Objective To investigate the therapeutic effect of cnithol on acute pancreatitis(AP)rats and its regulatory mechanism on phosphoinositol 3-kinase(PI3K)/protein kinase B(Akt)signaling pathway.Methods SPF-grade SD male rats were randomly divided into control group,model group(50 μg·kg-1 hyranin+10 mg·kg-1 LPS),positive control group(2 mg·kg-1 dexamethasone),experimental-L group(20 mg·kg-1 osthol)and experimental-H group(40 mg·kg-1 osthol),experimental-H+740Y-P group(40 mg·kg-1 osthol+2 mg·kg-1 PI3K activator 740Y-P),15 mice in each group.The activities of amylase and lipase in serum of rats were detected by automatic biochemical analyzer 24 h after the last administration.The levels of inflammatory factors tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)in serum,the content of malondialdehyde(MDA)and the activity of superoxide dismutase(SOD)in pancreas were detected by enzyme-linked immunosorbent assay(ELISA).Hematoxylin-eosin(HE)staining was used to observe the pathological changes of pancreatic tissue and score the pathological damage.Western blot was used to detect the expression of PI3K/Akt pathway related proteins in rat pancreas.Results The activities of serum amylase in control group,model group,positive control group,experimental-H group and experimental-H+740Y-P group were(135.67±12.89),(1 027.84±32.16),(174.31±15.27),(186.70±17.39)and(835.92±28.78)U·mL-1,respectively;the contents of TNF-α were(35.69±3.10),(223.54±15.23),(48.76±4.25),(52.31±4.68)and(208.46±13.65)pg·mL-1,respectively;the contents of MDA were(2.15±0.14),(6.37±0.42),(2.78±0.17),(2.81±0.15)and(5.96±0.36)nmol·mg-1,respectively;the histopathological injury scores were 1.12±0.07,10.23±0.38,3.14±0.21,3.25±0.23 and 9.68±0.40,respectively;p-PI3K/PI3K ratios were 0.82±0.05,1.96±0.15,1.07±0.06,1.10±0.07 and 1.69±0.14,respectively.The above indexes were compared with the control group in the model group,the positive control group,experimental-H group and the model group,and the above indexes of experimental-H+740Y-P group and experimental-H group,and the differences were statistically significant(all P＜0.05).Conclusion Gossetin can play a therapeutic role in AP,and its mechanism may be related to the inhibition of PI3K/Akt signaling pathway.

Objective To explore the protective mechanism of honey-processed Hedysari Radix in regulating intestinal mucosal injury in rats with spleen qi deficiency.Methods The three-factor composite modeling method of bitter cold diarrhea,overwork and hunger and satiety disorder was used to construct a spleen qi deficiency model rats.After the model was successfully made,they were randomly divided into model group,honey-processed Hedysari Radix group and probiotic group,with 15 animals in each group.Another 15 normal rats were taken as the blank group.The honey-processed Hedysari Radix group was given 12.6 g·kg-1 water decoction of honey-processed Hedysari Radix by gavage,the probiotics group was given Bifidobacterium Lactobacillus triple viable tablets suspension at a dose of 0.625 g·kg-1,and the blank group and the model group were given the same dose of distilled water.The rats in the four groups were administered once a day for 15 days.Enzyme-linked immunosorbent assay was used to detect diamine oxidase(DAO)in serum,D-lactic acid(D-LA),secretory immunoglobulin A factor,and Western blotting was used to detect the expression levels of AMP-activated protein kinase(AMPK),zonula occludens-1(ZO-1)and occludin in colon tissues.Results The serum levels of DAO in the blank group,model group,honey-processed Hedysari Radix group and probiotic group were(138.93±9.78),(187.95±12.90),(147.21±6.92)and(166.47±3.37)pg·mL-1;the contents of D-LA were(892.23±49.17),(1 099.84±137.64),(956.56±86.04)and(989.61±51.75)μg·L-1;the contents of SIgA in colon tissues were(14.04±1.42),(11.47±2.39),(11.84±1.49)and(12.93±1.65)μg·mL-1;the relative expression levels of ZO-1 protein in colon tissues were 1.18±0.11,0.42±0.04,0.77±0.05 and 0.95±0.07;the relative expression levels of occludin protein were 1.35±0.31,0.61±0.17,1.19±0.19 and 0.88±0.13;the relative expression levels of AMPK protein were 0.91±0.02,0.35±0.09,0.74±0.08 and 0.59±0.11.Compared with the model group,there were significant differences in the serum content of DAO and D-LA,SIgA content in colon,and the content of ZO-1,occludin and AMPK protein in the honey-processed Hedysari Radix group(P＜0.01,P＜0.05).Conclusion Honey-processed Hedysari Radix can enhance the protective effect on the intestinal mucosa of rats with spleen qi deficiency by regulating the expression of related inflammatory cytokines,intestinal mucosal upper cell enzymes and tight junction proteins in rats with spleen qi deficiency.

