Objective:To investigate the risk factors for adverse outcomes in elderly patients with nonvalvular atrial fibrilla-tion(AF)after percutaneous left atrial appendage closure(LAAC)combined with radiofrequency ablation(RFA).Meth-ods:A total of 199 elderly AF patients who admitted in Department of Cardiology,Yuhuangding Hospital between Jan 1st,2019 and Aug 17th,2023 and underwent LAAC combined RFA were enrolled.The patients were divided into case group(n=78)and control group(n=121)according to presence of atrial arrhythmia and/or cerebral infarction(CI)within one year after operation.Baseline clinical data,laboratory indexes and color Doppler ultrasound indexes were compared be-tween the two groups,and multivariate Logistic regression was used to analyze the risk factors for postoperative atrial ar-rhythmia and/or CI.Receiver operating characteristic(ROC)curve was constructed to analyze the predictive efficacy of risk factors for atrial arrhythmia and/or CI after operation.Results:Univariate analysis indicated that compared with pa-tients in control group,those in case group had significant higher proportions of preoperative persistent atrial fibrillation(52.60％ vs.37.20％),old myocardial infarction(OMI)(11.50％vs.1.70％)and left atrial diameter(LAD)[(45.47±6.90)mm vs.(43.34±6.64)mm](P＜0.05 or＜0.01).Multivariate Logistic regression analysis indicated history of OMI(OR=8.736,95％CI 1.772～43.069,P=0.008)and LAD(OR=1.053,95％CI 1.006～1.102,P=0.027)were independent risk factors of adverse outcomes in elderly AF patients after LAAC+RFA.ROC analysis indicated that predic-tive efficacy of combined detection of OMI and LAD(AUC=0.663,95％CI 0.593～0.728)for adverse outcomes within 1 year in elderly AF patients after LAAC+RFA was significantly better than those of OMI(AUC=0.549,95％CI 0.477～0.620)and LAD(AUC=0.602,95％CI 0.531～0.671)alone(Z=3.045,2.312,P=0.002,0.021).Conclusion:His-tory of old myocardial infarction and left atrial diameter are independent risk factors for atrial arrhythmia and/or cerebral infarction within 1 year after percutaneous left atrial appendage closure combined with radiofrequency ablation in elderly patients with atrial fibrillation,and the combination has good predictive performance.

Objective:To investigate the risk factors for adverse outcomes in elderly patients with nonvalvular atrial fibrilla-tion(AF)after percutaneous left atrial appendage closure(LAAC)combined with radiofrequency ablation(RFA).Meth-ods:A total of 199 elderly AF patients who admitted in Department of Cardiology,Yuhuangding Hospital between Jan 1st,2019 and Aug 17th,2023 and underwent LAAC combined RFA were enrolled.The patients were divided into case group(n=78)and control group(n=121)according to presence of atrial arrhythmia and/or cerebral infarction(CI)within one year after operation.Baseline clinical data,laboratory indexes and color Doppler ultrasound indexes were compared be-tween the two groups,and multivariate Logistic regression was used to analyze the risk factors for postoperative atrial ar-rhythmia and/or CI.Receiver operating characteristic(ROC)curve was constructed to analyze the predictive efficacy of risk factors for atrial arrhythmia and/or CI after operation.Results:Univariate analysis indicated that compared with pa-tients in control group,those in case group had significant higher proportions of preoperative persistent atrial fibrillation(52.60％ vs.37.20％),old myocardial infarction(OMI)(11.50％vs.1.70％)and left atrial diameter(LAD)[(45.47±6.90)mm vs.(43.34±6.64)mm](P＜0.05 or＜0.01).Multivariate Logistic regression analysis indicated history of OMI(OR=8.736,95％CI 1.772～43.069,P=0.008)and LAD(OR=1.053,95％CI 1.006～1.102,P=0.027)were independent risk factors of adverse outcomes in elderly AF patients after LAAC+RFA.ROC analysis indicated that predic-tive efficacy of combined detection of OMI and LAD(AUC=0.663,95％CI 0.593～0.728)for adverse outcomes within 1 year in elderly AF patients after LAAC+RFA was significantly better than those of OMI(AUC=0.549,95％CI 0.477～0.620)and LAD(AUC=0.602,95％CI 0.531～0.671)alone(Z=3.045,2.312,P=0.002,0.021).Conclusion:His-tory of old myocardial infarction and left atrial diameter are independent risk factors for atrial arrhythmia and/or cerebral infarction within 1 year after percutaneous left atrial appendage closure combined with radiofrequency ablation in elderly patients with atrial fibrillation,and the combination has good predictive performance.

