ObjectiveTo evaluate the effects of Tongnaoyin on the blood-brain barrier status and neurological impairment in acute ischemic stroke （AIS） patients with the syndrome of phlegm-stasis blocking collaterals by dynamic contrast-enhanced magnetic resonance imaging （DCE-MRI）. MethodsA total of 63 patients diagnosed with AIS in the Jiangsu Province Hospital of Chinese Medicine from October 2022 to December 2023 were enrolled in this study. According to random number table method，the patients were assigned into a control group （32 cases） and an observation group （31 cases）. The control group received conventional Western medical treatment，and the observation group took 200 mL Tongnaoyin after meals，twice a day from day 2 of admission on the basis of the treatment in the control group. After 7 days of treatment，the patients were examined by DCE-MRI. The baseline data for two groups of patients before treatment were compared. The National Institute of Health Stroke Scale （NIHSS） score and modified Rankin Scale （mRS） score were recorded before treatment and after 90 days of treatment for both groups. The rKtrans，rKep，and rVe values were obtained from the region of interest （ROI） of the infarct zone/mirror area and compared between the two groups. ResultsThere was no significant difference in the NIHSS or mRS score between the two groups before treatment. After 90 days of treatment，the NIHSS and mRS scores declined in both groups，and the observation group had lower scores than the control group （P<0.05）. After treatment，the rKtrans and rVe in the observation group were lower than those in the control group （P<0.01）. ConclusionCompared with conventional Western medical treatment alone，conventional Western medical treatment combined with Tongnaoyin accelerates the repair of the blood-brain barrier in AIS patients，thereby ameliorating neurological impairment after AIS to improve the prognosis.

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.
Humans ; Vascular Endothelial Growth Factor A/metabolism* ; Endothelial Cells/metabolism* ; Transcription Factors/metabolism* ; Gene Expression Regulation ; Hypoxia/metabolism* ; Cell Hypoxia/physiology*

Based on the data of a national sampling survey, this paper described and analyzed the understanding, attitude, behavior, and their differences and influencing factors of Chinese medical researchers on ethical review of biomedical research involving human subject. The survey found that researchers with master’s degree or below, working in scientific research institutes or universities, no overseas experience, living in the central region and not serving as committee members have relatively poor acquaintance of "ethical review" ; researchers with the characteristics of male, the younger age, living in the western region, knowing less about "ethical review" , agree more with the view that "ethical review consumes too much time and energy" ; researchers who serve as members of the ethics committee are more likely to participate in scientific research projects that have not passed the ethical review process. Therefore, recommendations are put forward: comprehensively popularizing the training of ethical review, focusing on strengthening the vulnerable groups and regions, strictly implementing ethical review laws and regulations, and strengthening evaluation and supervision, so as to improve the service quality and efficiency of ethical review in multiple directions.

Da Chaihutang from the Treatise on Febrile Disease （Shanghanlun） has the function of harmonizing lesser Yang and discharging internal heat. It is formulated by ZHANG Zhongjing for the concurrent diseases of lesser Yang and Yang brightness and has been widely used in the treatment of digestive system diseases， especially malignant tumors. By review of the articles published in the last 20 years， this paper summarizes the application of Da Chaihutang in treating digestive system tumors from syndrome analysis， clinical research， and mechanism research. Da Chaihutang can treat the syndrome involving lesser Yang and Yang brightness in the digestive system， release interior and exterior to expel pathogen， and remove obstruction by conforming to the descending nature of the six fu-organs. In clinical practice， Da Chaihutang can directly treat digestive system malignant tumors such as liver cancer， pancreatic cancer， intestinal cancer， gastric cancer， and gallbladder cancer. In addition， it can relieve common complications of digestive system malignant tumors， such as cancerous fever， malignant obstructive jaundice， and constipation. Moreover， it can alleviate the adverse reactions caused by Western medical treatment， such as post-embolization syndrome， side effects of chemotherapy， and incomplete postoperative obstruction. Da Chaihutang is effective when used alone as it can relieve clinical symptoms， improve prognosis， and prolong survival of advanced patients and is safe and non-toxic， suitable for long-term use by tumor patients. Regarding the mechanism， Da Chaihutang can promote the apoptosis and inhibit the proliferation of tumor cells， reduce inflammation and inflammatory injury， and improve the liver function. The clear effect and mechanism confirms the anti-tumor effect of Da Chaihutang. This paper comprehensively describes the current research status of Da Chaihutang in the treatment of digestive system tumors and puts forward the deficiencies and improvement measures for the current research， aiming to provide reference for the application of this formula in treating digestive system tumors， the establishment of Chinese and Western medicine treatment schemes of tumors， and the research and development of anti-tumor drugs.

