Stroke, a major cerebrovascular disease, has high morbidity and mortality. Effective methods to reduce the risk and improve the prognosis are lacking. Currently, uric acid (UA) is associated with the pathological mechanism, prognosis, and therapy of stroke. UA plays pro/anti-oxidative and pro-inflammatory roles in vivo. The specific role of UA in stroke, which may have both neuroprotective and damaging effects, remains unclear. There is a U-shaped association between serum uric acid (SUA) levels and ischemic stroke (IS). UA therapy provides neuroprotection during reperfusion therapy for acute ischemic stroke (AIS). Urate-lowering therapy (ULT) plays a protective role in IS with hyperuricemia or gout. SUA levels are associated with the cerebrovascular injury mechanism, risk, and outcomes of hemorrhagic stroke. In this review, we summarize the current research on the role of UA in stroke, providing potential targets for its prediction and treatment.
Humans ; Uric Acid/metabolism* ; Stroke/drug therapy* ; Animals ; Hyperuricemia/drug therapy* ; Ischemic Stroke/blood* ; Biomarkers/blood*

ChuanWu (CW), the dried mother root of Aconitum carmichaelii Debx., is a well-known traditional Chinese medicine (TCM) recognized for its potent efficacy but inherent toxicity, primarily due to its alkaloid content. Traditional and modern detoxification methods for CW include proper processing, rational compatibility, and specialized decoction techniques, among which honey-boiled CW is particularly distinctive. However, research on the detoxification mechanism of honey-boiled CW remains limited. This study investigated this mechanism by analyzing alkaloid transformation and supramolecular aggregation. Honey-boiled and water-boiled CW preparations were compared. Ultra-high-performance liquid chromatography-tandem mass spectrometry was used to analyze CW alkaloids, specifically diester alkaloids (DDAs), monoester alkaloids (MDAs), and non-esterified diterpenoid alkaloids (NDAs). Transmission electron microscopy was employed to observe and identify supramolecular aggregates in the honey-boiled CW decoction. In vivo absorption of water-boiled, honey-boiled, and NADES-boiled CW was compared. Median lethal dose (LD₅₀) tests assessed toxicity, including hepatotoxicity and nephrotoxicity. In vitro experiments evaluated the safety, anti-inflammatory, and analgesic effects of CW-medicated serum on RAW264.7 cells, with in vivo validation in mice. Results showed that honey promoted the conversion of highly toxic DDAs to less toxic MDAs and prevented MDAs from hydrolyzing into NDAs. Honey-boiled CW formed approximately 250 nm supramolecular aggregates that encapsulated MDAs, inhibiting their conversion to NDAs. These encapsulated MDAs acted as a stable delivery system with higher bioavailability than free benzoylmesaconine. Subsequent mouse experiments confirmed that honey-boiled CW significantly increased the LD₅₀ of CW while reducing hepatotoxicity and nephrotoxicity. Additionally, honey-boiled CW significantly improved cell safety and enhanced anti-inflammatory and analgesic effects. Our findings reveal that honey-boiled CW exhibits a potent detoxification mechanism by influencing alkaloid transformation and facilitating the formation of supramolecular aggregates. This study lays the groundwork for developing detoxification or synergistic strategies within honey-boiled TCM.

