Tracheobronchial adenoid cystic carcinoma （TACC） is a low-grade malignant tumor originating from the airway mucosa. Despite its slow progression，it is characterized by high invasiveness，frequent recurrence，and a strong tendency for metastasis. Preclinical studies have shown that vascular-targeted therapy holds significant potential. However，an effective systemic treatment for TACC has not been established yet. This study explored TACC from the perspective of "Feiji" in traditional Chinese medicine （TCM） as the starting point. It deeply investigated the mechanisms of abnormal collaterals and tumor vascular recruitment and further elaborated on the theoretical connection between abnormal collaterals and tumor vascular recruitment. Firstly，collateral hyperactivity led to disordered and erratic pulmonary collaterals. Their abnormal structures were similar to the disorderly and tortuous nature of tumor （pseudo）angiogenesis. This resulted in imbalances in the functions of circulation，perfusion，and reverse injection of the pulmonary collaterals，and then led to unrestrained collateral dysfunction and the accumulation of pathogenic factors. Secondly，the remodeling of the extracellular matrix （ECM） and epithelial-mesenchymal transition （EMT） in TACC were critical processes in vascular co-option （VCO），representing the micro-level manifestation of the displacement of nutrient and defense. During this process，ECM remodeling made TACC cells more likely to hijack normal blood vessels，creating a complex vascular microenvironment conducive to tumor growth. In terms of treatment，this study proposed a TCM strategy of "regulating collaterals to expel pathogenic factors and nourishing collaterals to strengthen the healthy Qi"，and listed potential TCM. These were intended to regulate the Qi and blood in the collaterals，repair the functions of abnormal collaterals，and intervene in the vascular recruitment process of TACC. Future research should focus on improving the TCM clinical syndrome characteristics of TACC. Through modern molecular biology techniques，it is necessary to deeply analyze the micro-level pattern of vascular recruitment in TACC. This would enrich the understanding of the profound connection between abnormal collaterals and tumor vascular recruitment，providing empirical evidence for TCM-targeted therapies for vascular recruitment in TACC.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Objective To observe the clinical efficacy and safety of nivolumab combined with anlotinib in the treatment of patients with advanced gastric cancer.Methods The patients with advanced gastric cancer were randomly divided into control group and treatment group.The control group received oral apatinib capsules 12 mg,once a day,and discontinued treatment for 7 days after 14 days of maintenance therapy.On the basis of control group,the treatment group received intravenous infusion of 3 mg·kg-1 nivolumab,once every two weeks.Two groups were treated for four cycles with 21 days per cycle.The clinical efficacy,tissue polypeptide specific antigen(TPS),carbohydrate antigen 125(CA125),carcinoembryonic antigen(CEA)and adverse drug reactions were compared between two groups.Results In the treatment group,80 cases were enrolled,and 4 cases dropped out and 76 cases were included in the statistical analysis;in the control group,80 cases were enrolled,and 8 cases dropped out and 72 cases were included in the statistical analysis.After treatment,the total effective rates in the treatment and control group weres 78.95％(60 cases/76 cases)and 52.78％(38 cases/72 cases),and the difference was statistically significant(P＜0.05).After treatment,the levels of CEA in the treatment and control groups were(5.34±1.12)and(7.01±0.97)U·mL-1;the levels of CA125 were(22.65±4.27)and(27.61±5.09)U·mL-1;the levels of TPS were(69.21±11.64)and(53.06±10.57)U·mL-1;these differences were statistically significant(all P＜0.05).The adverse drug reactions of two groups were nausea/diarrhea,leukopenia,thrombocytopenia,abnormal liver function,and hypothyroidism.The total incidences of adverse drug reactions in the treatment and control groups were 40.79％and 37.50％without statistically significant difference(P＞0.05).Conclusion Ramucirumab injection combined with anlotinib capsules is more effective than single-agent anlotinib in the treatment of advanced gastric cancer,without increasing the incidence of adverse drug reactions.

