ObjectiveTo evaluate the efficacy of Shexiang Baoxinwan in treating stable angina pectoris with Qi stagnation and blood stasis syndrome in patients with coronary artery disease （CAD） complicated with anxiety and depression and explore its underlying mechanisms. MethodsThis study employed a randomized， double-blind， and placebo-controlled clinical trial design. Patients admitted to the hospital were randomly assigned to the observation group and the control group， with 52 patients in each group. Patients in the observation and control groups received Shexiang Baoxinwan and placebo， respectively， both in combination with conventional Western medication. The dose was 45.0 mg， three times daily， for a total duration of eight weeks. The primary outcome was the Seattle Angina Questionnaire （SAQ） scores before and after treatment. Secondary outcomes included changes in traditional Chinese medicine （TCM） syndrome score， the patient health questionnaire-9 （PHQ-9）， generalized anxiety disorder-7 （GAD-7）， inflammatory markers ［interleukin-18 （IL-18）， interleukin-10 （IL-10）， tumor necrosis factor-alpha （TNF-α）， CD40， etc.］， monoamine neurotransmitters ［e.g.， dopamine （DA）］， vascular endothelial function markers ［e.g.， endothelin-1（ET-1）］， adipokines， and ischemia-modified albumin （IMA）. Adverse reactions were also recorded. ResultsA total of 92 patients completed the study， with 44 in the observation group and 48 in the control group. Compared with baseline， both groups showed significant decreases in PHQ-9， GAD-7， and TCM syndrome scores following treatment （P<0.05）， along with a significant increase in SAQ scores （P<0.05）. In the observation group， DA levels were significantly increased （P<0.05）， while levels of IL-18， TNF-α， CD40， ET-1， and IMA were decreased （P<0.05）. In contrast， the control group exhibited significantly increased CD40 levels （P<0.05）. Compared with the control group after treatment， the observation group showed significant improvements in the SAQ dimensions of physical limitation， angina stability， treatment satisfaction， and disease perception， as well as in TCM syndrome score， PHQ-9 score， IL-18， CD40， ET-1， and IMA （P<0.05）. No adverse reactions were observed in either group during treatment. ConclusionShexiang Baoxinwan can improve anxiety and depression， alleviate angina symptoms， and reduce TCM symptoms of Qi stagnation and blood stasis in CAD patients. The mechanism may involve anti-inflammation， improvement of vascular endothelial function， reduction of IMA， and increase of monoamine neurotransmitter levels.

ObjectiveTo evaluate the efficacy of Shexiang Baoxinwan in treating stable angina pectoris with Qi stagnation and blood stasis syndrome in patients with coronary artery disease （CAD） complicated with anxiety and depression and explore its underlying mechanisms. MethodsThis study employed a randomized， double-blind， and placebo-controlled clinical trial design. Patients admitted to the hospital were randomly assigned to the observation group and the control group， with 52 patients in each group. Patients in the observation and control groups received Shexiang Baoxinwan and placebo， respectively， both in combination with conventional Western medication. The dose was 45.0 mg， three times daily， for a total duration of eight weeks. The primary outcome was the Seattle Angina Questionnaire （SAQ） scores before and after treatment. Secondary outcomes included changes in traditional Chinese medicine （TCM） syndrome score， the patient health questionnaire-9 （PHQ-9）， generalized anxiety disorder-7 （GAD-7）， inflammatory markers ［interleukin-18 （IL-18）， interleukin-10 （IL-10）， tumor necrosis factor-alpha （TNF-α）， CD40， etc.］， monoamine neurotransmitters ［e.g.， dopamine （DA）］， vascular endothelial function markers ［e.g.， endothelin-1（ET-1）］， adipokines， and ischemia-modified albumin （IMA）. Adverse reactions were also recorded. ResultsA total of 92 patients completed the study， with 44 in the observation group and 48 in the control group. Compared with baseline， both groups showed significant decreases in PHQ-9， GAD-7， and TCM syndrome scores following treatment （P<0.05）， along with a significant increase in SAQ scores （P<0.05）. In the observation group， DA levels were significantly increased （P<0.05）， while levels of IL-18， TNF-α， CD40， ET-1， and IMA were decreased （P<0.05）. In contrast， the control group exhibited significantly increased CD40 levels （P<0.05）. Compared with the control group after treatment， the observation group showed significant improvements in the SAQ dimensions of physical limitation， angina stability， treatment satisfaction， and disease perception， as well as in TCM syndrome score， PHQ-9 score， IL-18， CD40， ET-1， and IMA （P<0.05）. No adverse reactions were observed in either group during treatment. ConclusionShexiang Baoxinwan can improve anxiety and depression， alleviate angina symptoms， and reduce TCM symptoms of Qi stagnation and blood stasis in CAD patients. The mechanism may involve anti-inflammation， improvement of vascular endothelial function， reduction of IMA， and increase of monoamine neurotransmitter levels.

