Mechanism of ellagic acid improving cognitive dysfunction in APP/PS double transgenic mice based on PI3K/AKT/GSK-3β signaling pathway / 中国药理学通报

Aim To investigate the effect of ellagic acid (EA) on cognitive function in APP/PS 1 double- transgenic mice, and to explore the regulatory mechanism of ellagic acid on the level of oxidative stress in the hippocampus of double-transgenic mice based on the phosphatidylinositol 3-kinase/protein kinase B/glycogen synthase kinase-3 (PI3K/AKT/GSK-3 β) signaling pathway. Methods Thirty-two SPF-grade 6-month-old APP/PS 1 double transgenic mice were randomly divided into four groups, namely, APP/PS 1 group, APP/PS1 + EA group, APP/PS1 + LY294002 group, APP/PS 1 + EA + LY294002 group, with eight mice in each group, and eight SPF-grade C57BL/6J wild type mice ( Wild type) were selected as the blank control group. The APP/PS 1 + EA group was given 50 mg · kg

Clinicopathological features of intravascular large B-cell lymphoma and collision tumors of five cases / 中华病理学杂志

Objective: To investigate the clinicopathological characteristics, diagnosis and differential diagnosis of intravascular large B-cell lymphoma (IVLBCL) and its collision tumors. Methods: Five cases of IVLBCL were collected, including 2 cases of collision tumors, and 1 case complicated with liver cirrhosis. The morphology and immunophenotype were analyzed. The related literature was reviewed. Results: There were 2 females and 3 males, aged from 53 to 73 years, with a median age of 65 years. The tumors were located in the lower extremities, right cerebellar hemisphere, left kidney, bilateral nasal cavity, and liver, respectively. Cases 2 and 3 were incidentally found in meningioma and renal cell carcinoma tissues, respectively. Case 5 had a background of liver cirrhosis. Morphologically, atypical large lymphoid cells were located in small blood vessels and capillary lumen, with little cytoplasm, hyperchromasia, prominent nucleoli, and obvious mitotic figures. Immunohistochemically, the IVLBCL tumor cells expressed CD20 and PAX5; 2 cases were CD5 positive. One of the 5 cases was GCB phenotype, and 4 cases were non-GCB phenotype. All cases expressed C-MYC (positive rate was 10%-40%). PD-L1 was positive in 4 cases (positive rate was 60%-90%). Ki-67 proliferation index was 70%-90%. CKpan, CD3, TDT, and CD34 were negative. In case 2, meningioma cells were positive for PR, EMA, and vimentin, but negative for CKpan and PD-L1. In case 3, renal carcinoma cells were positive for CKpan, PAX8, EMA, vimentin, CAⅨ and CD10, while PD-L1 was negative. No EBER expression (by in situ hybridization) or C-MYC gene translocation (FISH, break-apart probe) was detected in any of the 5 cases. Three patients were followed up, and all died within 1-13 months. Conclusions: IVLBCL is a highly aggressive lymphoma, with occult clinical manifestations and poor prognosis. Collision tumors of IVLBCL are extremely rare. A better understanding of IVLBCL would help pathologists avoid misdiagnoses.

Human ESC-derived vascular cells promote vascular regeneration in a HIF-1α dependent manner

Hypoxia-inducible factor (HIF-1α), a core transcription factor responding to changes in cellular oxygen levels, is closely associated with a wide range of physiological and pathological conditions. However, its differential impacts on vascular cell types and molecular programs modulating human vascular homeostasis and regeneration remain largely elusive. Here, we applied CRISPR/Cas9-mediated gene editing of human embryonic stem cells and directed differentiation to generate HIF-1α-deficient human vascular cells including vascular endothelial cells, vascular smooth muscle cells, and mesenchymal stem cells (MSCs), as a platform for discovering cell type-specific hypoxia-induced response mechanisms. Through comparative molecular profiling across cell types under normoxic and hypoxic conditions, we provide insight into the indispensable role of HIF-1α in the promotion of ischemic vascular regeneration. We found human MSCs to be the vascular cell type most susceptible to HIF-1α deficiency, and that transcriptional inactivation of ANKZF1, an effector of HIF-1α, impaired pro-angiogenic processes. Altogether, our findings deepen the understanding of HIF-1α in human angiogenesis and support further explorations of novel therapeutic strategies of vascular regeneration against ischemic damage.