AIM To investigate the effects of Zhuangyao Shuanglu Tongnao Formula on neuronal apoptosis in rats with cerebral ischemia-reperfusion injury based on the study of oxidative stress and inflammatory response.METHODS The rats were randomly divided into the sham operation group,the model group,the edaravone group(3.0 mg/kg),the low,medium and high dose groups(9.0,18.0,36.0 g/kg)of Zhuangyao Shuanglu Tongnao Formula,with 18 rats in each group.The middle cerebral artery occlusion/reperfusion was conducted by thread embolism method to simulate cerebral ischemia reperfusion injury in rats followed by 6 days corresponding drugs administration.Subsequently,the rats had their neurological function deficit scored by Zeal Longa scoring method;their sizes of cerebral infarction areas measured by TTC staining;their pathological damage and apoptosis of neurons in hippocampal CA1 area of ischemic penumbra of the brain tissue detected by HE staining and TUNEL staining;their SOD activity and levels of GSH,MDA,IL-6,IL-1β,TNF-α in brain tissue detected by kits;and their protein expressions of Bax,Bcl-2,caspase-3,cleaved-capase-3,TLR4,NF-κB p65,Nrf2,HO-1 in rat brain tissue determined by Western blot.RESULTS Compared with the model group,the groups intervened with edaravone,medium and high dose of Zhuangyao Shuanglu Tongnao Formula displayed improvements in the scores of nerve function defects,the rate of cerebral infarction,the rate of neuronal apoptosis,the levels of IL-6,IL-1β,TNF-α and MDA in the ischemic penumbra of brain tissues,the protein expressions of Bax and TLR4,the ratio of cleaved-capase-3/caspase-3 and p-NF-κB p65/NF-κB p65(P＜0.05),the levels of GSH,the activity of SOD and the protein expressions of Bcl-2,Nrf2 and HO-1(P＜0.05).CONCLUSION Being an inhibitor of oxidative stress and inflammatory response,Zhuangyao Shuanglu Tongnao Formula can alleviate brain injury in rats with cerebral ischemia reperfusion injury through the inhibition of neuronal apoptosis and improvement of neural function mediated by the inhibition of TLR4/NF-κB signal pathway and activation of Nrf2/HO-1 signal pathway.

Objective To investigate the effects of Erhuang Quzhi Granules combined with Silibinin Capsules on fatty liver index,inflammatory factors and autophagy-related gene levels in patients with nonalcoholic fatty liver disease(NAFLD).Methods A total of 126 patients with NAFLD of phlegm blended with blood stasis type were randomly divided into control group and observation group,with 63 cases in each group.The control group was treated with oral use of Silibinin Capsules,and the observation group was treated with oral use of Erhuang Quzhi Granules on the basis of treatment for the control group.The course of treatment lasted for 3 months.Before and after treatment,the two groups were observed in the changes of fatty liver index,and the levels of inflammatory factors of interleukin 6(IL-6)and tumor necrosis factor alpha(TNF-α),liver function and blood lipid indicators of alanine aminotransferase(ALT),aspartate aminotransferase(AST),γ-glutamyl transpeptidase(GGT),total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C)and low-density lipoprotein cholesterol(LDL-C),and autophagy-related genes of autophagy-related gene 7(ATG7)and myosin-like BCL2 binding protein(Beclin 1).After treatment,the clinical efficacy and safety of the two groups were evaluated.Results(1)After 3 months of treatment,the total effective rate of the observation group was 90.48％(57/63),and that of the control group was 71.43％(45/63).The intergroup comparison(tested by chi-square test)showed that the efficacy of the observation group was significantly superior to that of the control group(P＜0.01).(2)After treatment,the fatty liver index of the two groups was significantly decreased compared with that before treatment(P＜0.05),and the decrease of fatty liver index in the observation group was significantly superior to that in the control group(P＜0.01).(3)After treatment,the serum levels of inflammatory factors of IL-6 and TNF-α in the two groups were significantly lower than those before treatment(P＜0.05),and the decrease of serum IL-6 and TNF-α levels in the observation group was significantly superior to that in the control group(P＜0.05).(4)AAfter treatment,the serum levels of liver function indicators of ALT,AST and GGT in the two groups were significantly lower than those before treatment(P＜0.05),and the decrease of serum ALT,AST and GGT levels in the observation group was significantly superior to that in the control group(P＜0.05).(5)After treatment,the serum levels of blood lipids of TG,TC and LDL-C in the two groups were significantly lower than those before treatment(P＜0.05),and the serum HDL-C level was significantly higher than that before treatment(P＜0.05).The decrease of serum TG,TC and LDL-C levels and the increase of serum HDL-C level in the observation group were significantly superior to those in the control group(P＜0.05).(6)After treatment,the serum levels of autophagy-related genes of ATG7 and Beclin 1 in the two groups were significantly higher than those before treatment(P＜0.05),and the increase of serum ATG7 and Beclin 1 levels in the observation group was significantly superior to that in the control group(P＜0.05).(7)During the medication,no liver or kidney function damage or serious adverse reactions were found in the two groups.Conclusion Erhuang Quzhi Granules combined with Silibinin Capsules are effective for the treatment of NAFLD patients with phlegm blended with blood stasis type,which is helpful to relieve the symptoms of fatty liver,reduce the levels of inflammatory factors,improve liver function and blood lipid levels,and regulate the expression of autophagy-related genes.