OBJECTIVE: A new three-dimensional(3D) classification of posterior cruciate ligament (PCL) tibial avulsion fracture based on computed tomography(CT) features was established and the significance in clinical treatment was explored in this study. METHODS: From May 2013 to November 2023, 43 cases of PCL tibial avulsion fracture in the Second Hospital of Jilin University were analyzed retrospectively, including 29 males and 14 females, aged (34.3±8.5) years. According to traditional Meyers and McKeever classification, 3 cases were typeⅠ;2 cases of typeⅡ;38 cases were type Ⅲ. Based on the characteristics of CT images, 43 patients were given specific treatment strategies and followed up to evaluate the curative effect. According to the degree of fracture displacement, involved range and the integrity of fracture block demonstrated by CT images, the new three-dimensional classification of PCL avulsion fracture was established. Kappa coefficient was used for consistency test. RESULTS: A new 3D classification of PCL tibial avulsion fracture was established. TypeⅠwas the non-displaced fracture (displacement degree ≤3 mm), in which typeⅠa was the avulsion range limited in the posterior intercondylar fossa, and Ib was the avulsion range beyond the posterior intercondylar fossa. TypeⅡrepresented the displaced fracture in the posterior intercondylar fossa (avulsion limited to the posterior intercondylar fossa and fracture displacement>3 mm), in which typeⅡa represented a slight displacement with a intact broken block and the posterior elevation of the avulsion (hinge mechanism), typeⅡb represented the complete separation of fracture ends with a intact fracture block, and typeⅡc was the comminuted fracture. Type Ⅲ was the displaced fracture beyond the posterior intercondylar fossa (avulsion involving the articular surface of the tibial plateau or the intercondylar ridge and the degree of displacement > 3 mm), among which type Ⅲa was the simple fracture with intact broken block, type Ⅲb represented the comminuted fracture, and type Ⅲc was the complex fracture with tibial plateau fracture. According to this new 3D classification, 43 patients were classified as type Ia in 2 cases and typeⅠb in 1 case;typeⅡa in 2 cases, typeⅡb in 15 cases and typeⅡc in 7 cases;type Ⅲa in 2 cases, type Ⅲb in 5 cases and type Ⅲc in 9 cases. All the 43 cases in this study achieved bone union. At the last follow-up, according to the hospital for special surgery knee score(HSS)evaluation system for the knee joint function, 27 cases were excellent, 11 cases were good, 5 cases were fair. The average Kappa value of inter-observer reliability in the first stage was 0.793, and the second stage was 0.855. The average Kappa value of the whole stage was 0.839, indicating high level of consistency. The average Kappa value of intra-observer reliability was 0.893, indicating high level of consistency. CONCLUSION The 3D classification of PCL tibial avulsion fracture is intuitive, demonstrating a high level of reliability. It has a certain guiding significance for the selection of clinical treatment methods, and it is suggested to be promoted and applied as a new classification system in clinical practice.
Humans ; Male ; Female ; Posterior Cruciate Ligament/surgery* ; Adult ; Tibial Fractures/classification* ; Tomography, X-Ray Computed ; Middle Aged ; Retrospective Studies ; Fractures, Avulsion/classification* ; Imaging, Three-Dimensional ; Young Adult