Objective:To discuss the expression of Rh family C glycoprotein(RHCG)in the esophageal squamous cell carcinoma(ESCC)tissue and its effect on the malignant biological behavior of ESCC cells,and to clarify the value of RHCG as a diagnostic and prognostic marker for the ESCC patients.Methods:A total of 143 ESCC tissue samples and 105 adjacent normal tissue samples were collected.Using immunohistochemical staining method,141 ESCC samples were divided into two groups:RHCG low expression group(immunohistochemistry score≤6)and RHCG high expression group(immunohistochemistry score>6).Immunohistochemical method was used to detect the RHCG protein expression in 143 ESCC tissues and 105 normal tissues,and the relationship between the clinicopathological characteristics of the ESCC patients was analyzed.Receiver operating characteristic(ROC)curve and Kaplan-Meier survival analysis were used to evaluate the value of RHCG in diagnosis and prognosis of the ESCC patients;univariate and multivariate COX regression analysis were used to determine the independent risk factors affecting the prognosis of the ESCC patients.Gene Expression Profiling Interactive Analysis(GEPIA2)database was used to analyze the expression of RHCG mRNA in various tumor tissues.The ESCC TE-1 cells were cultured and transfected in to 6-well cell culture plates with different Lipofectamine2000∶RHCG ratios;the cells in RHCG transfection group were transfected with weights of 2.0,2.5,and 3.0 μg for 24 and 48 h,respectively,and the cells in NC group transfected with empty vector as control.Western blotting method was used to detect the RHCG protein expression level in the TE-1 cells in various groups after transfection at different concentrations and verify the optimal transfection conditions;cell counting kit-8(CCK-8)assay was used to detect the proliferation activities of the TE-1 cells;plate clone formation assay was used to detect the colony formation numbers of the TE-1 cells;Transwell chamber assay was used to detect the numbers of migrating TE-1 cells.Results:Compared with adjacent normal tissue,the RHCG gene expression level in various cancer tissues including ESCC,glioblastoma multiforme,and head and neck squamous cell carcinoma was significantly decreased(P<0.05).RHCG protein was mainly located on the cell membrane of normal esophageal squamous epithelial cells;the RHCG protein expression intensity in ESCC tissues was lower than that in adjacent normal esophageal tissue(χ2=109.373,P<0.001),and the patients in RHCG low expression group had poorer differentiation than those in RHCG high expression group(P=0.041).The area under the curve(AUC)value of RHCG for diagnosing ESCC was 0.86,with sensitivity and specificity of 95.1%and 75.0%,respectively;the Kaplan-Meier survival analysis results showed that compared with high RHCG expression group,the patients in low RHCG expression group had shorter survival time and poorer prognosis[harard ratio(HR)=0.269,95%confidence interval(CI):0.113-0.639,P=0.020];the COX regression analysis results showed that low RHCG expression could serve as an independent risk factor affecting the prognosis of ESCC[HR=4.569,95%CI=1.315-15.877,P=0.017)].The Western blotting results verified that the optimal transfection condition was 3.0 μg RHCG plasmid for 48 h,at which time RHCG overexpression was optimal and RHCG protein expression level was highest.The CCK-8 assay results showed that compared with control group,the proliferation activity in RHCG overexpression group was decreased on the 4th day after cell seeding(P<0.001).In the TE-1 cells,the colony formation number of the TE-1 cells in RHCG over-expression group was lower than that in control group(t=17.70,P<0.001).The Transwell chamber assay results showed that compared with control group,the number of migrating cells in RHCG over-expression group was decreased(t=23.74,P<0.001).Conclusion:RHCG expression is decreased in ESCC tissues and associated with poor prognosis in ESCC patients;overexpression of RHCG can inhibit the proliferation and migration of the TE-1 cells,providing a theoretical basis for RHCG as a novel diagnostic and prognostic marker and therapeutic target for ESCC.

