Guided by the theories of yin-yang and collateral disease， this paper identifies the dysregulation of yang qi ascent and descent as the core pathomechanism of hypertension. Based on clinical experience， a treatment approach centered on the method of raising yang and promoting descent was proposed. Clinically， three major syndrome types were identified. Firstly， deficiency of zong qi （ancestral qi） with blood stasis， obstruction of phlegm-turbidity and blood stasis， and hyperactivity of liver yang. Corresponding empirical formulation， Yizong Huoxue Decoction （益宗活血汤） was applied to tonify zong qi， invigorate blood， and raise yang. Secondly， Lizong Huoxue Decoction （理宗活血汤） was used to resolve phlegm， promote yang qi circulation， and regulate qi and blood. Thirdly， Qinggan Tongluo Decoction （清肝通络饮） was used to clear the liver， dredge collaterals， and subdue hyperactive yang. For special types such as non-dipper hypertension， time-specific syndrome differentiation and treatment can be applied based on a thorough understanding of the underlying pathomechanism， aiming to provide new insights into clinical diagnosis and treatment of hypertension.

BACKGROUND: Double-stranded RNA-specific adenosine deaminase 1 (ADAR1) binds to double-stranded RNA and catalyzes the deamination of adenosine (A) to inosine (I). The functional mechanism of ADAR1 in non-small cell lung cancer (NSCLC) remains incompletely understood. This study aimed to investigate the prognostic significance of ADAR1 in NSCLC and to elucidate its potential role in regulating tumor cell proliferation and migration. METHODS: Data from The Cancer Genome Atlas (TCGA) and cBioPortal were analyzed to assess the correlation between high ADAR1 expression and clinicopathological features as well as prognosis in lung cancer. We performed Western blot (WB), cell proliferation assays, Transwell invasion/migration assays, and nude mouse xenograft modeling to examine the phenotypic changes and molecular mechanisms induced by ADAR1 knockdown. Furthermore, the ADAR1 p150 overexpression model was utilized to validate the proposed mechanism. RESULTS: ADAR1 expression was significantly elevated in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) tissues compared with adjacent non-tumor tissues (LUAD: P=3.70×10-15, LUSC: P=0.016). High ADAR1 expression was associated with poor prognosis (LUAD: P=2.03×10-2, LUSC: P=2.81×10-2) and distant metastasis (P=0.003). Gene Set Enrichment Analysis (GSEA) indicated that elevated ADAR1 was associated with mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway activation, matrix metalloproteinase-9 (MMP-9) expression, and cell adhesion. ADAR1 and MMP-9 levels showed a strongly positive correlation (P=6.45×10-34) in 10 lung cancer cell lines, highest in H1581. Knockdown of ADAR1 in H1581 cells induced a rounded cellular morphology with reduced pseudopodia. Concomitantly, it suppressed cell proliferation, invasion, migration, and in vivo tumorigenesis. It also suppressed ERK phosphorylation and downregulated cellular Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog (c-FOS), MMP-9, N-cadherin, and Vimentin. Conversely, ADAR1 p150 overexpression in PC9 cells enhanced ERK phosphorylation and increased c-FOS and MMP-9 expression. CONCLUSIONS High ADAR1 expression is closely associated with poor prognosis and distant metastasis in NSCLC patients. Mechanistically, ADAR1 may promote proliferation, invasion, migration, and tumorigenesis in lung cancer cells via the ERK/c-FOS/MMP-9 axis.
Humans ; Lung Neoplasms/physiopathology* ; Adenosine Deaminase/genetics* ; Matrix Metalloproteinase 9/genetics* ; Cell Proliferation ; Carcinoma, Non-Small-Cell Lung/physiopathology* ; Cell Movement ; Animals ; Mice ; RNA-Binding Proteins/genetics* ; Female ; Male ; Cell Line, Tumor ; Proto-Oncogene Proteins c-fos/genetics* ; Middle Aged ; MAP Kinase Signaling System ; Gene Expression Regulation, Neoplastic ; Mice, Nude ; Extracellular Signal-Regulated MAP Kinases/genetics*