Targeting ferroptosis and ferritinophagy: new targets for cardiovascular diseases / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Cardiovascular diseases (CVDs) are a leading factor driving mortality worldwide. Iron, an essential trace mineral, is important in numerous biological processes, and its role in CVDs has raised broad discussion for decades. Iron-mediated cell death, namely ferroptosis, has attracted much attention due to its critical role in cardiomyocyte damage and CVDs. Furthermore, ferritinophagy is the upstream mechanism that induces ferroptosis, and is closely related to CVDs. This review aims to delineate the processes and mechanisms of ferroptosis and ferritinophagy, and the regulatory pathways and molecular targets involved in ferritinophagy, and to determine their roles in CVDs. Furthermore, we discuss the possibility of targeting ferritinophagy-induced ferroptosis modulators for treating CVDs. Collectively, this review offers some new insights into the pathology of CVDs and identifies possible therapeutic targets.

Relationship Between Signaling Pathway and Diabetic Retinopathy and Intervention of Traditional Chinese Medicine： A Review / 中国实验方剂学杂志

Diabetic retinopathy （DR） is one of the most common chronic microvascular complications of diabetes mellitus. It has a high rate of blindness， and the age of onset is gradually getting younger， which seriously affects the physical and mental health and quality of life of patients. The disease is retinal damage induced by diabetes mellitus， which is a kind of fundus disease with the main manifestations of fundus hemorrhage， hard exudation， microhemangioma， cotton-wool spots， neovascularization， etc. In traditional Chinese medicine （TCM）， it is classified into the category of "diabetic cataracts" and other diseases. At present， there is no effective method to prevent the progress of the disease in modern medicine， so it is particularly important to choose a reasonable and effective intervention to prevent and treat DR. Studies have confirmed that TCM has unique advantages in the treatment of DR. It can use its advantages of multiple bioactive components， multiple targets， and multiple pathways to intervene in the development process of DR from various aspects. By searching for the relevant literature on the progress of the intervention of DR with TCM monomers and compounds， this paper mainly reviews the relevant research results of the treatment of DR with multiple signaling pathways such as phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）， nuclear factor kappa-B（NF-κB）， p38 mitogen-activated protein kinase （p38 MAPK）， nuclear factor erythroid 2-related factor （Nrf2）/hemeoxygenase-1 （HO-1）， Hippo， advanced glycation end products （AGEs）/receptor for advanced glycation end products （RAGE）， and Akt/glycogen synthase kinase-3β （GSK-3β）， so as to provide more ideas and directions for the clinical prevention and treatment of DR.

Non-targeted LC-MS profiling reveals association between human early embryo grades and levels of amino acids and carnitines in embryo culture medium / 中华检验医学杂志

Objective:In order to determine the development potential of human embryos in vitro, amino acid and carnitine levels were measured in the culture medium of different grades of early human embryos. Methods:From the infertile couples who received in vitro fertilization-embryo transfer treatment in the Department of Reproductive Medicine of Linyi People′s Hospital from June 2022 to December 2022, the age of the women was defined as 25-35 years old [31.5(26.5, 33.25)] with 8-20 eggs, 126 cultured cells and embryos of the third day were randomly collected from infertile couples. They were divided into three groups according to the morphological level of the corresponding embryos: excellent, neutral and poor. Amino acids and L-carnitines levels in culture medium were detected by liquid chromatography-mass spectrometry (LC-MS). Using analysis of variance to compare differences among groups, correlation analysis, factor analysis was performed to analyze the association between the levels of amino acids and L-carnitines and development potential of early human embryos.Results:The value of Methionine/Phenylalanine was found statistically different among superior embryo (3.09±1.67), moderate embryo (4.00±1.19) and inferior embryo (4.99±2.04). The difference between the three groups was statistically different ( F=7.09, P<0.05): superior embryo vs moderate embryo ( t=-0.91, P<0.05), superior embryo vs inferior embryo ( t=-1.91, P<0.05), moderate embryo vs inferior embryo ( t=-0.99, P<0.05). Among different amino acids, Phe had the strongest positive correlation with Tyr ( r=0.99, P<0.01). Among different carnitines, C 8/C 10 has the strongest positive correlation with C 5DC+C 6OH/C 16( r=0.44, P<0.01). The weight value of leucine (isoleucine), arginine, valine/phenylalanine, glycine, tyrosine and carnitine(C 5DC+C 6OH)/C 8 calculated by the least square fitting model is 2.22, 1.99, 1.65, 1.54, 1.21 and 1.15 respectively. Conclusion:Leucine, arginine, valine/phenylalanine, glycine, tyrosine and carnitine (C 5DC+C 6OH)/C 8 in embryo culture medium were significantly correlated with the levels of early human embryos in vitro.