Objective To explore the possible effects and the underlying molecular mechanisms of xueshuantong[The main active component is panax notoginseng(PNS)]on the cognitive function and neural excitability of mice with Alzheimer's disease(AD).Methods The APP/PS1 mice were used as an animal model for AD research,at the stage when amyloid protein was not detected in mice(2 months of age).Mice in the xueshuantong group(APP/PS1+PNS)were administered by gavage once a day at a dose of 60 mg/kg for six months(for 8 months of age).The mice of the control group were given 0.9%sodium chloride(APP/PS1+Vehicle)intragastric treatment of the same volume,while the wild-type mice of the same age were given 0.9%sodium chloride intragastric treatment as the normal control group(WT+Vehicle)(15 mice in each group,n=15).After six months,the cognitive function of the mice was evaluated by the Novel Object Recognition(NOR)task and Morris Water Maze(MWM)test.The activity of BACE1,the distribution and expression of Nav1.1α,as well as the expression and enzymatic hydrolysis of Navβ2(Navβ2 full-length and Navβ2-CTF fragments)in cortex and hippocampus were detected by EEG,Western blot and cell surface biotinylation assay,respectively.Results The NOR task showed that compared with the mice in the APP/PS1+Vehicle group,the Discrimination index(DI)of mice in the APP/PS1 group was significantly increased after xueshuantong administration(P<0.05).The MWM test found that,the escape latency of the mice in the xueshuantong group was shortened followed six months in gastric administration(P<0.05),while the stay time in the target quadrant and the number of platforms significantly increased(P<0.05)after the removal of the platform.The results of EEG recording showed that xueshuantong reduced the frequency of spike-wave discharges in APP/PS1 mice(P<0.05).Furthermore,xueshuantong significantly reduced the expression of BACE1(P<0.05).In the APP+PNS group,the expression of Navβ2 full-length was increased(P<0.05),as well as corrected the abnormal distribution of Nav1.1α inside and outside of neurons(P<0.05).Conclusion Treatment with xueshuantong can significantly improve the learning and memory ability and correct the abnormal excitability of the brain in AD model mice.The mechanism may be related to the inhibition of BACE1 activity,the reduction of APP/PS1-induced excessive enzyme digestion of Navβ2,the correction of the abnormal expression and distribution of Nav1.1α in cortical and hippocampal neurons,as well as the subsequent regulation of neuronal excitability.