Objective:To distinguish Hedyotis diffusa Willd. and its common countrerfeit, Hedyotis corymbosa. and Hedyotis tenelliflora. by analyzing and comparing their macroscopical identification, microscopic character and HPLC fingerprints. Methods:The features of macroscopical identification, microscopic character including cross-sections of stem, leaf, fruit and seed, and herbal powders were observed in the three samples by traditional methods. The difference of chromatographic peaks among the three samples were also analyzed by HPLC methods.Results:The stems of Hedyotis diffusa Willd. were cylindrical, and the capsules were solitary or double born in the leaf axils, oblate, 2-3 mm in diameter, with a long petiole; the Hedyotis corymbosa. and Hedyotis tenelliflora. were tetragonal, and the Hedyotis corymbosa. was 2-5 capsules born in leaf axils in corymbose inflorescences, globular, 1-1.5 mm in diameter, with a slender petiole; the Hedyotis tenelliflora. were 1-3 capsules clustered in the leaf axils, ovoid with longitudinal ribs around the margin, about 1.5 mm in diameter, without the long petiole, about 1.5 mm in diameter, sessile, the edge of the leaf drying revolute long needle-like. Under the identification, the cross section of the Hedyotis diffusa Willd. stem was almost round, the middle vein of the leaves was protrusion below, the inner pericarp fiber layer consisted of two layers of fiber cells, the surface of the seed coat cells was polygon, and the wall was densely covered with small reddish brown or yellow-brown warty spots. The cross section of the Hedyotis corymbosa. stem was quadrilateral, the surface of the seed coat cell was polygon, the wall was wavy and curved, and there was no warty point on the wall. The middle veins of the Hedyotis tenelliflora. were slightly sunken in the upper part, but not protruding in the lower part; the endocarp fiber layer consisted of 8 to 13 layers of fiber cells. Moreover, the HPLC fingerprint analysis demonstrated substantial dissimilarities in the characteristic peaks of these herbs. Conclusion:The traditional and modern analysis technology show that there are some differences in the characteristics, microscopical cross section, the powder characteristics, which can effectively distinguish the Hedyotis diffusa Willd. and its two local varieties.

Humans ; Gastrointestinal Microbiome ; Constipation/therapy* ; Probiotics/therapeutic use* ; Patients

Objective:To observe any effect of using the KidGo exoskeleton rehabilitation robot on the lower limb motor function of children with spastic cerebral palsy.Methods:Thirty children with spastic cerebral palsy were sorted at random into a control group and a robotics group, each of 15. Both groups received conventional rehabilitation 5 days a week for 12 weeks, but the robotics group also spent 30 minutes daily training with the KidGo exoskeleton robot. Before and after the intervention, the lower limb muscle tone and strength, gross motor function, balance, and functional independence of both groups were assessed using surface electromyography, a handheld muscle strength tester, the gross motor function measure, the Berg Balance Scale, and the Wee-functional independence measure.Results:After the intervention great improvements in average lower limb muscle tone and strength, gross motor function, balance, and functional independence were observed in both groups, but the improvements in the robotics group were significantly greater, on average.Conclusion:Supplementing conventional rehabilitation with training using the KidGo exoskeleton rehabilitation robot can better improve muscle tone, strength, gross motor functioning, balance, and the functional independence of children with spastic cerebral palsy.

ObjectiveTo observe the clinical efficacy and safety of Chinese herbal enema combined with fumigation as adjunctive therapy for non-dialysis chronic kidney disease （CKD） patients of stage 3-5 with spleen-kidney yang deficiency and turbid toxin blood stasis pattern. MethodsA total of 120 non-dialysis CKD，patients of stage 3-5 with spleen-kidney yang deficiency and turbid toxin blood stasis pattern were randomly divided into treatment group and control group， with 60 cases in each group. The control group received conventional western medical treatment， while the treatment group additionally received Chinese herbal enema combined with fumigation， with enema and fumigation performed alternately， once every other day， three times a week. The treatment course for both groups was 4 weeks. The levels of serum creatinine （Scr）， estimated glomerular filtration rate （eGFR）， and the total score of traditional Chinese medicine symptoms were compared before and after treatment in both groups. The efficacy of traditional Chinese medicine symptoms and clinical efficacy were compared between the two groups after treatment. Adverse reactions in both groups were observed during the treatment period. ResultsThe total score of traditional Chinese medicine symptoms was significantly reduced after treatment in both groups （P＜0.01）. Compared to the control group after treatment， the treatment group showed significant decreases in Scr and the total score of traditional Chinese medicine symptoms， and a significant increase in eGFR （P＜0.05）. The total effective rate of traditional Chinese medicine symptoms in the treatment group （96.67%） was higher than that in the control group （46.67%， P＜0.01）， as well as the total effective rate of clinical efficacy in the treatment group （75.00%） versus that in the control group （28.33%， P＜0.01）. During the treatment period， the vital signs of patients in both groups remained stable， and there were no significant abnormalities in blood routine， urine routine， stool routine， liver function indicators， and electrocardiogram after treatment. ConclusionChinese herbal enema combined with fumigation as adjunctive therapy can significantly alleviate clinical symptoms， improve renal function， and demonstrate good safety for non-dialysis CKD patients of stage 3-5 with spleen-kidney yang deficiency and turbid toxin blood stasis pattern.

