OBJECTIVE To explore the effect and mechanism of Zhiqiao gancao decoction （ZQGCD） on pathological angiogenesis of degenerative intervertebral disc. METHODS The rats were randomly divided into sham operation group （normal saline）， model group （normal saline）， hypoxia inducible factor-1α （HIF-1α） inhibitor （YC-1） group [2 mg/（kg·d）， tail vein injection]， and ZQGCD low-dose， medium-dose and high-dose groups [3.06， 6.12， 12.24 g/（kg·d）]， with 8 rats in each group. Except for sham operation group， lumbar disc degeneration model of rat was constructed in all other groups. After modeling， they were given relevant medicine once a day， for consecutive 3 weeks. After the last medication， pathological changes and angiogenesis of the intervertebral disc tissue in rats were observed； the levels of inflammatory factors [interleukin-1β （IL-1β）， IL-6， tumor necrosis factor-α （TNF-α）] and the expressions of angiogenesis-related proteins [HIF-1α， vascular endothelial growth factor （VEGF）， VEGF receptor 2 （VEGFR2）， angiotensin 1（Ang 1）， Ang 2] in the com intervertebral disc tissue in rats were all determined. In cell experiment， the primary nucleus pulposus cells were isolated and cultured from rats， and cellular degeneration was induced using 50 ng/mL TNF-α. The cells were divided into blank control group （10% blank control serum）， TNF-α group （10% blank control serum）， YC-1 group （10% blank control serum+0.2 mmol/L YC-1）， and 5%， 10%， 15% drug-containing serum group （5%， 10%， 15% drug-containing serum）. After 24 hours of intervention， the nucleus pulposus cells were co-cultured with HUVEC. The expressions of Collagen Ⅱ， matrix metalloproteinase-3 （MMP-3） in nucleus pulposus cells were detected. HUVEC proliferation， migration and tube forming ability were detected， and the expression levels of the HIF-1α/VEGF/Ang signal axis and angiogenesis- related proteins （add MMP-2， MMP-9） in HUVEC were detected. RESULTS Animal experiments had shown that compared with model group， the positive expression of CD31 in the intervertebral disc tissues of rats in each drug group was down-regulated （P＜ 0.05）， the levels of inflammatory factors and angiogenesis-related proteins were decreased significantly （P＜0.05）， and the pathological changes in the intervertebral disc were alleviated. Cell experiments had shown that compared with TNF-α group， the expression of Collagen Ⅱ in nucleus pulposus cells of all drug groups was significantly up-regulated （P＜0.05）， and the expression of MMP-3 was significantly down-regulated （P＜0.05）； the proliferation， migration and tubulogenesis of HUVEC were significantly weakened （P＜0.05）. The mRNA and protein expressions of HIF-1α， VEGF， Ang 2 as well as the expression of angiogenesis-related proteins （except for the expression of Ang 2 mRNA and HIF-1α， VEGFR2， Ang 2 protein in 5% drug- containing serum group） were significantly down-regulated （P＜0.05）. CONCLUSIONS ZQGCD may inhibit the HIF-1α/VEGF/ Ang signal axis to weaken the angiogenic ability of vascular endothelial cells， improve pathological angiogenesis in the intervertebral disc， and delay the degeneration of the intervertebral disc.

Objective To explore the value of oral contrast-enhanced ultrasonography (OCEUS) combined with contrast-enhanced CT in predicting preoperative T staging in patients with gastric cancer. Methods A retrospective analysis was conducted on 80 patients with gastric cancer confirmed via endoscopic biopsy or postoperative pathology at the First People’s Hospital of Jining from January 2021 to November 2024. The cohort included 56 males and 24 females, aged 38-79 years, with a median age of 55.9 years. All patients underwent both OCEUS and contrast-enhanced CT within one week prior to surgery. T staging of gastric cancer was determined using OCEUS, contrast-enhanced CT, or their combination. The results were compared with pathological T staging, and statistical differences in accuracy were analyzed. Results Pathological T staging identified T1 in 9 cases, T2 in 16 cases, T3 in 42 cases, and T4 in 13 cases. OCEUS indicated T1 in 6 cases, T2 in 14 cases, T3 in 50 cases, and T4 in 10 cases, with an accuracy rate of 80.0%. Contrast-enhanced CT indicated T1 in 4 cases, T2 in 12 cases, T3 in 52 cases, and T4 in 12 cases, with an accuracy rate of 75.0%. The combination of OCEUS and contrast-enhanced CT indicated T1 in 6 cases, T2 in 15 cases, T3 in 47 cases, and T4 in 12 cases, with an accuracy rate of 87.5%. The combined approach demonstrated significantly higher accuracy in preoperative T staging compared to either method alone (P < 0.05). Conclusion The combination of OCEUS and contrast-enhanced CT improves the accuracy of preoperative T staging in gastric cancer patients, providing valuable support for their diagnosis and treatment.