Objective:To investigate the clinicopathological features and differential diagnosis of eosinophilic vacuolated tumor (EVT).Methods:Seven cases of EVT with characteristic morphology and unequivocal diagnosis from the Affiliated Hospital of Qingdao University (6 cases), Qingdao, China and the 971 Hospital of PLA Navy (1 case), Qingdao, China between January 2010 and December 2021 were subject to morphological and immunohistochemical analyses. Additionally, whole exome sequencing (WES) was performed in two cases. Twenty-two cases of renal oncocytoma (RO) and 17 cases of eosinophilic chromophobe renal cell carcinoma (eChRCC) diagnosed at the same time were used as controls.Results:Four males and three females with a mean age of 42 years (range: 29-61 years) were included in the study. The tumors were nodular and well-circumscribed, with sizes ranging from 1.5 to 4.5 cm. On cross-section, they appeared gray-red or gray-white, solid, and soft. Tumor cells were arranged in nests, solid sheets, and acinar or small vesicular structures. These cells exhibited eosinophilic cytoplasm with large, prominent clear vacuoles and round nuclei with prominent nucleoli. Perinuclear halos were focally present in four cases, while small tumor cells with sparse cytoplasm and hyperchromatic nuclei were seen in one case. No necrosis or mitosis was noted. Edematous stroma was detected in three cases. All tumors were positive for CD117 and Cathepsin K, but negative for vimentin and CK7. CK20 was positive in scattered individual cells, and Ki-67 positivity ranged from 1% to 4%. Point mutations in MTOR were identified in both patients who were subject to the molecular analysis. Statistical differences in the expression of Cathepsin K, CD10, S-100A1, and Cyclin D1 between EVT and RO ( P<0.05) were significant, so were the differences in the expression of Cathepsin K, CD10, CK7 and claudin 7 between EVT and eChRCC ( P<0.001). Seven patients were followed up for 4 to 96 months (mean, 50 months), with no recurrences or metastases. Conclusions:EVT is a rare renal tumor that shares morphological and immunophenotypic features with RO and eChRCC, and it is closely linked to the TSC/MTOR pathway. The presence of large prominent transparent vacuoles in eosinophilic cytoplasm along with conspicuous nucleoli is its key morphological characteristics. The use of combined immunohistochemical stains greatly aids in its diagnosis. Typically, the tumor exhibits indolent biological behaviors with a favorable prognosis.

Objective To study the relationship between waist-to-height ratio(WHtR)and new-onset cerebral infarction in the elderly with hypertension.Methods A total of 9 096 elderly hypertensive patients were enrolled from the Kailuan study population.Using the first occurrence of cerebral infarction as the endpoint event,a prospective cohort study was performed.According to the WHtR value of the subjects with an interval of 0.05,the subjects were divided into G1 group(WHtR＜0.45),G2 group(0.45≤WHtR＜0.50),G3 group(0.50≤WHtR＜0.55),and G4 group(WHtR≥0.55).The cumulative incidence rate of endpoint event in each population were statistically analyzed using the life table method.Cox proportional hazards regression analysis was used to explore the role of WHtR in the occurrence of new cerebral infarction.Model 1 was a single factor Cox proportional hazards analysis model,only considering the influence of WHtR on the risk of cerebral infarction.After adjusting sex,age,body weight,serum hypersensitive C-reactive protein,systolic blood pressure,serum triglycerides,smoking history,fasting blood glucose,alcohol consumption,high-density lipoprotein cholesterol,diastolic blood pressure,exercise,low-density lipoprotein cholesterol,educational level,antihypertensive drug history,model 2 was established to observe the influence of WHtR on the occurrence of new-onset cerebral infarction.Results The follow-up lasted(9.3±2.7)years.Compared to the G2 group,multivariate Cox proportional hazards regression model showed that the hazard ratio HR(95%CI)for cerebral infarction in model 1 was 1.00(0.67～1.50),1.29(1.05～1.60)and 1.36(1.12～1.66)respectively in G1,G3 and G4;and that in model 2 was 1.09(0.72～1.65),1.24(0.99～1.54)and 1.31(1.05～1.62)respectively in G1,G3 and G4.Conclusion The risk of cerebral infarction in the elderly with hypertension is the lowest when WHtR between 0.45≤WHtR＜0.50,and WHtR greater than or equal to 0.55 is associated with an increased risk of new-onset cerebral infarction.