Objective:To examine the factors that contribute to memory impairment in elderly stroke patients and develop a predictive model.Methods:One hundred stroke patients from the First People's Hospital of Changzhou were selected to assess the incidence of memory impairment using the Montreal cognitive assessment memory index score(MoCA-MIS).Univariate analysis and multivariate Logistic regression were performed to determine the factors influencing memory impairment in these patients.Additionally, the correlation among relevant scale scores was examined, and a prediction model was developed.Results:In the study, 49 patients(49.0%)did not exhibit memory impairment.Patients with memory impairment were found to have higher proportions of individuals over 75 years old, elevated levels of triglyceride(TG), total cholesterol(TC), low-density lipoproteins cholesterol(LDL-C), and National Institute of Health Stroke Scale(NIHSS)scores compared to those without memory impairment.Conversely, patients without memory impairment had higher proportions of individuals with more than 9 years of education, higher levels of high-density lipoprotein cholesterol(HDL-C), mini-mental state examination(MMSE)scores, Rivermead behavioural memory test-Ⅱ(RBMT-Ⅱ)scores, and picture-based memory impairment screen(PMIS)scores(all P<0.05).Furthermore, Montreal cognitive assessment-memory index(MoCA-MIS)scores in stroke patients with memory impairment showed negative correlations with NIHSS scores, TG, and LDL-C, while showing positive correlations with HDL-C, MMSE scores, RBMT-Ⅱ scores, and PMIS scores(all P<0.05).Multifactorial Logistic regression analysis indicated that years of education, TG, HDL-C, NIHSS score, MMSE score, RBMT-Ⅱ score, PMIS score, and the location of the lesion in the cortex or temporal lobe were significant factors influencing memory impairment in stroke patients(all P<0.05).The receiver operating characteristic curve(ROC)analysis revealed an area under curve(AUC)of 0.955(95% CI: 0.921-0.977)for the prediction model of memory impairment in stroke patients, with a Yoden index of 0.841. Conclusions:The risk of memory impairment in stroke patients is associated with education years and blood lipid levels.Factors such as high education level, active cognitive function, and memory training serve as protective factors against memory impairment.The prediction model developed using these influencing factors demonstrates high predictive accuracy for post-stroke memory impairment.

Jumonji domain-containing protein D3(JMJD3)is a 2-oxoglutarate-dependent dioxygenase that specif-ically removes transcriptional repression marks di-and tri-methylated groups from lysine 27 on histone 3(H3K27me2/3).The erasure of these marks leads to the activation of some associated genes,thereby influencing various biological processes,such as development,differentiation,and immune response.However,comprehensive descriptions regarding the relationship between JMJD3 and inflammation are lacking.Here,we provide a comprehensive overview of JMJD3,including its structure,functions,and involvement in inflammatory pathways.In addition,we summarize the evidence supporting JMJD3's role in several inflammatory diseases,as well as the potential therapeutic applications of JMJD3 inhibitors.Additionally,we also discuss the challenges and opportunities associated with investigating the functions of JMJD3 and developing targeted inhibitors and propose feasible solutions to provide valuable insights into the functional exploration and discovery of potential drugs targeting JMJD3 for inflammatory diseases.

