components: quercetin, kaempferol, luteolin, carotene, beta-carotene, acacetin, formononetin and ellagic acid. GO enrichment analysis yielded 61 results, mainly including positive regulation of protein phosphorylation, signal receptor agonist activity, side of membrane , etc.; KEGG pathway enrichment analysis yielded a total of 20 results, mainly including cancer pathways, lipid and atherosclerosis, JAK-STAT signaling pathway, etc. Clinical data mining included 120 cases and 148 prescriptions, including 135 types of Chinese materia medica; the properties were mainly mild, warm, slightly cold and cold; the tastes were mainly sweet, bitter and light, and the medicine mainly belongs to the lung, spleen, liver, heart, stomach, kidney and other meridians; drug association analysis, cluster analysis and complex network analysis were used to synthesize common prescriptions. The core TCM prescriptions obtained from common prescription and target network analysis were fitted: Pinelliae Rhizoma, Glycyrrhizae Radixet Rhizoma, Bupleuri Radix, Cyperi Rhizoma, Salviea Miltiorrhizae Radix et Rhizoma, Corydalis Rhizoma, Codonopsis Radix, Astragali Radix, Acori Tatarinowii Rhizoma. Conclusion:The medication law of Jia Yuejin in the treatment of CHD complicated with DD is in accordance with core TCM prescriptions. This study can provide guidance for clinical treatment and further research of CHD complicated with DD.