Analysis of clinical and pathological characteristics in patients with type 2 diabetes mellitus complicated with renal damage / 中华肾脏病杂志

It was a retrospective study. The patients with type 2 diabetes mellitus (T2DM) who underwent renal biopsy in the Department of Nephrology, the First Affiliated Hospital of Xi'an Jiaotong University from 2015 to 2021 were enrolled to analyze the pathological and clinical manifestations of kidney. There were 483 patients enrolled, including 136 patients who had no history of diabetes mellitus, newly diagnosed as T2DM according to an oral glucose tolerance test. The age was (52.80±13.13) years old. There were 337 males (69.77%). Based on the renal biopsy, the patients were classified as diabetic kidney disease (DKD, 22.15%, 107/483), DKD+non-diabetic kidney disease (NDKD)(6.63%, 32/483), and NDKD (71.22%, 344/483). Membranous nephropathy was the most common pathology in patients with NDKD (40.41%, 139/344) and DKD+NDKD (34.38%, 11/32). In the 136 newly diagnosed T2DM patients, there were 3 patients (2.21%) with DKD, 2 patients (1.47%) with DKD+NDKD, and 131 patients with NDKD (96.32%). The proportions of DKD in patients with diabetes history ≤3 months, 3-12 months, 1-5 years, 5-10 years and ≥10 years were 10.53% (6/57), 25.00% (16/64), 26.53% (26/98), 41.56% (32/77) and 47.06% (24/51), respectively. The proportions of DKD+NDKD in patients with diabetes history ≤3 months, 3-12 months, 1-5 years, 5-10 years and ≥10 years were 3.51% (2/57), 3.13% (2/64), 10.20% (10/98), 9.09% (7/77) and 17.65% (9/51), respectively. Multivariate logistic regression analysis results showed that, the duration of diabetes history ( OR=1.130, 95% CI 1.057-1.208, P<0.001), diabetes retinopathy ( OR=12.185, 95% CI 5.331-27.849, P<0.001), urinary red blood cell count ( OR=0.987, 95% CI 0.974-0.999, P=0.039), glycosylated hemoglobin ( OR=1.482, 95% CI 1.119-1.961, P=0.006) as well as hemoglobin ( OR=0.973, 95% CI 0.957-0.990, P=0.001) were independently correlated with DKD. The proportions of DKD and DKD+NDKD increase with the prolongation of diabetes history. Membranous nephropathy is the most common pathology in NDKD and DKD+NDKD patients. Even in patients newly diagnosed with T2DM, it is necessary to screen for DKD. The duration of diabetes history, diabetes retinopathy, urinary red blood cell count, glycosylated hemoglobin and hemoglobin may be used to identify DKD from NDKD.

Effect of Mongolian medicine Eerdun Wurile on postoperative cognitive function in elderly patients undergoing thoracoscopic lobectomy / 中华麻醉学杂志

Objective:To evaluate the effect of Mongolian medicine Eerdun Wurile on postoperative cognitive function in elderly patients undergoing thoracoscopic lobectomy.Methods:Sixty elderly patients of either gender, aged ≥60 yr, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, with body mass index≤28 kg/m 2, with preoperative Mini-Mental State Examination (MMSE) score ≥27 points, undergoing thoracoscopic lobectomy under general anesthesia, were divided into 2 groups ( n=30 each) using the random number table method: control group (group C) and Eerdun Wurile group (group E). Eerdun Wurile 15 capsules per day were taken for 7 consecutive days starting from 3 days before surgery in group E, and placebo was given instead in group C. The peripheral venous blood samples were collected before medication at 3 days before surgery (T 1) and 24 and 72 h after surgery (T 2, 3) for determination of the concentrations of serum brain-derived neurotrophic factor (BDNF), interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and Tau proteins by enzyme-linked immunosorbent assay. The patients′ cognitive function was assessed by MMSE at T 1 and 5 days after surgery (T 4), and the occurrence of cognitive decline (MMSE score < 27) was recorded. Results:Compared with group C, the serum BDNF concentration was significantly increased at T 2 and T 3, and the concentrations of IL-1β, TNF-α and Tau protein were decreased, the MMSE score was increased at T 4, and the incidence of cognitive decline was decreased in group E ( P<0.05). Conclusions:Mongolian medicine Eerdun Wurile can improve postoperative cognitive function in elderly patients undergoing thoracoscopic surgery, and the mechanism may be related to reduction of systemic inflammatory responses and promotion of nerve cell repair and regeneration.