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

This study investigates the pharmacokinetics and metabolic characteristics of three marine-derived piericidins as potential drug leads for kidney disease: piericidin A (PA) and its two glycosides (GPAs), glucopiericidin A (GPA) and 13-hydroxyglucopiericidin A (13-OH-GPA). The research aims to facilitate lead selection and optimization for developing a viable preclinical candidate. Rapid absorption of PA and GPAs in mice was observed, characterized by short half-lives and low bioavailability. Glycosides and hydroxyl groups significantly enhanced the absorption rate (13-OH-GPA > GPA > PA). PA and GPAs exhibited metabolic instability in liver microsomes due to Cytochrome P450 enzymes (CYPs) and uridine diphosphoglucuronosyl transferases (UGTs). Glucuronidation emerged as the primary metabolic pathway, with UGT1A7, UGT1A8, UGT1A9, and UGT1A10 demonstrating high elimination rates (30%-70%) for PA and GPAs. This rapid glucuronidation may contribute to the low bioavailability of GPAs. Despite its low bioavailability (2.69%), 13-OH-GPA showed higher kidney distribution (19.8%) compared to PA (10.0%) and GPA (7.3%), suggesting enhanced biological efficacy in kidney diseases. Modifying the C-13 hydroxyl group appears to be a promising approach to improve bioavailability. In conclusion, this study provides valuable metabolic insights for the development and optimization of marine-derived piericidins as potential drug leads for kidney disease.
Animals ; Male ; Mice ; Aquatic Organisms/chemistry* ; Biological Availability ; Cytochrome P-450 Enzyme System/metabolism* ; Glucuronosyltransferase/metabolism* ; Microsomes, Liver/metabolism* ; Molecular Structure ; Biological Products/pharmacokinetics* ; Pyridines/pharmacokinetics*

Rare inherited coagulation disorders(RCD) are defined as diseases caused by deficiency of coagulation factor/factors, other than factor Ⅷ,factor Ⅸ or von Willebrand factor.RCD are mainly autosomal recessive inheritance disorders with prevalences from 1 in 50 0000 to 1 in 200 0000.The clinical manifestations of RCD are heterogeneous, mainly characterized by bleeding, but thrombosis or no clinical manifestations can also occur. Accurate understanding and diagnosis of RCD is of great significance for clinical treatment.

Objective To investigate the effects of abdominal massage combined with electroacupuncture point-through-point method on the expressions of circadian clock genes of Clock,BMAL1,PER1 and neurotransmitters contents of ACh and Glu in insomnia rats and its possible mechanism.Methods Totally 50 SD male rats were randomly divided into normal group,model group,abdominal massage group,electroacupuncture point-through-point group and combination group,with 10 rats in each group.Except for the normal group,an insomnia rat model was established by intraperitoneal injection of p-chlorophenylalanine.Abdominal massage group received abdominal massage;electroacupuncture point-through-point group was treated with flat acupuncture,"Baihui"through"Shenting","Sanyinjiao"through"Yinlingquan"(bilateral),"Shenmen"through"Neiguan"(bilateral),the electroacupuncture instrument dilatational wave,frequency of 1 Hz/20 Hz was connected;the combination group was treated with electroacupuncture through acupoints after abdominal massage;1 time/d for each treatment group,a total of 7 days.The normal group and model group were not intervened.HE staining was used to observe the pathological changes of neurons in hypothalamic tissue,the expression of Clock,BMAL1 and PER1 mRNA were detected by RT-qPCR,the expressions of Clock,BMAL1 and PER1 in hypothalamic tissue were detected by immunohistochemical staining,the expression of Clock,BMAL1 and PER1 protein in hypothalamic tissue were detected by Western blot,the contents of ACh and Glu in serum were detected by ELISA.Results Compared with the normal group,the model group rats had a longer sleep latency,shorter sleep duration,severe damage to the cellular structure of the hypothalamic tissue,and a vacuolar like change,with a decrease in the number of neuronal cells,the expressions of Clock and BMAL1 mRNA and protein in hypothalamic tissue increased,while the expressions of PER1 mRNA and protein decreased;the contents of serum ACh and Glu increased,with statistical significance(P<0.05).Compared with the model group,the abdominal massage group,electroacupuncture point-through-point group,and combination group could all shorten the sleep latency,prolong sleep duration,and improve the morphology of hypothalamic neurons,reduce the expressions of Clock and BMAL1 mRNA and protein in hypothalamic tissue,up-regulate the expressions of PER1 mRNA and protein,and reduce the contents of serum ACh and Glu,with statistical significance(P<0.05),the combination group showed the most obvious effects(P<0.05).Conclusion Abdominal massage combined with electroacupuncture point-through-point method can improve insomnia.Its mechanism may be related to the regulation of circadian clock genes Clock,BMAL1,PER1 mRNA and protein expression,as well as neurotransmitter content.