ObjectiveTo investigate the chemosensitization effect of gallic acid （GA） combined with sorafenib （Sora） on hepatocellular carcinoma HepG2 cells and related mechanisms. MethodsHepG2 cells were randomly divided into control group， GA group， Sora group， and GA+Sora group. CCK8 assay was used to measure cell viability； CompuSyn software was used to analyze combination index （CI）； colony formation assay was used to evaluate the colony formation ability of cells； flow cytometry was used to measure cell apoptosis； wound healing assay and Transwell chamber assay were used to observe the migration and invasion abilities of cells； Western Blot was used to measure the expression matrix metalloproteinase 2 （MMP-2）， matrix metalloproteinase 9 （MMP-9）， and apoptosis-related proteins. HepG2 cells were subcutaneously inoculated into the lower right back of mice， and 6 days later， the mice were divided into control group， GA group， Sora group， and GA+Sora group. Tumor size and body weight were measured once a week， and drug intervention was performed for 21 days. Then the nude mice were sacrificed， and tumor weight was measured. A one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsThe mean IC₅₀ values of GA and Sora for the treatment of HepG2 cells for 48 hours were 123.47±5.16 μmol/L and 9.87±0.98 μmol/L， respectively， and when Sora was combined with 70 μmol/L GA （IC₃₀）， IC₅₀ decreased to 2.06±0.35 μmol/L； the CI value was<1 for Sora at different concentrations combined with 70 μmol/L GA. The number of cell colonies was 234.0±20.4， 147.0±12.1， 129.3±13.3， and 73.0±7.6， respectively， in the four groups， and the GA+Sora group had a significantly lower number of cell colonies than the control group， the GA group， and the Sora group （all P<0.05）. After 48 hours of treatment， the cell apoptosis rate was 1.98%±0.29%， 15.17%± 1.56%， 18.65%±1.48%， and 34.60%±5.36%， respectively， in the four groups， and the GA+Sora group had a significantly higher cell apoptosis rate than the control group， the GA group， and the Sora group （all P<0.05）. After 24 hours of treatment， the cell migration rate was 55.59%±5.08%， 29.34%±4.36%， 21.80%±5.16%， and 6.47%±2.75%， respectively， in the four groups， and the GA+Sora group had a significantly lower cell migration rate than the control group， the GA group， and the Sora group （all P<0.05）. After 48 hours of treatment， the number of transmembrane cells was 223.7±13.0， 168.3±10.9， 155.3±29.1， and 62.7±19.7， respectively， in the four groups， and the GA+Sora group had a significantly lower number of transmembrane cells than the control group， the GA group， and the Sora group （all P<0.05）. Compared with the control group， the GA group， the Sora group， and the GA+Sora group had significant reductions in the protein expression levels of MMP-2， MMP-9， and Bcl-2 （all P<0.05） and significant increases in the protein expression levels of Bax and cleaved caspase-3 （all P<0.05）. Compared with the control group， the GA， Sora， and GA+Sora groups had significant reductions in tumor volume and weight （all P<0.05）， and compared with the Sora group， the GA+Sora group had significant reductions in tumor volume and weight in nude mice （both P<0.05）. ConclusionGA can increase the sensitivity of HepG2 cells to Sora chemotherapy， possibly by promoting cell apoptosis and inhibiting cell migration and invasion after combination with Sora.