Neck contour changes and relevant factors in nasopharyngeal carcinoma patients treated with helical tomotherapy / 中华放射肿瘤学杂志

Objective:To study the change pattern of neck diameter and relevant factors in nasopharyngeal carcinoma (NPC) patients treated with helical tomotherapy, aiming to provide reference for clinical practice.Methods:Fifteen NPC patients treated with helical tomotherapy at Sun Yat-Sen University Cancer Center from November 2020 to February 2021 were enrolled in this study. The transverse diameters of NPC patients' neck contours and body weight of all patients during radiotherapy were recorded weekly. We used descriptive statistics to explore the distribution of transverse diameters of NPC patients' neck contours during radiotherapy. And Spearman correlation analysis was used to assess the association between weight loss and changes in neck contour transverse diameter.Results:During radiotherapy, the distribution of transverse diameters of NPC patients' neck contours was completely different from the initial values. Specifically, the transverse diameters were significantly reduced at the 4th week of the radiotherapy. Moreover, the reduction of transverse diameter of neck contour was highly correlated with the weight loss ( r=0.803, P<0.05), and moderately correlated with gender ( r=0.523, P<0.05). However, there was no statistical correlation between the alteration of neck diameter and age, TNM stage, and the mean dose of GTV nd-L, GTV nd-R, PTV nd-L and PTV nd-R (all P>0.05). Conclusions:The neck contours of NPC patients are altered regularly during helical tomotherapy, which are narrowed the most obviously in the 4th week. Extensive attention should be paid to the changes of neck contour during radiotherapy in clinical practice.

Expert consensus on perioperative nursing management of nutrition for elderly patients with hip fractures (version 2023) / 中华创伤杂志

Hip fractures are among the most common fractures in the elderly, presenting to be a leading cause of disability and mortality. Surgical treatment is currently the main treatment method for hip fractures. The incidence of perioperative malnutrition is increased after hip fractures in the elderly due to the comorbidities, decreased basal metabolic rate, accelerated protein breakdown, weakened anabolism and surgical stress. However, malnutrition not only increases the incidence of postoperative complications, but also leads to increased mortality, indicating an important role of perioperative nursing management of nutrition for the elderly patients with hip fractures. At present, there still lacks scientific guidance and application standards on perioperative nursing management of nutrition for the elderly patients with hip fractures. Therefore, the Orthopedic Nursing Committee of Chinese Nursing Association and the Editorial Board of Chinese Journal of Trauma organized relevant experts to formulate the Expert consensus on perioperative nursing management of nutrition for elderly patients with hip fractures ( version 2023) according to evidence-based medical evidences and their clinical experiences. Fourteen recommendations were made from aspects of nutrition screening, nutrition assessment, nutrition diagnosis, nutrition intervention and nutrition monitoring to provide guidance for perioperative nursing management of nutrition in elderly patients with hip fractures.

Predictive value of HACOR score on the clinical outcome of non-invasive positive pressure ventilation in the treatment of chronic obstructive pulmonary disease with pulmonary encephalopathy / 中华危重病急救医学