Objective To explore the funding situation and hot research directions of NSFC(National Natural Science Foundation of China)projects in the discipline of acupoints and meridians from 1991 to 2022;To provide reference for this discipline to apply for the NSFC.Methods National Natural Science Foundation of China was login in to query website.The acupoints and meridians discipline project from 1991 to 2022 were retrieved.The project leader,project name,supporting unit,province,funding category,funding amount,keywords and other information were extracted.The data were input to Excel 2023 to establish a database,and descriptive analysis of project funding situation was performed.Target keywords were extracted,and the word table was classified and uploaded to the micro-word cloud online to draw the word cloud map to analyze the research hotspots.Results From 1991 to 2022,the number of projects funded by the NSFC for acupoints and meridians was 173.The funding category was mainly general projects,and the supporting units were mainly TCM colleges and universities and scientific research institutions.The main research directions were meridian essence,acupoint-viscera/body related effects and mechanism of action,and the signal molecules and related pathways were the entry points.Conclusion From 1991 to 2022,the NSFC-funded acupoints and meridians disciplines are mainly based on general projects,mainly concentrated in scientific research institutions and TCM colleges and universities,with uneven regional distribution.The essence of meridians and collaterals,acupoints-viscera/body-related effects and mechanisms(mechanisms)are the key research directions.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective To develop an evidence-based practice program for ICU eye care and evaluate its application effect using Stetler model of research utilization.Methods The systematic search was carried out in domestic and foreign guid elines,systematic reviews,evidence summaries,expert consensuses on eye care for ICU patients.The quality of the included literature was evaluated and the evidence was summarized.The evidence based on expert advice,clinical context and stakeholder opinions was screened.According to Stetler model of research utilization,the evidence translation/application was formulated from 3 aspects,including method,level and type of evidence application,and the evidence translation was implemented using a stepwise trial design.Five ICUs in a tertiary hospital in Zhejiang Province were selected,and the order of enrollment of each ICU was determined by computer-generated random numbers from April to september,2022.In the first month,all ICUs were in pre-evidence-based practice period,and in the second month,an ICU was trained and entered the evidence-based practice period.Until the 6th month,all ICUs entered the evidence-based practice period.Then the rate of ocular symptoms and implementation rate of eye care measures were compared before and after EBP.Results A total of 1 540 patients were included.With regard to the implementation rate of eye care measures,the rate of lubricant use and suspected ocular infection management in patients at high risk for ocular complications in evidence-based practice period was significantly higher compared with pre-evidence-based practice period(P＜0.001),and no statistically significant difference was found in the rate of eyelid closure.The incidence of conjunctival exposure,subconjunctival hemorrhage,conjunctival congestion,and ocular discharge in non-neurology critical care patients decreased compared with pre-evidence-based practice period(P＜0.05),and the incidence of conjunctival edema and conjunctival congestion in NICU patients decreased compared with pre-evidence-based practice period as the intervention continued(P＜0.001).Conclusion Evidence-based practice in eye care for ICU patients using Stetler model of research utilization can standardize the practice of eye care for ICU patients and improve the quality of care.

Male ; Humans ; Liquid Chromatography-Mass Spectrometry ; Chromatography, Liquid ; Tandem Mass Spectrometry ; Varicocele/diagnosis* ; Biomarkers