Objective:To study the predictive role of tumor burden score (TBS) for tumor recurrence after radical resection in patients with hepatocellular carcinoma (HCC).Methods:Clinical data of 202 patients with HCC undergoing radical surgery at the 900th Hospital of Joint Logistics Support Force of the Chinese People's Liberation Army, between January 2015 and December 2017 were retrospectively analyzed, including 128 males and 74 females, aged (53.66±11.93) years old. The receiver operating characteristic (ROC) curve was used to assess the accuracy of TBS in predicting postoperative tumor recurrence. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors influencing postoperative tumor recurrence. A nomogram was established and validated using calibration curves and the C-index. Kaplan-Meier survival analysis was utilized to compare survival differences between the two patient groups.Results:The area under the ROC curve for TBS in predicting postoperative tumor recurrence in HCC patients was 0.779 (95% CI: 0.717-0.842), with an optimal cutoff value of 6.2. Univariate analysis revealed that factors such as hepatitis B virus DNA level >500 IU/ml, larger maximum tumor dia-meter, and TBS>6.2 were significant risk factors for postoperative tumor recurrence (all P<0.05). Multivariate analysis further indicated that TBS>6.2 ( OR=3.60, 95% CI: 1.081-12.012, P=0.037) and maximum tumor diameter ( OR=1.240, 95% CI: 1.034-1.487, P=0.020) were independent risk factors for postoperative recurrence. Based on these risk factors, a nomogram model was established, achieving a C-index of 0.788. Kaplan-Meier survival analysis showed a better postoperative overall survival and recurrence-free survival of the low TBS group compared to those of the high TBS group (all P<0.05). Conclusion:TBS can serve as a predictive indicator for the recurrence after radical resection in patients with HCC. Both TBS and tumor size are independent risk factors for postoperative recurrence. The nomogram model can be used for predicting recurrence following radical resection in HCC patients.

Objective:To compare the mid-term clinical effects of AngioJet rheolytic thrombectomy assisted catheter-directed thrombolysis (ART+CDT) with catheter-directed thrombolysis (CDT) in the treatment of acute deep venous thrombosis of lower extremities.Methods:Ninety-one patients admitted to the Department from Jan 2016 to Dec 2017 were placed with inferior vena cava filters and divided into ART+CDT group (30 cases)and CDT group (61 cases). Total urokinase dosge, thrombolytic time, operative cost, length of hospital stay, detumescence rate, thrombus clearance rate, cumulative patency rate of lower limb veins, Villalta score at 2 years and 5 years, thrombosis recurrence rate and chronic venous insufficiency quality of life questionnaire were compared between the two groups.Results:The success rate of surgery was 100% in both groups, there was no mortality. There were significant differences in the short-term postoperative outcomes between the two groups in terms of total dosage of urokinase, thrombolysis time, total cost of surgery, length of hospital stay, detumescence rate, venous patency scores before and after treatment, and venous patency rate (all P<0.05). For the mid- and long-term postoperative outcomes of 2 and 5 years, there were no significant differences in the incidence of PTS, recurrence rate of thrombus, chronic venous function scale, and cumulative patency rate at 2 years (all P>0.05). Conclusions:ART+CDT has a significant advantage over CDT alone in terms of early efficacy and early reopening of blood flow in patients. Both ART+CDT and CDT have a low incidence of PTS and a low recurrence rate of thrombus in the mid-term follow-up, and both have satisfactory performance in the mid- and long-term efficacy of interventional treatment of deep venous thrombosis of lower limbs.

Objective:To investigate whether prophylactic use of metal clips is necessary after cold snare polypectomy (CSP) of colorectal polyps of 6-10 mm.Methods:A total of 200 patients with 6-10 mm polyps that met the criteria of cold snare resection in Chengdu Third People's Hospital from 15 February 2022 to 30 May 2022 were randomly divided into two groups: a group that received preventive metal clip treatment and an observation group. Age, gender, body mass index (BMI), Boston score, endoscopy entry time, wound size, operation time, intraoperative bleeding time, postoperative delayed bleeding rate and cost between the two groups were compared and analyzed.Results:Ninety-eight patients in the metal clip group had 122 polyps removed, and 97 patients in the observation group had 119 polyps removed. There was no significant difference in the age, gender, BMI, Boston score, endoscopy entry time or wound size between the two groups. There were significant differences in the operation time (171.03±90.78 s VS 69.81±43.26 s, t=2.266， P=0.010), intraoperative bleeding time (19.98±17.37 s VS 29.16±17.56 s, t=-2.875， P=0.006) and surgery cost (571.63±110.92 yuan VS 366.32±13.2 yuan, t=18.102， P<0.001) between the metal clip group and the observation group. There was no significant difference in the delayed bleeding incidence［0.0%（0/98）VS 1.0%（1/97）， P=0.497］between the two groups. Conclusion:For patients with continuous bleeding time <60 seconds after CSP of 6-10 mm colonic polyps, the prophylactic use of metal clips may reduce the bleeding time, but may increase the operation time and cost. Metal clips have little effect on preventing postoperative complications.