Objective:To examine the associations of pre-pregnancy body mass index (BMI), gestational weight gain, and gestational diabetes mellitus (GDM) with early childhood BMI trajectories.Methods:A total of 1 227 mother-child pairs from the Peking University Birth Cohort in Tongzhou were included in this study. In the cohort, maternal pre-pregnancy weight, height, gestational weight gain, and GDM diagnosis were collected. The children were followed up at birth and at 1, 3, 6, 9, 12, 18, 24, 30, and 36 months of age to obtain height/length and weight data. The longitudinal data-based k-means clustering algorithm was used to identify early childhood BMI trajectory groups. The associations of maternal pre-pregnancy BMI, gestational weight gain, and GDM with early childhood BMI trajectories were analyzed using the logistic regression model. We further explored whether there is an interaction effect between pre-pregnancy overweight/obesity and excessive gestational weight gain on the risk of the high BMI trajectory in early childhood through multiplicative and additive interaction analyses. Results:The prevalence rates of overweight and obesity before pregnancy were 21.2% (260 cases) and 6.6% (81 cases) respectively. The prevalence of excessive gestational weight gain and GDM was 57.7% (708 cases) and 30.9% (379 cases). The early childhood BMI trajectories were named low, medium, and high trajectories, accounting for 30.5%, 45.4% and 24.1%, respectively. After controlling potential confounding factors, it was found that pre-pregnancy overweight ( OR=1.54, 95% CI: 1.12-2.12), obesity ( OR=2.33, 95% CI: 1.41-3.85), and excessive gestational weight gain ( OR=1.47, 95% CI: 1.10-1.97) were risk factors for being in the high BMI trajectory in early childhood. GDM was not significantly associated with early childhood BMI trajectories ( P>0.05). Compared with the independent effects of pre-pregnancy overweight/obesity ( OR=1.90, 95% CI: 1.17-3.09) and excessive gestational weight gain ( OR=1.45, 95% CI: 1.03-2.04), the risk of being in the high BMI trajectory in early childhood was greater when the two factors coexisted ( OR=2.38, 95% CI: 1.60-3.54). However, both the multiplicative and additive models showed no interaction effect between pre-pregnancy overweight/obesity and excessive gestational weight gain. Conclusions:Maternal pre-pregnancy overweight/obesity and excessive gestational weight gain are independent risk factors for children being in the high BMI trajectory in early childhood, providing scientific evidence for obesity prevention.

Thyroid diseases are common endocrine disorders with high incidence. The diseases are closely related to genetic factors， immune system disorders， and hormone levels. Although modern medical therapies have achieved certain therapeutic effects， the side effects have affected clinical treatment. In recent years， studies have proven that gut microbiota is a key factor affecting thyroid diseases， and increasing studies have referred to the bidirectional information interaction system between the gut and thyroid as the gut-thyroid axis. This study adopts the meridian-collateral theory and the visceral manifestation theory of traditional Chinese medicine （TCM） to explain the functions， physiological characteristics， and pathological mechanisms of the gut and thyroid. Furthermore， this paper clarifies the mechanism of gut microbiota in modulating thyroid homeostasis by inducing inflammation and altering thyroid hormone metabolism from the perspective of molecular biology， clarifying the rationality of the gut-thyroid axis from the perspectives of TCM and Western medicine. Meanwhile， under the guidance of the gut-thyroid axis， increasing studies have been carried out regarding the application of TCM in regulating gut microbiota in the treatment of thyroid diseases. Both the active component emodin and compound prescription Yiqi Huatan Huoxue prescription of Chinese medicine can treat thyroid diseases by regulating the abundance and diversity of gut microbiota and improving the intestinal mucosal barrier. However， the systematic review of the research on TCM treatment of thyroid diseases by regulating gut microbiota remains to be conducted. This study expounds the gut-thyroid axis from both TCM and Western medicine and reviews the research progress in the TCM treatment of thyroid diseases by regulating gut microbiota， aiming to give new insights into the prevention and treatment of thyroid diseases with TCM.