OBJECTIVE: Gastric cancer (GC) is one of the most common malignancies seen in clinic and requires novel treatment options. Morin is a natural flavonoid extracted from the flower stalk of a highly valuable medicinal plant Prunella vulgaris L., which exhibits an anti-cancer effect in multiple types of tumors. However, the therapeutic effect and underlying mechanism of morin in treating GC remains elusive. The study aims to explore the therapeutic effect and underlying molecular mechanisms of morin in GC. METHODS: For in vitro experiments, the proliferation inhibition of morin was measured by cell counting kit-8 assay and colony formation assay in human GC cell line MKN45, human gastric adenocarcinoma cell line AGS, and human gastric epithelial cell line GES-1; for apoptosis analysis, microscopic photography, Western blotting, ubiquitination analysis, quantitative polymerase chain reaction analysis, flow cytometry, and RNA interference technology were employed. For in vivo studies, immunohistochemistry, biomedical analysis, and Western blotting were used to assess the efficacy and safety of morin in a xenograft mouse model of GC. RESULTS: Morin significantly inhibited the proliferation of GC cells MKN45 and AGS in a dose- and time-dependent manner, but did not inhibit human gastric epithelial cells GES-1. Only the caspase inhibitor Z-VAD-FMK was able to significantly reverse the inhibition of proliferation by morin in both GC cells, suggesting that apoptosis was the main type of cell death during the treatment. Morin induced intrinsic apoptosis in a dose-dependent manner in GC cells, which mainly relied on B cell leukemia/lymphoma 2 (BCL-2) associated agonist of cell death (BAD) but not phorbol-12-myristate-13-acetate-induced protein 1. The upregulation of BAD by morin was due to blocking the ubiquitination degradation of BAD, rather than the transcription regulation and the phosphorylation of BAD. Furthermore, the combination of morin and BCL-2 inhibitor navitoclax (also known as ABT-737) produced a synergistic inhibitory effect in GC cells through amplifying apoptotic signals. In addition, morin treatment significantly suppressed the growth of GC in vivo by upregulating BAD and the subsequent activation of its downstream apoptosis pathway. CONCLUSION Morin suppressed GC by inducing apoptosis, which was mainly due to blocking the ubiquitination-based degradation of the pro-apoptotic protein BAD. The combination of morin and the BCL-2 inhibitor ABT-737 synergistically amplified apoptotic signals in GC cells, which may overcome the drug resistance of the BCL-2 inhibitor. These findings indicated that morin was a potent and promising agent for GC treatment. Please cite this article as: Wang Y, Sun XY, Ma FQ, Ren MM, Zhao RH, Qin MM, Zhu XH, Xu Y, Cao ND, Chen YY, Dong TG, Pan YF, Zhao AG. Morin inhibits ubiquitination degradation of BCL-2 associated agonist of cell death and synergizes with BCL-2 inhibitor in gastric cancer cells. J Integr Med. 2025; 23(3): 320-332.
Humans ; Flavonoids/therapeutic use* ; Stomach Neoplasms/pathology* ; Animals ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Cell Line, Tumor ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Ubiquitination/drug effects* ; Mice ; Drug Synergism ; Mice, Inbred BALB C ; Mice, Nude ; Xenograft Model Antitumor Assays ; Flavones

Objective:The aim of this study is to explore the correlation among serum hepcidin,ferritin,and q-Dioxn MRI with upgrading,upstaging and biochemical recurrence in prostate cancer(PCa)patients.Methods:A total of 103 PCa patients di-agnosed by biopsy were selected for this study.All patients underwent q-Dixon MRI prior to biopsy for T2*value measurement.Then serum hepcidin and ferritin were measured before receiving radical prostatectomy.Pathological grading and staging were conducted both preoperatively and postoperatively.The correlations among hepcidin,ferritin,T2*values,and postoperative upgrading,upstaging,biochemical recurrence were subsequently analyzed.Results:The hepcidin level of PCa patients was measured at(123.51±23.03)ng/mL,while the ferritin level was recorded at(239.80±79.59)ng/mL,and the T2* value was(41.07±6.37)ms.A total of 49 and 36 cases were observed with upgrading and upstaging in postoperative pathology,respectively.The median follow-up duration was 28.0 months(6.0-38.0 months),during which biochemical recurrence was observed in 12 cases.For upgrading,hep-cidin and ferritin demonstrated the predictive efficacy,with areas under the ROC curve of 0.777 and 0.642,respectively,whereas T2*values did not show sufficient predictive power.For upstaging,hepcidin,ferritin,and T2*exhibited predictive efficacy,with areas under the ROC curve of 0.806,0.696,and 0.655,respectively.Multivariate Logistic regression analysis indicated that hepcidin served as an independent risk factor for both upgrading(OR 1.055,95％CI 1.027-1.085,P＜0.001)and upstaging(OR 1.094,95％CI 1.040-1.152,P＜0.001).Cox regression analysis showed that hepcidin(95％CI 1.000-1.052,P=0.049)was a sig-nificant risk factor for predicting biochemical recurrence.Conclusion:Hepcidin could serve as a predictor for pathological upgra-ding,upstaging and biochemical recurrence after radical prostatectomy,which provides a novel potential index for risk stratification and prognostic evaluation of PCa patients.