Objective:To explore the predictive value of HACOR score [heart rate (H), acidosis (A), consciousness (C), oxygenation (O), and respiratory rate (R)] on the clinical outcome of non-invasive positive pressure ventilation in patients with pulmonary encephalopathy due to chronic obstructive pulmonary disease (COPD).Methods:A prospective study was conducted. The patients with COPD combined with pulmonary encephalopathy who were admitted to Henan Provincial People's Hospital from January 1, 2017 to June 1, 2021 and initially received non-invasive positive pressure ventilation were enrolled. Besides non-invasive positive pressure ventilation, standard medical treatments were delivered to these patients according to guidelines. The need for endotracheal intubation was judged as failure of non-invasive ventilation treatment. Early failure was defined as the need for endotracheal intubation within 48 hours of treatment, and late failure was defined as the need for endotracheal intubation 48 hours and later. The HACOR score at different time points after non-invasive ventilation, the length of intensive care unit (ICU) stay, the total length of hospital stay, and the clinical outcome were recorded. The above indexes of patients with non-invasive ventilation were compared between successful and failed groups. The receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive effect of HACOR score on the failure of non-invasive positive pressure ventilation in the treatment of COPD with pulmonary encephalopathy.Results:A total of 630 patients were evaluated, and 51 patients were enrolled, including 42 males (82.35%) and 9 females (17.65%), with a median age of 70.0 (62.0, 78.0) years old. Among the 51 patients, 36 patients (70.59%) were successfully treated with non-invasive ventilation and discharged from the hospital eventually, and 15 patients (29.41%) failed and switched to invasive ventilation, of which 10 patients (19.61%) were defined early failure, 5 patients (9.80%) were late failure. The length of ICU and the total length of hospital stay of the non-invasive ventilation successful group were significantly longer than those of the non-invasive ventilation failure group [length of ICU stay (days): 13.0 (10.0, 16.0) vs. 5.0 (3.0, 8.0), total length of hospital stay (days): 23.0 (12.0, 28.0) vs. 12.0 (9.0, 15.0), both P < 0.01]. The HACOR score of patients at 1-2 hours in the non-invasive ventilation failure group was significantly higher than that in the successful group [10.47 (6.00, 16.00) vs. 6.00 (3.25, 8.00), P < 0.05]. However, there was no significant difference in HACOR score before non-invasive ventilation and at 3-6 hours between the two groups. The ROC curve showed that the area under the ROC curve (AUC) of 1-2 hour HACOR score after non-invasive ventilation for predicting non-invasive ventilation failure in COPD patients with pulmonary encephalopathy was 0.686, and the 95% confidence interval (95% CI) was 0.504-0.868. When the best cut-off value was 10.50, the sensitivity was 60.03%, the specificity was 86.10%, positive predictive value was 91.23%, and negative predictive value was 47.21%. Conclusions:Non-invasive positive pressure ventilation could prevent 70.59% of COPD patients with pulmonary encephalopathy from intubation. HACOR score was valuable to predict non-invasive positive pressure ventilation failure in pulmonary encephalopathy patients due to COPD.

Current main problems and countermeasures for prevention and control of endemic diseases in China / 中华地方病学杂志

Over the past decade, remarkable progress has been made in prevention and control of endemic diseases in China through implementation of the 12th and the 13th Five-Year National Plans for Prevention and Control of Endemic Diseases and the Three-Year Action Plan for Special Prevention and Control of Endemic Diseases. Based on the latest monitoring data of endemic diseases and the evaluation results of the control and elimination of endemic diseases of the 13th Five-Year Plan, this paper analyzed current main problems in prevention and control of endemic diseases in China, focusing on implementation of prevention and control measures for iodine deficiency disorders, endemic fluorosis, and endemic arsenicosis, as well as the treatment and management of patients. Accordingly, corresponding countermeasures and suggestions are put forward from three aspects, including prevention and control mechanism, implementation of prevention and control measures, and scientific research, so as to provide scientific basis for the country and various regions to consolidate the achievements of prevention and control of endemic diseases and accurately implement the prevention and control measures of endemic diseases.

Comparison of detection rates and time costs of different fundus imaging techniques for retinal neovascularization in optic disc and other area of proliferative diabetic retinopathy / 中华实验眼科杂志

Objective:To compare the detection rate and time cost of different imaging methods for retinal and optic disc neovascularization in proliferative diabetic retinopathy (PDR).Methods:A cross-sectional study was conducted.Thirty-eight patients (48 eyes) with PDR were enrolled in Henan Eye Hospital from October 2019 to February 2021, including 22 males (28 eyes) and 16 females (20 eyes). The average age of the patients was (51.08±13.35) years.All patients underwent ultra-widefield imaging (UWFI), fundus fluorescein angiography (FFA), optical coherence tomography angiography (OCTA), en face optical coherence tomography (OCT), near-infrared fundus imaging (IR) combined with spectral domain OCT (SD-OCT). Wide field swept-source OCTA (WF-SS-OCTA) was performed in the patients who were unsuitable for FFA.The time required for each examination in one eye and the detection rate of neovascularization at the optic disc (NVD) and retinal neovascularization elsewhere (NVE) were recorded.This study adhered to the Declaration of Helsinki.The study protocol was approved by Henan Eye Hospital (No.HNEECKY-2021[22]). All patients were informed about the method and purpose of the study and voluntarily signed the informed consent form.Results:The mean monocular examination time costs of UWFI, IR+ SD-OCT, OCTA+ en face OCT, FFA and WF-SS-OCT was (0.51±0.13), (2.08±0.57), (5.79±0.68), (17.66±1.83) and (13.38±1.23)min, respectively.There was a significant overall difference in the mean monocular examination time among the five methods ( F=2 077.960, P<0.001). The detection rates of UWFI, IR+ SD-OCT, OCTA+ en face OCT, FFA+ WF-SS-OCT for NVE and NVD were 52.1%(25/48) and 12.5%(6/48), 81.3%(39/48) and 20.8%(10/48), 83.3%(40/48) and 27.1%(13/48), 93.8%(45/48) and 29.2%(14/48), respectively.There were significant differences in the detection rates of NVE ( χ2=26.460, P<0.001) but not in the detection rates of NVD ( χ2=4.645, P=0.200) among the various methods.Five neovascular buds were detected by OCTA in 3 eyes, but not by FFA. Conclusions:UWFI and IR+ SD-OCT are faster and non-invasive methods for the screening of NVD and NVE in PDR eyes.Compared with FFA, OCTA and en face OCT can show the shape of neovascularization more clearly.FFA provides a wide-range retinal image, but it is time-consuming and invasive.WF-SS-OCTA extends the examination range of OCTA and detects neovascularization non-invasively and faster than FFA.