Objective To explore the clinical characteristics of patients with alcoholic liver disease(ALD)of various traditional Chinese medicine(TCM)syndrome types.Methods A retrospective analysis was conducted in 129 patients with alcoholic liver disease who met the inclusion and exclusion criteria in Foshan Hospital of Traditional Chinese Medicine from 2018 to 2022.The general data of the patients as well as their TCM syndrome types and clinical information of liver and kidney function,blood lipid,liver transient elastography during the hospital visit were collected.The distribution of TCM syndrome types in ALD patients was analyzed,and the clinical characteristics of the ALD patients with various TCM syndrome types were explored.Results(1)Of the 129 patients,128(99.22%)were male and only one(0.78%)was female,the average age was(48.71±11.50)years old,and the average body mass index(BMI)was(23.82±3.98)kg·m-2.(2)Damp-heat accumulation syndrome was most common syndrome type in ALD patients,with a total of 70 cases(54.26%),and then came liver depression and spleen deficiency syndrome(24 cases,18.60%),internal obstruction of phlegm-damp syndrome(22 cases,17.05%),liver-kidney sufficiency syndrome(7 cases,5.43%),phlegm interweaved with blood stasis syndrome(3 cases,2.33%),and internal accumulation of blood stasis syndrome(3 cases,2.33%).(3)The analysis of clinical characteristics by non-parametric rank sum test showed that there were no statistically significant differences in BMI,alcohol consumption,aspartate aminotransferase(AST),gamma-glutamyltransferase(GGT),total bilirubin(TBIL),alkaline phosphatase(ALP),triglyceride(TG),liver stiffness measurement(LSM),and controlled attenuation parameter(CAP)which reflects the fat content of liver in ALD patients with various TCM syndrome types(P＜0.05 or P＜0.01).The prominent features were as follows:patients with the 4 types of liver depression and spleen deficiency,internal obstruction of phlegm-damp,phlegm interweaved with blood stasis,and internal accumulation of blood stasis had a BMI exceeding the standard(＞24 kg·m-2),whereas patients with damp-heat accumulation syndrome and liver-kidney deficiency syndrome,which accounted for 54.26%of the sample size,had a BMI within the normal range(23.03 kg·m-2 and 21.42 kg·m-2,respectively),and the BMI of these two types differed from that(26.44 kg·m-2)of the internal obstruction of phlegm-damp syndrome(P＜0.01),suggesting that more than half of the ALD patients had the normal BMI;moreover,the patients with internal obstruction of phlegm-damp also had the highest values of serum TG(2.69 mmol/L)and CAP(292 db/m)except for the highest BMI,indicating that patients with internal obstruction of phlegm-damp syndrome had a more serious degree of obesity and hepatic fat infiltration than those with other syndrome types;the levels of AST and GGT,which separately reflect the chronic inflammatory injury of liver and bile duct cell injury,were significantly increased in the patients with damp-heat accumulation syndrome and liver-kidney deficiency syndrome,and the LSM value of these two types of patients was also the highest in all of the syndrome types,the differences being all statistically significant(P＜0.05 or P＜0.01).Conclusion Damp-heat accumulation syndrome is the main TCM syndrome type of ALD patients,the degree of fatty infiltration of the liver and overweight of ALD patients are not corresponded to the severity of illness,and there are some differences in the clinical indicators of ALD patients with various TCM syndrome types.However,with cross reference to the data of the four diagnostic examinations of TCM and the clinical indicators,the accuracy of the TCM diagnosis of ALD is expected to be increased.