Objective We aimed to observe the effect of the traditional Chinese medicine(TCM)-based"tertiary hospital-community integrated"treatment program in patients with diabetic kidney disease.Methods A total of 126 patients from the Jiangtai and Cuigezhuang Communities in Chaoyang District were randomly divided into the experimental group and the control group(n=63 patients per group).In the experimental group,the"tertiary hospital-community integrated"treatment program was implemented(including TCM differentiated health preservation,chronic disease management,comprehensive diagnosis and treatment program of integrated Chinese and Western medicine),while in the control group,the existing chronic disease diagnosis,treatment,and management program in the community was implemented(including chronic disease management with regular follow-ups,diagnosis and treatment program of Western medicine).The observation period was 6 months,with 3 months as a course of treatment.The 24 h urine total protein level(24 hUTP),the serum level of creatinine(Scr),and the estimated glomerular filtration rate(eGFR)were compared between the two groups,as well as the effective rates of 24 hUTP,Scr,and eGFR,the rate of achieving standard glucose levels and normal lipid metabolism,including low-density lipoprotein-cholesterol(LDL-C),triglyceride(TG),and glycosylated hemoglobin(GHB),the level of patients'self-management,and the medical service in utilization.Results There were 120 patients included for analysis(60 in the experimental group and 60 in the control group).The difference in 24 hUTP was significantly different(P＜0.05),while Scr and eGFR were not statistically different between the experimental and control groups after 3 months of treatment.The differences in 24 hUTP,Scr,and eGFR were statistically significant after 6 months(P＜0.05).After 6 months of treatment in both groups,the effective rates of 24 hUTP,Scr,and eGFR were higher in the experimental group than in the control group(78.3％,48.3％,and 50.0％in the experimental group and 35.0％,18.3％,and 15.0％in the control group,respectively)(P＜0.05);after 6 months,the LDL-C,TG,and GHB qualified rates were higher in the experimental group than in the control group(75.0％,83.3％,and 71.7％in the experimental group and 56.7％,63.3％,and 46.7％in the control group,respectively;P＜0.05);comparing the self-management levels of the two groups after 3 and 6 months of treatment,the total self-management score and the total self-efficacy score were both higher in the experimental group than in the control group(P＜0.05);comparing the time of hospitalization and hospitalization costs of the two groups 6 months after enrollment,the time of hospitalization and hospitalization costs were lower in the experimental group(P＜0.05).Conclusion The"tertiary hospital-community integrated"TCM-based treatment program improves renal function,glucose and lipid metabolism,and patients'self-management;it can reduce the economic burden of families,save medical resources,and improve the utilization of medical services.