The curative effect of Tongdu Tiaoshen acupuncture on hemiplegia after stroke and its influence on nerve function and limb function / 国际中医中药杂志

Objective:To explore the application of Tongdu Tiaoshen acupuncture in patients with hemiplegia after stroke.Methods:Randomized controlled trial. A total of 70 patients who met the inclusion criteria for post-stroke hemiplegia in our hospital from January 2020 to December 2021 were divided into two groups, with 35 cases in each group, according to the random number table. The control group was given conventional treatment combined with rehabilitation exercise therapy, and the observation group was given Tongdu Tiaoshen acupuncture on the basis of the above, and both groups were treated continuously for 1 month. Compare of the two groups Fugl-Meyer Assessment (FMA), Modified Ashworth Scale (MAS), National Institutes of Health Stroke Scale (NIHSS), Activity of Daily Living (ADL) score; Brunnstrom stage method was used to assess the patient's motor ability, and Holden walking function grade was used to assess the patient's walking ability. The activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time(TT), and serum fibrinogen (FIB), D-dimer (D-D), plasminogen activator inhibitor 1 (PAI-1) levels were observed by ELISA. Adverse events were recorded and clinical efficacy was evaluated.Results:The total effective rates of the observation group and the control group were 97.14% (34/35) and 77.14% (27/35), respectively, and the difference between the two groups was statistically significant ( χ2=6.25, P=0.012). After treatment, the scores of FMA and ADL in the observation group were significantly higher than those in the control group ( t values were 9.23 and 9.54, respectively, P<0.01), the MAS and NIHSS scores were significantly lower than those in the control group ( t values were 10.23 and 11.97, respectively, P<0.01). After treatment, the distribution of patients in Brunnstrom stage Ⅴ and Ⅵand Holden functional walking stage Ⅳ and Ⅴ in the observation group was significantly higher than those in the control group ( χ2 values were 11.96 and 11.27, respectively, P<0.05). After treatment, APTT, PT and TT in the observation group were significantly longer than those in the control group ( t values were 10.37, 13.57 and 6.54, respectively, P<0.01); serum FIB, D-D and PAI-1 levels were significantly lower than those in the control group ( t values were 12.85, 11.94 and 27.39, respectively, P<0.01). No adverse reactions occurred in both groups. Conclusion:The treatment of post-stroke hemiplegia with Tongdu Tiaoshen acupuncture can improve the effect of clinical treatment and the ability of daily life, neurological function, limb function, movement and walking ability, and stabilize the clotting state.

Zisheng Pill Formula （资生丸方） in Treating Malignant Tumor Targeted Therapy-induced Diarrhea with Spleen-stomach Weakness Syndrome：A Randomized-controlled Trial / 中医杂志