Objective To investigate the toxicokinetic differences of 3,4-methylenedioxy-N-methylamphetamine(MDMA)and its metabolite 4,5-methylene dioxy amphetamine(MDA)in rats af-ter single and continuous administration of MDMA,providing reference data for the forensic identifica-tion of MDMA.Methods A total of 24 rats in the single administration group were randomly divided into 5,10 and 20 mg/kg experimental groups and the control group,with 6 rats in each group.The ex-perimental group was given intraperitoneal injection of MDMA,and the control group was given intraperi-toneal injection of the same volume of normal saline as the experimental group.The amount of 0.5 mL blood was collected from the medial canthus 5 min,30 min,1 h,1.5 h,2 h,4 h,6 h,8 h,10 h,12 h after administration.In the continuous administration group,24 rats were randomly divided into the experi-mental group(18 rats)and the control group(6 rats).The experimental group was given MDMA 7 d by continuous intraperitoneal injection in increments of 5,7,9,11,13,15,17 mg/kg per day,respectively,while the control group was given the same volume of normal saline as the experimental group by in-traperitoneal injection.On the eighth day,the experimental rats were randomly divided into 5,10 and 20 mg/kg dose groups,with 6 rats in each group.MDMA was injected intraperitoneally,and the con-trol group was injected intraperitoneally with the same volume of normal saline as the experimental group.On the eighth day,0.5 mL of blood was taken from the medial canthus 5 min,30 min,1 h,1.5 h,2 h,4 h,6 h,8 h,10 h,12 h after administration.Liquid chromatography-triple quadrupole tandem mass spectrometry was used to detect MDMA and MDA levels,and statistical software was employed for data analysis.Results In the single-administration group,peak concentrations of MDMA and MDA were reached at 5 min and 1 h after administration,respectively,with the largest detection time limit of 12 h.In the continuous administration group,peak concentrations were reached at 30 min and 1.5 h af-ter administration,respectively,with the largest detection time limit of 10 h.Nonlinear fitting equations for the concentration ratio of MDMA and MDA in plasma and administration time in the single-administration group and continuous administration group were as follows:T=10.362C-1.183,R2=0.974 6;T=7.397 3C-0.694,R2=0.961 5(T:injection time;C:concentration ratio of MDMA to MDA in plasma).Conclusions The toxicokinetic data of MDMA and its metabolite MDA in rats,obtained through single and continuous administration,including peak concentration,peak time,detection time limit,and the relationship between concentration ratio and administration time,provide a theoretical and data foundation for relevant forensic identification.

Abstract: Chigger mites belong to the phylum Arthropoda, class Arachnida, sub-class Acari, order Parasitiformes, family Trombiculidae and Leeuwenhoekiidae, with a wide range of species. There are more than 3 700 known species of mites globally, of which 531 species in 46 genera from three sub-families have been recorded in China, and 320 species of chigger mites recorded from 3 subfamilies and 32 genera in Yunnan Province. At this stage, chigger mites are the only vectors of scrub typhus, with about 60 species worldwide being potential vectors. Six vectorial mite species have been confirmed in China, including Leptotrombidium deliense, L.scutellare, L.rubellum, L.sialkotense, L.kaohuense, L.insulare. Yunnan Province has reported five vectorial mite species, including the previously-mentioned five species except for L.sialkotense. The zoogeographic study divided Yunnan Province into 5 zoogeographic areas, namely, Central Hengduan Mountains subregion, Southern Hengduan Mountains subregion, Eastern Yunnan Plateau subregion, Western Yunnan Plateau subregion, Southern Yunnan Mountainous subregion. The Southern Hengduan Mountains subregion has the highest number of known genera and species of scrub typhus and the highest number of scrub typhus cases, with 216 species in 22 genera from 3 subfamilies, and all 5 species of vector scrub typhus were distributed. Southern Yunnan Mountain subregion has the least number of mite species, with 91 species in 12 genera from three sub-families, with L. scutellare being the dominant vectorial mite species across the province. Due to suitable natural geographic conditions in Yunnan Province, vectorial mites can propagate rapidly, leading to a large number of scrub typhus cases. According to statistics, the number of scrub typhus cases in Yunnan Province has rapidly increased, with 15.40 times, 20.64 times and 28.91 times more cases in 2016, 2017 and 2018 respectively than in 2006. Scrub typhus remains a serious public health problem in Yunnan Province, posing a threat to the health of the local population. Therefore, prevention and control efforts should continue to focus on the affected areas and the general public.