Objective:To evaluate the effects of different imaging frequencies and matching strategies of cone-beam computed tomography (CBCT) on dose-volume parameters in target and organs at risk (OAR) during image-guided radiotherapy for prostate cancer.Methods:A total of 561 sets of CBCT images from 21 patients treated with radical prostate radiotherapy who were admitted to Peking University First Hospital from June 2022 to May 2023 were retrospectively analyzed. All patients received volumetric intensity modulated arc therapy (VMAT) at a prescribed dose of 70 Gy divided into 25 times, 2.8 Gy per time. Clinical target volume (CTV) and OAR were delineated by the same oncologist on each CBCT image. The planned CT (pCT) was rigorously registered to CBCT after calibration of positioning errors according to different image guidance modes and frequencies, and CT values and structures were propagated to CBCT through deformable image registration (DIR). The daily dose was mapped to pCT according to the deformation vector field (DVF) for dose accumulation. The actual cumulative dose of daily online CBCT validation was compared with the weekly CBCT validation regimen (days 1, 2, 3, 6, 11, 16 and 21 online imaging). The dosimetric comparison was also made between bone-based matching and soft tissue-based matching (after automatic bone-based matching, manual prostate-based matching was performed and fine-tuning was made regarding the anterior wall of rectum). Wilcoxon signed rank-sum test was utilized to analyze dose-volume parameters between planned and cumulative doses that exhibited non-normal distribution, while paired t-test was employed for assessing shift values and average dose parameters that demonstrated normal distribution. Results:Compared with daily CBCT image guidance, the CTV_D 98% in weekly CBCT was significantly reduced [(69.08±1.58) vs. (65.24±3.64) Gy, P<0.001]. The CTV_D 98% of bone-based matching was (69.27±2.14) Gy, but the high-dose volume of the rectum were significantly increased: V 60 Gy was 3.18%±3.10%, V 65 Gy was 0.77%±1.23%. The target area coverage using soft tissue-based matching is sufficient, with a CTV_D 98% of (69.08±1.58) Gy. And the percentage volume of high-dose volume of the rectum was significantly reduced, with V 60 Gy being 2.02%±2.42% and V 65 Gy being 0.34%±0.68%. Conclusions:In prostate cancer patients undergoing moderately-fractionated radiotherapy, daily CBCT image guidance demonstrates superior target coverage compared to a weekly scheme. Soft tissue-based matching, which is automatic bone-based matching followed by manual soft tissue-based matching and fine-tuning according to the anterior rectal wall, offers better rectal protection while maintaining target coverage.

ObjectiveTo observe the effects of Yuejuwan in the treatment of psychological and heart diseases （PHD） and explore its mechanism. MethodThirty 6-week-old healthy male SPF AopE^-/- mice and 10 homologous C57BL/6J mice were selected for the experiment. The 30 AopE^-/- mice were divided into a model group， low-dose （7.58 g·kg^-1·d^-1） and high-dose （30.32 g·kg^-1·d^-1） Yuejuwan groups， with 10 mice in each group， and 10 C57BL/6J mice were assigned to the blank control group. Intragastrical administration lasted 12 weeks. During feeding， the PHD model was induced by chronic unpredictable mild stress （CUMS） combined with high-fat diet in mice. After intragastric administration， the behavioral results ［open field test （OFT） and sucrose preference test （SPT）］ of mice in each group， the content of aspartic transaminase （AST）， alanine aminotransferase （ALT）， 5-hydroxytryptamine （5-HT）， noradrenaline （NE）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， total cholesterol （TC）， and triglyceride （TG） in serum of mice detected by the automatic biochemical analyzer， the oil red O staining and HE staining of aorta and liver and Masson staining of myocardial tissues were used for model evaluation. Finally， liver TMT-labeled quantitative proteomics was used to explore the mechanism of action. ResultThe model mice showed obvious manifestations of depression， anxiety， loss of interest， and despair， manifest lipid deposition in the aorta and liver by pathological observation， and increased myocardial fibrosis in myocardial tissues. After intragastric administration of Yuejuwan， the above symptoms and indexes of the PHD model mice were improved. Compared with the blank control group， the model group showed decreased standing times， cumulative time in the central area， total moving distance， moving speed， and sucrose preference at week 12 （P<0.01）. Compared with the model group， the Yuejuwan groups showed decreased indexes mentioned above （P<0.01）. After sample collection， AST， ALT， and TG levels in the model group were higher （P<0.01） and the levels of 5-HT， NE， and HDL-C were lower than those in the blank control group （P<0.01）. The results of liver TMT labeled quantitative proteomics suggested that the PHD model mainly caused the changes in protein expression levels such as ApoE， UGT1A5， and FASN in mice，involving acetyl CoA metabolism，response to bacteria，cellular amino acid catabolism， and other processes，which were related to the abnormal metabolic function of the liver. The efficacy of Yuejuwan against PHD was achieved mainly through the regulation of high mobility group nucleosomal-binding domain 2 （HMGN2）， CALD1， and Mup7 protein expression levels and correcting the biological processes and abnormal pathways related to the pathogenesis of PHD，including muscle contraction，tight junction pathway，myocardial contraction pathway，and focal adhesion pathway. ConclusionCUMS combined with high-fat diet is reasonable in the induction of the PHD model in AopE^-/- mice. Yuejuwan can correct the depression and anxiety conditions of PHD model mice，reduce the aortic plaque， and recover the abnormal blood lipid and liver function levels. Furthermore， Yuejuwan can correct abnormal biological processes and pathways of PHD model mice. The differential proteins screened throughout the experiment and the involved physiological and pathological changes are the focus of the next experiment.