ObjectiveTo evaluate the clinical efficacy and safety of Zisheng Pill Formula （资生丸方， ZPF） in the treatment of malignant tumor targeted drugs-related diarrhea with spleen-stomach weakness syndrome. MethodsThis was an randomized controlled study， involving 34 cases in the treatment group and 33 cases in the control group. The treatment group was given ZPF decoction， one dose daily by twice， 200 ml each time， while the control group was given montmorillonite powder， three times per day， 3 g each time， with the first dose doubled， both groups for two weeks. The diarrhea frequency， stool characteristics， common terminology criteria for adverse events （CTCAE） for diarrhea， traditional Chinese medicine （TCM） syndrome score， the European organization for research on treatment of cancer （EORTC） quality of life questionnaire （EORTC QOL-C30） score， levels of serum intestinal functional indicators including diamine oxidase （DAO）， D-lactic acid （D-LA）， endotoxin （ET） levels were evaluated before and after treatment， and the safety was assessed. ResultsThere were 33 cases in the treatment group and 32 cases in the control group in terms of the per-protocol set （PPS）. The total effective rate of diarrhea of the treatment group and control group was 84.85% and 37.50%， respectively， and the total effective rate of TCM syndromes was 93.94% and 34.38%， with statistically significant differences between the groups （P＜0.01）. After treatment， the frequency of diarrhea and CTCAE grade decreased in both groups， with improved stool characteristics， increased overall health score， and decreased DAO， D-LA and ET levels； in the treatment group， the frequency of diarrhea， the TCM symptom scores in terms of stool characteristics， fear of cold and cold limbs， fatigue， numbness， nausea and vomiting， abdominal distension and abdominal pain were reduced， while the physical function score increased； in the control group， the frequency of diarrhea， stool characteristics and abdominal pain score decreased （P＜0.05 or P＜0.01）. The results favored the treatment group than the control group in all the outcomes except for the nausea and vomiting score， abdominal pain score， overall health score， physical function score， and ET level （P＜0.05 or P＜0.01）. During the treatment， one case of gastrointestinal infection and one case of constipation occurred in the treatment group， while one case of tumor progression in the control group. ConclusionZPF can effectively improve the clinical symptoms， increase quality of life， decrease serum DAO， D-LA and ET levels， and is safe when treating malignant tumor targeted drug-related diarrhea with spleen-stomach weakness syndrome. The possible mechanism may be related to the repair of intestinal mucosa barrier function.

Studies on orally disintegrating tablet of diphenhydramine hydrochloride and caffeine / 药学实践杂志

Objective To optimize the formulation and preparation of diphenhydramine hydrochloride and caffeine orally disintegrating tablet. Methods Melt granulation technology of steric acid and API was used to mask the unpleasant tasting of diphenhydramine hydrochloride. The tablets were prepared by direct pressing the dry powder with CCMC-Na as disintegrating agent. The formulation was optimized by orthogonal experiments to achieve the shortest disintegration time and the best taste correction. Results The optimized formula of orally disintegrating tablet was as follows： diphenhydramine hydrochloride 25 mg, caffeine 60 mg, stearic acid 25 mg, aspatan 40 mg, blueberry essence 7 mg, mannitol 45 mg, MCC 210 mg, CCMC-NA 25 mg, SDS 8 mg and magnesium stearate 5 mg. Conclusion This preparation method for orally disintegrating tablet of diphenhydramine hydrochloride and caffeine is practical and easy for quality control.

Research progress in the evaluation of glymphatic system function by the DTI-ALPS method / 中南大学学报(医学版)

The glymphatic system can remove metabolic wastes from the brain, which plays a significant role in maintaining the homeostasis of the central nervous system. It is an important basis for advanced cognitive functions such as learning and memory. Studies have analyzed the function of glymphatic system by diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) recently. Compared with other invasive examinations that require fluorescent tracer technique or the injection of contrast agents, DTI-ALPS can evaluate the hydromechanics of the glymphatic system via quantifying the diffusion rate of water molecules in different directions, which turns out to be a non-invasive in vivo neuroimaging method. The ALPS-index calculated by the DTI-ALPS method is significantly correlated with the cognitive function in diseases of central nervous system and other system and can reflect the dynamic changes of diseases. In general, ALPS-index is expected to become a novel neuroimaging biomarker for predicting prognosis and clinical effects.

The role of methylation of placental glucocorticoid response gene in the association between pregnancy-related anxiety in the third trimester and birth outcomes / 中华预防医学杂志