Objective:To investigate the predictive value of myocardial perfusion-related parameters measured by echocardiography on the prognosis of patients with coronary artery disease at 90 d after percutaneous coronary intervention (PCI).Methods:Eighty-five patients with coronary artery disease who underwent PCI in Linping Branch of the Second Affiliated Hospital of Zhejiang University from October 2020 to October 2022 were selected retrospectively. Patients were divided into the occurrence myocardial perfusion injury group (40 cases) and the non-occurrence myocardial perfusion injury group (45 cases). The quantitative echocardiographic parameters of left ventricular end-diastolic internal diameter (LVEDD) and left ventricular end-systolic internal diameter (LVESD) were compared between the two groups, and the effects of LVEDD and LVESD on the risk of myocardial perfusion injury after PCI in patients with coronary artery disease were analyzed. Logistic regression was used to analyze the factors influencing the major adverse cardiovascular events (MACE) of patients with coronary artery disease at 90 d after PCI. A line graph model was constructed, the receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were constructed to verify the predictive efficiency of the line graph model.Results:Compared with the day of admission, the levels of LVEDD and LVESD were increased at 2 and 6 h after PCI, and showed an increasing trend at each time point ( P<0.05). The levels of LVEDD and LVESD at 2 and 6 h after PCI in the occurrence myocardial perfusion injury group were higher than those in the non-occurrence myocardial perfusion injury group: (45.56 ± 2.35) mm vs. (43.27 ± 2.12 ) mm, (47.87 ± 3.56) mm vs. (45.73 ± 2.98) mm; (33.49 ± 2.32) mm vs. (31.29 ± 2.29) mm, (35.62 ± 3.03) mm vs. (33.74 ± 2.12) mm, there were statistical differences ( P<0.05). The risk of myocardial perfusion injury was 4.469 and 6.081 times higher in patients with high levels of LVEDD and LVESD than in patients with low levels. The results of Logistic regression analysis showed that coronary multiple lesions, time from onset to balloon dilation, coronary Gensini score and LVEDD, LVESD were independent influencing factors of MACE at 90 d after PCI in patients with coronary artery disease ( P<0.05). Based on the above five independent influencing factors, a column line graph model was established to predict the risk of poor prognosis at 90 d after PCI. According to the column line graph model, the coronary multiple lesions were scored as 5; the corresponding prognostic adverse risk increased with the increase of time from onset to balloon dilation, coronary Gensini score and quantitative echocardiographic parameters LVEDD and LVESD; the internal validation of the column line graph prediction model was performed, and the C-index of the model was 0.978; the calibration curve showed that the model had good differentiation and accuracy in predicting the risk of MACE at 90 d after PCI. The results of ROC curve showed, the area under the curve (AUC) was 0.955 (95% CI 0.952 - 1.000). The DCA showed that when the line graph model was in the high risk threshold range (0 - 0.9), the prediction of the model had clinical practical value and the net benefit of patients was high. Conclusions:The abnormal increase of LVEDD and LVESD determined by echocardiography is associated with myocardial perfusion injury in patients with coronary heart disease after PCI, and a line graph model based on LVEDD and LVESD can predict the occurrence of MACE at 90 d after PCI, so as to guide early risk assessment and prevention.

Breastfeeding difficulties are common among malnourished infants,and exclusive breastfeed-ing is one of the most effective means of ameliorating their malnutrition.Effective assessment is the first step for realizing exclusive breastfeeding.At present,there is a lack of assessment tools aiming at specific breast-feeding.This paper summarized the breastfeeding assessment tools applicable in this field,and introclued the content and role of breastfeeding assessment tools in order to further perfect the breastfeeding assessment tools to help the malnourished infants to achieve exclusive breastfeeding and promote their growth and development.

Objective To investigate the clinical efficacy and safety of endoscopic resection using snares for the treatment of gastric submucosal tumors(SMTs).Methods 66 patients diagnosed with gastric SMTs and treated with endoscopic resection from August 2017 to August 2023 were retrospectively analyzed and divided into the snare group(endoscopic resection using snares,n=33)and the traditional resection group(endoscopic resection using a traditional disposable incision knife,n=33).The operation time,overall resection rate,incidence of adverse reactions,operation cost,hospitalisation cost,and the post-operative hospital days were compared between the two groups.Results The lesion diameter was 8.00(6.00,14.00)mm in the snare group and 8.00(7.50,10.00)mm in the traditional resection group,the difference between the two groups was not statistically significant(P>0.05);The operative time in the snare group was significantly shorter than that in the traditional resection group[26.00(19.00,30.50)min vs 33.00(22.50,49.50)min],the difference was statistically significant(P<0.05);The overall resection rate in both groups was 100.0%;Neither group of patients had intraoperative perforation.There were no statistically significant differences in the incidence of adverse reactions such as intraoperative bleeding,abdominal pain and fever between the two group(P>0.05);The operative cost of the snare group was significantly lower than the traditional endoscopic resection group[(8 642.18±1 078.56)yuan vs(13 266.45±2 160.80)yuan],the difference was statistically significant(P<0.05).Conclusion Compared with traditional surgical instruments,endoscopic resection of gastric SMTs using snares has a shorter operating time,lower surgical costs,safe and effective,making it worthy of promotion.