ObjectiveTo investigate the effect of gallic acid （GA） on the proliferation， migration， invasion， and apoptosis of human hepatocellular carcinoma HepG2 cells and its mechanism. MethodsHepG2 cells were treated with different concentrations of GA （0， 5， 10， 20， 30， 40， and 50 μg/mL） for 24 and 48 hours， and CCK8 assay was used to measure cell viability and calculate IC₅₀. The experiment was divided into control group （HepG2 cells）， 5 μg/mL GA group， 10 μg/mL GA group， and 20 μg/mL GA group. Plate colony formation assay was used to evaluate the effect of GA on cell proliferation； wound healing assay and Transwell chamber assay were used to observe the effect of GA on cell migration and invasion； flow cytometry was used to observe the effect of GA on cell apoptosis； Western blot was used to measure the expression of matrix metallopeptidase-2 （MMP-2）， matrix metallopeptidase-9 （MMP-9）， and apoptosis-related proteins. A one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsThe mean IC₅₀ value of GA on HepG2 cells was 38.02±2.58 μg/mL at 24 hours and 18.36±1.54 μg/mL at 48 hours. The number of cell colonies was 239.00±29.45 in the control group， 210.00±19.00 in the 5 μg/mL GA group， 144.33±16.03 in the 10 μg/mL GA group， and 57.00±9.55 in the 20 μg/mL GA group， suggesting that compared with the control group， each GA group had a significant reduction in cell colony formation ability （all P<0.05）. After 24 hours of treatment， the cell migration rate was 42.62%± 7.82% in the control group， 35.34%±6.42% in the 5 μg/mL GA group， 21.85%±4.42% in the 10 μg/mL GA group， and 12.57%± 3.54% in the 20 μg/mL GA group， respectively， in these four groups， and the number of transmembrane cells in these four groups was 230.30±15.30， 182.12±12.60， 137.20±7.50， and 124.40±6.80， respectively， suggesting that compared with the control group， each GA group had significant reductions in migration rate and the number of transmembrane cells （all P<0.05）. After 48 hours of treatment， the cell apoptotic rate was 0.67%±0.08% in the control group， 13.27%±1.07% in the 5 μg/mL GA group， 20.94%± 2.45% in the 10 μg/mL GA group， and 40.74%±2.63% in the 20 μg/mL GA group， and compared with the control group， each GA group had a significant increase in cell apoptosis rate （all P<0.05）. Compared with the control group， each GA group had significant reductions in the protein expression levels of MMP-2 and MMP-9 （all P<0.05） and significant increases in the protein expression levels of Bax and cleaved caspase-3 （all P<0.05）. ConclusionGA can inhibit the proliferation， migration， and invasion of HepG2 cells and promote the apoptosis of HepG2 cells， possibly by regulating MMP-2， MMP-9， and the apoptosis-related proteins Bax/Bcl-2.