Objective: To investigate the role of methylation of placental glucocorticoid response gene in the association between pregnancy-related anxiety in the third trimester and birth outcomes. Methods: Based on a prospective cohort study, singleton live births and their mothers from the Ma'anshan Birth Cohort Study (MABC) were included as participants in this study. The maternal pregnancy-related anxiety symptoms in the third trimester of pregnancy were evaluated by using the Pregnancy-related Anxiety Questionnaire. The neonatal birth outcomes were collected from medical records. The placental tissues from 300 pregnant women with pregnancy-related anxiety and 300 without pregnancy-related anxiety were collected to detect the methylation of FKBP5, NR3C1 and HSD11B2 genes using the Methyl Target approach. The methylation factors were extracted by exploratory factor analysis. Linear regression or logistic regression models were used to analyze the association between pregnancy-related anxiety in the third trimester, methylation factor scores, and birth outcomes. The mediating role of methylation factors in the association between pregnancy-related anxiety in the third trimester and birth outcomes was analyzed by using the Process procedure. Results: The mean age of 2 833 pregnant women was (26.60±3.60) years old. After adjusting for confounding factors, pregnancy-related anxiety in the third trimester increased the risk of small-for-gestational-age (OR=1.32, 95%CI:1.00-1.74). A total of 5 methylation factors were extracted, and the factor 5 was loaded with FKBP5 CpGs 18-21. Pregnancy-related anxiety in the third trimester was negatively correlated with the factor 5 (β=-0.24,95%CI:-0.44--0.05). The factor 5 was positively correlated with the gestational age (β=0.17, 95%CI:0.06-0.27). In addition, the factor 2 (β=0.02,95%CI:0.00-0.04) and factor 3 (β=0.03,95%CI:0.01-0.05) were positively correlated with 5-min Apgar score after delivery. However, this study did not found the mediating role of the scores of the factor characterized by FKBP5 in the relationship between pregnancy-related anxiety and birth outcomes. Conclusion: Pregnancy-related anxiety in the third trimester may reduce the methylation level of FKBP5 CpGs 18-21 in placental tissues and is associated with the risk of small-for-gestational-age.

Rac1 promotes the formation of heterotypic cell-in-cell structure / 生物工程学报

Heterotypic cell-in-cell structures (heCICs) are closely related to tumor development and progression, and have become a new frontier in life science research. Ras-related C3 botulinum toxin substrate 1 (Rac1) belongs to the classic Rho GTPase, which plays a key role in regulating the cytoskeleton and cell movement. To investigate the role and mechanism of Rac1 in the formation of heCICs, tumor cells and immune killer cells were labeled with cell-tracker, respectively, to establish the heCICs model. Upon treatment with the Rac1 inhibitor NSC23766, the formation of heCICs between tumor and immune cells was significantly reduced. The plasmid pQCXIP-Rac1-EGFP constructed by gene cloning was packaged into pseudoviruses that subsequently infect tumor cells to make cell lines stably expressing Rac1. As a result, the formation of heCICs was significantly increased upon Rac1 overexpression. These results demonstrated a promotive role of Rac1 in heCICs formation, which may facilitate treating cell-in-cell related diseases, such as tumors, by targeting Rac1.

Integrative pan-cancer analysis of cuproplasia-associated genes for the genomic and clinical characterization of 33 tumors / 中华医学杂志(英文版)

BACKGROUND@#The molecular mechanisms driving tumorigenesis have continually been the focus of researchers. Cuproplasia is defined as copper-dependent cell growth and proliferation, including its primary and secondary roles in tumor formation and proliferation through signaling pathways. In this study, we analyzed the differences in the expression of cuproplasia-associated genes (CAGs) in pan-cancerous tissues and investigated their role in immune-regulation and tumor prognostication.@*METHODS@#Raw data from 11,057 cancer samples were acquired from multiple databases. Pan-cancer analysis was conducted to analyze the CAG expression, single-nucleotide variants, copy number variants, methylation signatures, and genomic signatures of micro RNA (miRNA)-messenger RNA (mRNA) interactions. The Genomics of Drug Sensitivity in Cancer and the Cancer Therapeutics Response Portal databases were used to evaluate drug sensitivity and resistance against CAGs. Using single-sample Gene Set Enrichment Analysis (ssGSEA) and Immune Cell Abundance Identifier database, immune cell infiltration was analyzed with the ssGSEA score as the standard.@*RESULTS@#Aberrantly expressed CAGs were found in multiple cancers. The frequency of single-nucleotide variations in CAGs ranged from 1% to 54% among different cancers. Furthermore, the correlation between CAG expression in the tumor microenvironment and immune cell infiltration varied among different cancers. ATP7A and ATP7B were negatively correlated with macrophages in 16 tumors including breast invasive carcinoma and esophageal carcinoma, while the converse was true for MT1A and MT2A . In addition, we established cuproplasia scores and demonstrated their strong correlation with patient prognosis, immunotherapy responsiveness, and disease progression ( P  <0.05). Finally, we identified potential candidate drugs by matching gene targets with existing drugs.@*CONCLUSIONS@#This study reports the genomic characterization and clinical features of CAGs in pan-cancers. It helps clarify the relationship between CAGs and tumorigenesis, and may be helpful in the development of biomarkers and new therapeutic agents.