Objective:To construct the nursing quality evaluation index system for Laryngeal Cancer Rehabilitation Nursing Clinic.Methods:The nursing quality evaluation index system for Laryngeal Cancer Rehabilitation Nursing Clinic was constructed through literature analysis and survey research. From October to December 2022, 17 experts were selected for two rounds of expert consultation, and indicators at all levels were screened, modified, and improved to establish the nursing quality evaluation index system for Laryngeal Cancer Rehabilitation Nursing Clinic.Results:In the two rounds of expert consultation, the effective response rate of the questionnaire was 100.0% (17/17), and the expert authority coefficients were 0.912 and 0.924, respectively. The Kendall harmony coefficients of the two rounds of consultation were 0.199 and 0.221, respectively ( P<0.05). The final constructed nursing quality evaluation index system for Laryngeal Cancer Rehabilitation Nursing Clinic included 3 primary indicators, 15 secondary indicators, and 90 tertiary indicators. Conclusions:The nursing quality evaluation index system for Laryngeal Cancer Rehabilitation Nursing Clinic is scientific and reliable, providing reference for nursing quality evaluation and standardized management of Laryngeal Cancer Rehabilitation Nursing Clinic.

Objective To look for a tissue paraffin embedding method that can replace xylene transparent agent. Methods The mixture of N-butanol and turpentine was used to replace the role of anhydrous ethanol and xylene in the process of conventional paraffin embedding. The brain, kidney, stomach, liver and duodenum of multiple cerebral infarction model rats were embedded in paraffin. Finally, the new dehydration procedure was evaluated according to the effect of paraffin section, HE staining and immunohistochemical result . Results The mixture of N-butanol and turpentine could replace not only the dehydration effect of anhydrous ethanol but also the transparency effect of xylene in the conventional paraffin embedding process. The tissue sections treated with the mixture of N-butanol and turpentine were smooth, and the tissue did not become brittle or hard; After HE staining, the nucleus and cytoplasm of the new dehydrated tissue were distinct, and the chromaticity, color and transparency of the tissue were not different from those of the conventional dehydration procedure; Immunohistochemical staining was performed on different tissues of rats, and the comparison result were no different from conventional embedded tissue immunohistochemical staining. Conclusion N-butanol combined with turpentine for tissue dehydration can not only avoid the toxic effect of xylene on human, but also reduce the tissue damage caused by excessive dehydration of anhydrous alcohol.

Based on the field investigations in 91 investigation sites (counties) in southwest China between 2001 and 2019, the present paper reported the chigger mites on A. agrarius mice in southwest China for the first time by using a series of statistical methods. From 715 striped field mice captured in 28 of 91 investigated sites, only 255 chiggers were collected, and they were identified as 14 species, 6 genera in 3 subfamilies under 2 families. Of 715 A. agrarius mice, only 24 of them were infested with chigger mites with low overall prevalence (PM=3.4%), overall mean abundance (MA=0.36 mites/host) and overall mean intensity (MI=10.63 mites/host). The species diversity and infestation of chiggers on A. agrarius were much lower than those previously reported on some other rodents in southwest China. On a certain species of rodent, A. agrarius mouse in southwest China seems to have a very low susceptibility to chigger infestations than in other geographical regions. Of 14 chigger species, there were 3 dominant species, Leptotrombidium sialkotense, L. rupestre and Schoengastiella novoconfuciana, which were of aggregated distribution among different individuals of A. agrarius hosts. L. sialkotense, one of 6 main vectors of scrub typhus in China, was the first dominant on A. agrarius. The species similarity of chigger mites on male and female hosts was low with CSS=0.25, and this reflects the sex-bias of different genders of A. agrarius mice in harboring different chigger species.