Objective To understand the status of intra-abdominal hypertension(IAH)in children after liver transplantation,and to analyze the risk factors,to provide references for clinical medical staff to identify high-risk early,and formulate the prevention and intervention program of IAH after liver transplantation.Methods A prospective cohort study was conducted,and the clinical data of 208 children who received liver transplantation from October 2021 to June 2023 in a tertiary hospital in Zhejiang Province were enrolled.The status of IAH after liver transplantation was described,and participants were divided into 2 groups according to transbladder monitoring intra-abdominal pressure levels.Children with ≥10 mmHg(1 mmHg=0.133 kPa)was classified as an intra-abdominal hypertension group,while those with＜10 mmHg was classified as a non-intra-abdominal hypertension group.Results There were 51 cases(24.52％)which had IAH,including 12 cases(23.53％)of grade I to Ⅱ and 39 cases(76.47％)of grade Ⅲ to Ⅳ in 208 intra-abdominal hypertension in children after liver transplantation.Binary Logistic regression analysis showed that the graft to recipient weight ratio(OR=1.391),duration of postoperative mechanical ventilation(OR=1.006),and postoperative central venous pressure(OR=1.375)were independent risk factors for IAH(P＜0.05).Conclusion The incidence of IAH in children after liver transplantation were high.Greater graft to recipient weight ratio,longer mechanical ventilation time,higher central venous pressure could increase the risk of IAH.During clinical practice,more emphasis should be strengthened on the abdominal pressure dynamic monitoring and providing timely intervention to reduce the occurrence of IAH,and improving the prognosis of children after liver transplantation.

Objective In this research,we constructed a nurse-led intra-abdominal pressure(IAP)management program in children undergoing liver transplantation,and explored its clinical application effect.Methods Based on literature review,semi-structured interviews,and expert meetings,a nurse-led program for IAP management is constructed.By convenience sampling method,162 children admitted to the pediatric liver transplant intensive care unit of a tertiary hospital in Zhejiang Province from January to December 2023 were selected.The experimental group implemented a nurse-led IAP management program,while the control group received routine postoperative care after liver transplantation.The average IAP values during ICU period,incidence and grading of intra-abdominal hypertension(IAH),duration of mechanical ventilation,and length of ICU stay were compared between 2 groups.Results Finally,the IAP management program in children undergoing liver transplantation included 4 first-level items,10 second-level items and 20 third-level items.During the application of this program,4 cases dropped,and 78 cases were finally included in the experimental group and 80 cases in the control group.After the intervention,the IAP value in the experimental group was(8.63±2.40)mmHg(1 mmHg=0.133 kPa),lower than(9.23±3.19)mmHg in the control group,but there was no statistically significant difference between the 2 groups(P=0.186).The incidence of IAH in the experimental group was 23.07％,lower than 41.25％in the control group.The difference between the 2 groups was statistically significant(P=0.015).13 cases(16.67％)in the experimental group developed grade Ⅰ IAH,while 22 cases(27.50％)in the control group;5 cases(6.41％)in the experimental group developed grade Ⅱ IAH,while 9 cases(11.25％)in the control group;no cases in the experimental group developed grade Ⅲ IAH,while 2 cases(2.50％)in the control group.There was no statistically significant difference between the 2 groups(P＞0.05).The mechanical ventilation time in the experimental group was 3.00(1.00,13.25)hours,and 7.50(1.00,27.75)hours in the control group.The difference between the 2 groups was statistically significant(P=0.034).The length of ICU stay in the experimental group was 6.00(4.00,8.25)days,and 5.00(3.00,8.00)days hours in the control group.The difference between the 2 groups was statistically significant(P=0.061).Conclusion The nurse-led IAP management program in children undergoing liver transplantation can effectively reduce the incidence of IAH,shorten the duration of mechanical ventilation.