The effects of oenothein B(OEB) on the proliferation, apoptosis, invasion, and migration of breast cancer MCF-7 and MDA-MB-231 cells were investigated by cell culture in vitro, network pharmacology, and molecular docking. In vitro cell experiments revealed that OEB inhibited the proliferation and colony formation ability, and promoted the apoptosis and formation of apoptotic bodies in breast cancer cells, as well as inhibited the invasion and migration of breast cancer cells. The targets of OEB were obtained using SwissTargetPrediction database and breast cancer targets were obtained from GeneCards. The targets of OEB and breast cancer were entered separately in Venny 2.1 software to obtain the Venn diagram of common targets of OEB and breast cancer. The common targets of OEB and breast cancer were input into STRING database to construct a protein-protein interaction(PPI) network, which was entered into Cytoscape 3.7.2 software for network topology analysis. Key targets were screened according to protein association strength, and analyzed for KEGG pathway enrichment. Molecular docking of OEB to key targets using AutoDock software revealed that OEB stably bound to the active pocket of P53, while OEB promoted the expression of P53 protein. MCF-7 and MDA-MB-231 cell viability and migration ability increased after silencing P53, and this change was reversed after treatment with OEB. Therefore, this study showed that OEB inhibited the proliferation, migration, and invasion of breast cancer MCF-7 and MDA-MB-231 cells, and promoted the apoptosis of breast cancer MCF-7 and MDA-MB-231 cells, which may be related to the targeted regulation of P53.
Humans ; Female ; Cell Proliferation ; Breast Neoplasms/drug therapy* ; Tumor Suppressor Protein p53/genetics* ; Molecular Docking Simulation

OBJECTIVE: To derive the Chinese medicine (CM) syndrome classification and subgroup syndrome characteristics of ischemic stroke patients. METHODS: By extracting the CM clinical electronic medical records (EMRs) of 7,170 hospitalized patients with ischemic stroke from 2016 to 2018 at Weifang Hospital of Traditional Chinese Medicine, Shandong Province, China, a patient similarity network (PSN) was constructed based on the symptomatic phenotype of the patients. Thereafter the efficient community detection method BGLL was used to identify subgroups of patients. Finally, subgroups with a large number of cases were selected to analyze the specific manifestations of clinical symptoms and CM syndromes in each subgroup. RESULTS: Seven main subgroups of patients with specific symptom characteristics were identified, including M3, M2, M1, M5, M0, M29 and M4. M3 and M0 subgroups had prominent posterior circulatory symptoms, while M3 was associated with autonomic disorders, and M4 manifested as anxiety; M2 and M4 had motor and motor coordination disorders; M1 had sensory disorders; M5 had more obvious lung infections; M29 had a disorder of consciousness. The specificity of CM syndromes of each subgroup was as follows. M3, M2, M1, M0, M29 and M4 all had the same syndrome as wind phlegm pattern; M3 and M0 both showed hyperactivity of Gan (Liver) yang pattern; M2 and M29 had similar syndromes, which corresponded to intertwined phlegm and blood stasis pattern and phlegm-stasis obstructing meridians pattern, respectively. The manifestations of CM syndromes often appeared in a combination of 2 or more syndrome elements. The most common combination of these 7 subgroups was wind-phlegm. The 7 subgroups of CM syndrome elements were specifically manifested as pathogenic wind, pathogenic phlegm, and deficiency pathogens. CONCLUSIONS There were 7 main symptom similarity-based subgroups in ischemic stroke patients, and their specific characteristics were obvious. The main syndromes were wind phlegm pattern and hyperactivity of Gan yang pattern.
Humans ; Syndrome ; Ischemic Stroke ; Medicine, Chinese Traditional ; Liver ; Phenotype