Primary lung cancer， as one of the most commonly diagnosed malignancies and the top leading cause of cancer death worldwide， has seriously endangered human life. In China， due to regional differences， although the impact of lung cancer on different regions is different， it still has the highest mortality among malignant tumors. Western medicine often has certain limitations in the treatment of lung cancer. At present， the combination of western medicine and traditional Chinese medicine （TCM） or the direct application of TCM has become an inevitable trend in the treatment of lung cancer. TCM treatment is guided by the holistic view， which includes the view of integration of the five internal organs and the integration of the body and spirit. Therefore， the treatment of lung cancer in TCM emphasizes that although the disease is located in one organ， the whole body should be treated， which corresponds to the theory of the view of integration of the five internal organs. In addition to the lung in the treatment of lung cancer， the spleen and kidney should also be treated. The lung， spleen， and kidney correspond to metal， earth， and water， respectively on the five elements. According to the generation relationship of the five elements， since earth generates metal and metal generates water， earth is the mother of metal and water is the child of metal. Therefore， benefiting fire （kidney） can replenish earth. Tonifying the mother and son of the lung can treat lung diseases， reflecting mutual generation and transformation and ceaseless generation and transformation. Long-term consumption of Qi by lung cancer can affect mother-organ. In the context of disorder of child-organ affecting mother-organ， mother-organ should be tonified in the face of deficiency. The treatment principle of banking up earth to generate metal should be followed to reinforce healthy Qi and treat the root. Effulgent earth can promote the generation of metal and the syndrome of lung deficiency can be resolve. The lung and kidney deficiency is an important factor in the incidence of lung cancer. Yin deficiency for a long time can hinder the generation of water by metal， resulting in failure of water in moistening metal， so both mother organ and child organ should be tonified. The treatment principle of mutual generation between metal and water should be employed to moisten the kidney and lung， thereby facilitating the vigorous ventilation and descending of the lung. The spleen is the mother organ of the lung， and the kidney is the child organ of the lung. Long-term lung cancer causes the deficiency of the mother and child organs， so the treatment principle of replenishing fire to nourish earth should be adopted to benefit the kidney and tonify the spleen. Therefore， innate basis and acquired foundation are both filled， and the lung can be regulated properly. When the lung， spleen， and kidney are harmonized， the generation and transformation of Qi and blood are active， and the Yin and Yang of Qi and blood are balanced， so the self-rehabilitation ability of the body is ensured， and the treatment of lung cancer will achieve a good curative effect. According to the holistic view of TCM， the whole body should be regulated to treat lung cancer. The lung， spleen， and kidney are all treated in the treatment of lung cancer. With the lung， spleen， and kidney as the central axis， the treatment principles of banking up earth to generate metal， replenishing fire to nourish earth， and mutual generation between metal and water should be followed in the treatment of lung cancer， and a good therapeutic effect can be achieved.

Ginsenoside Compound K (CK) has anti-cancer and anti-inflammatory pharmacological activities. It has not been isolated from natural ginseng and is mainly prepared by deglycosylation of protopanaxadiol. Compared with the traditional physicochemical preparation methods, the preparation of CK by hydrolysis with protopanaxadiol-type (PPD-type) ginsenoside hydrolases has the advantages of high specificity, environmental-friendliness, high efficiency and high stability. In this review, the PPD-type ginsenoside hydrolases were classified into three categories based on the differences in the glycosyl-linked carbon atoms of the hydrolase action. It was found that most of the hydrolases that could prepare CK were PPD-type ginsenoside hydrolase type Ⅲ. In addition, the applications of hydrolases in the preparation of CK were summarized and evaluated to facilitate large-scale preparation of CK and its development in the food and pharmaceutical industries.
Ginsenosides/pharmacology* ; Hydrolases ; Sapogenins/chemistry*