Background Multimorbidity imposes a heavy burden on individuals, families, and society. There are relatively few studies exploring patterns of multimorbidity among middle-aged adults in China. Objective To explore the current status of multimorbidity, associated risk factors, and multimorbidity patterns among adults aged 45-64 years in China, so as to provide a scientific basis to prevent and control multimorbidity in China. Methods A total of 5494 adults aged 45-64 years from the Chinese Health and Nutrition Survey (CHNS) in 2018 were selected. Of these, 2494 (45.39%) were men and 3000 (54.61%) were women. The nine diseases included were hypertension, diabetes, dyslipidaemia, obesity, mild cognitive impairment (MCI), myocardial infarction, stroke, asthma, and tumor. The prevalence of each disease or multimorbidity was expressed as N (%). Comparisons of multimorbidity prevalence between different groups were performed using the χ² test or Cochran-Armitage trend test. Association rule with the Apriori algorithm was used to explore the pattern of multimorbidity, with parameters set at a minimum conditional support of 3.00%, a minimum rule confidence of 50.00%, and a lift of >1.20. Logistic regression was used to evaluate the associations between selected risk factors and multimorbidity. Results In 2018, 37.44% of participants reported multimorbidity in 15 provinces of China. The prevalence of diseases in descending order was dyslipidaemia (39.99%), hypertension (39.48%), obesity (16.42%), MCI (14.47%), diabetes (14.16%), tumor (1.09%), stroke (1.04%), myocardial infarction (0.71%), and asthma (0.64%). A total of seven multimorbidity patterns were identified in this group. Obesity paired with hypertension, and diabetes paired with dyslipidemia were the two major patterns of multimorbidity in the general population and age or sex subgroups. The multimorbidity patterns of different populations were concentrated in the combination of obesity, hypertension, diabetes, and dyslipidemia. The risk of multimorbidity was lower in females than in males (OR=0.85, 95%CI: 0.75, 0.97). The multimorbidity risk was 1.56 times higher in the 55-64 years group than in the 45-54 years group (OR=1.56, 95%CI: 1.40, 1.75). Drinking in the past year increased the risk of multimorbidity by 25% (OR=1.25, 95%CI: 1.08, 1.45) compared to no alcohol comsumption in the past year. High and medium levels of physical activity were associated with a decreased OR (high: OR=0.74, 95%CI: 0.65, 0.85; medium: OR=0.81, 95%CI: 0.70, 0.93) with low level of physical activity as reference. Conclusion In 2018, there was a high prevalence rate of multimorbidity among middle-aged adults in China. The main multimorbidity patterns were obesity-hypertension and diabetes-dyslipidemia. Surveillance and interventions should be strengthened particularly for men, individuals with alcohol consumption or insufficient physical activity, and those with major multimorbidity patterns.

Objective To establish a method and study the pharmacokinetics for concentration determination of effective components in Xiakucao Xiaoliu mixture in Normal Rat Plasma By LC-MS/MS. Methods The mobile phase was methanol-water (0.1% formic acid) system under the positive ion mode of C18 chromatographic column, gradient elution was adopted, and the flow rate was 0.3 ml/min. In the negative ion mode, the mobile phase was acetonitrile-water (0.1% formic acid) system, gradient elution, with a flow rate of 0.4 ml/min. Caffeic acid, rosmarinic acid, syringic acid, rutin in positive ion mode and Atractylodes lactone II and Atractylodes lactone III in negative ion mode were respectively determined. Normal rats were intragastrically given Xiakucao Xiaoliu Mixture 7.8 ml/kg, and blood was taken from the orbit at different time points after the administration. The blood concentration was determined by the validated LC-MS/MS method and the non-standard DAS2.0 software was used. The pharmacokinetic parameters of rats after administration were calculated by the compartment model. Results The pharmacokinetic parameters belonged to non atrioventricular model. The pharmacokinetic characteristics of the four main anti-cancer active ingredients of Caffeic acid, Rosmarinic acid, Syringic acid and Atractylodes Ⅲ in rats after administration of Xiakucao Xiaoliu Mixture were significantly different from those reported in the literature after the administration of monomers. Conclusion The established method was simple, accurate and sensitive, which could be suitable for the content determination of effective components in Xiakucao Xiaoliu mixture in Normal Rat Plasma, which would be a valuable information for the study on main anticancer active substances.

Background Diabetes is a major contributor to global burden of disease. The role of magnesium in the prevention of diabetes has aroused concern. However, the research results on the impact of dietary magnesium on the risk of diabetes are hitherto inconsistent. Objective To evaluate the association between dietary magnesium intake and the risk of diabetes through a systematic review. Methods PubMed, Web of Science, China National Knowledge Infrastructure, Wanfang databases were searched for prospective studies that contained risk estimates for magnesium intake-associated diabetes and were published from January 1, 2000 to December 31, 2021. Two researchers independently screened the literature according to a set of pre-prepared inclusion and exclusion criteria, extracted the data according to an unified data extraction table, and evaluated the quality of included articles with Newcastle-Ottawa Scale (NOS). R 4.0.3 software and Stata SE16.0 software were used for meta-analysis and subgroup meta-analysis, and Higgins I² statistics were used to test the heterogeneity of the included studies. The sources of heterogeneity were analyzed by univariate meta regression. Results A total of 14 articles involving 17 prospective cohort studies (1065267 participants and 40506 patients with diabetes) were included in the study. The NOS scores ranged from 8 to 9, with an average of 8.6, indicating that the included studies were classified as being high quality. The highest quintile of magnesium intake group reduced the risk of diabetes by 22% (RR=0.78, 95%CI: 0.73-0.82) compared with the lowest quintile group. This association was not substantially modified by geographic region, sex, or follow-up length. The highest quintile of dietary magnesium intake in the Americas and Asia were associated with 22% and 26% reductions in the risk of type 2 diabetes respectively compared with the lowest quintile group (the Americas, RR=0.78, 95%CI: 0.73-0.84; Asia, RR=0.74, 95%CI: 0.63-0.88); The highest quintile of dietary magnesium intake in female, male and without gender stratified were associated with 22%, 19% and 46% reductions in the risk of type 2 diabetes respectively compared with the lowest quintile group (Female RR=0.78, 95%CI: 0.73-0.84; Male RR=0.81, 95%CI: 0.74-0.89; Both RR=0.54, 95%CI: 0.42-0.68); Compared with the lowest quintile groups, the groups with the highest quintile of dietary magnesium intake with a follow-up time of less than 10 years and more than 10 years reduced the risk of type 2 diabetes by 26% and 20% respectively (≤10 years, RR=0.74, 95%CI: 0.65-0.83; ＞10 years, RR=0.80, 95%CI: 0.75-0.85). After adjusting for hypertension, the highest quintile of dietary magnesium intake group reduced the risk of type 2 diabetes by 20% compared with the lowest quintile group (RR=0.80, 95%CI: 0.74-0.85). The year of publication (P<0.05) or the sex of the subjects (P<0.05) may be the source of heterogeneity by meta regression test. The results of Egger’s test for funnel plot asymmetry suggested publication bias. Conclusion The combined data supports a role for high magnesium intake in reducing the risk of type 2 diabetes. Because it is difficult to separate the effect of magnesium intake on diabetes risk from other factors, large-scale and clinical randomized controlled trials are needed to directly assess the impact of magnesium on the incidence rate of diabetes.

Crossmodal information processing in sensory cortices has been reported in sparsely distributed neurons under normal conditions and can undergo experience- or activity-induced plasticity. Given the potential role in brain function as indicated by previous reports, crossmodal connectivity in the sensory cortex needs to be further explored. Using perforated whole-cell recording in anesthetized adult rats, we found that almost all neurons recorded in the primary somatosensory, auditory, and visual cortices exhibited significant membrane-potential responses to crossmodal stimulation, as recorded when brain activity states were pharmacologically down-regulated in light anesthesia. These crossmodal cortical responses were excitatory and subthreshold, and further seemed to be relayed primarily by the sensory thalamus, but not the sensory cortex, of the stimulated modality. Our experiments indicate a sensory cortical presence of widespread excitatory crossmodal inputs, which might play roles in brain functions involving crossmodal information processing or plasticity.
Animals ; Auditory Cortex/physiology* ; Neuronal Plasticity/physiology* ; Neurons ; Rats ; Thalamus ; Visual Cortex/physiology*