Objective To explore the clinical efficacy of antibiotic bone cement covered reconstruction steel plate in the treatment of infected anterior pelvic ring fracture.Methods From January 2017 to March 2022,11 patients with infected ante-rior pelvic ring fracture were treated with antibiotic bone cement covered reconstruction steel plate including 7 males and 4 fe-males and the age ranged from 27 to 49 years old.The pelvic fractures were classified according to the Tile typology:4 cases of Cl type,4 cases of C2 type,and 3 cases of C3 type.Among them,2 cases of infected anterior ring were infected after internal fixation of anterior ring,and 9 patients were infected with infected anterior ring due to incomplete early debridement,which was classified as infected according to the injury severity score(ISS)for 24 to 38 scores.The anterior ring was internally fixed by extended debridement,irrigation,and antibiotic bone cement covered reconstruction plate,and the posterior ring fractures were all closed reduction and internally fixed with sacroiliac screws.Results All 11 cases obtained follow-up from 13 to 20 months.A-mong them,2 patients had recurrence of postoperative infection,1 case was re-dissected and replaced with antibiotic bone cement-coated internal fixation,and 1 case had a milder infection without accumulation of the medullary cavity,and the infection was controlled by retaining the plate and replacing the antibiotic bone cement only after dissecting.Two cases developed incisional oozing,which healed after removal of the internal fixation three months postoperatively.All patients did not show pelvic fracture redisplacement or reinfection during the follow-up period.All 11 cases eventually healed bony.At the final follow-up,according to the Matta score,the fracture reduction was excellent in 6 cases,good in 4,and possible in 1.According to the Majeed functional score,it was excellent in 6,good in 3,and possible in 2.Conclusion Antibiotic bone cement covered reconstruction plate is ef-fective in the treatment of infected anterior pelvic ring fracture,with high intraoperative safety and low recurrence rate of infec-tion,which is conducive to the early postoperative rehabilitation and significantly shortens the course of the disease.

Objective: To investigate the effects and mechanism of interleukin-4-modified gold nanoparticle (IL-4-AuNP) on the wound healing of full-thickness skin defects in diabetic mice. Methods: Experimental research methods were adopted. Gold nanoparticle (AuNP) and IL-4-AuNP were synthesized by improving the methods described in published literature. The morphology of those two particles were photographed by transmission electron microscopy, and their particle sizes were calculated. The surface potential and hydration particle size of the two particles were detected by nanoparticle potentiometer and particle size analyzer, respectively. The clearance rate of IL-4-AuNP to hydrogen peroxide and superoxide anion was measured by hydrogen peroxide and superoxide anion kits, respectively. Mouse fibroblast line 3T3 cells were used and divided into the following groups by the random number table (the same below): blank control group, hydrogen peroxide alone group treated with hydrogen peroxide only, hydrogen peroxide+IL-4-AuNP group treated with IL-4-AuNP for 0.5 h and then treated with hydrogen peroxide. After 24 h of culture, the reactive oxygen species (ROS) levels of cells were detected by immunofluorescence method; cell count kit 8 was used to detect relative cell survival rate. The macrophage Raw264.7 mouse cells were then used and divided into blank control group and IL-4-AuNP group that treated with IL-4-AuNP. After 24 h of culture, the expression of arginase 1 (Arg-1) in cells was observed by immunofluorescence method. Twelve male BALB/c mice (mouse age, sex, and strain, the same below) aged 8 to 10 weeks were divided into IL-4-AuNP group and blank control group, treated accordingly. On the 16^th day of treatment, whole blood samples were collected from mice for analysis of white blood cell count (WBC), red blood cell count (RBC), hemoglobin level, or platelet count and the level of aspartate aminotransferase (AST), alanine transaminase (ALT), urea, or creatinine. The inflammation, bleeding, or necrosis in the heart, liver, spleen, lung, and kidney tissue of mice were detected by hematoxylin-eosin (HE). Another 36 mice were selected to make diabetic model, and the full-thickness skin defect wounds were made on the back of these mice. The wounds were divided into blank control group, AuNP alone group, and IL-4-AuNP group, with 12 mice in each group, and treated accordingly. On the 0 (immediately), 4^th, 9^th, and 15^th day of treatment, the wound condition was observed and the wound area was calculated. On the 9^th day of treatment, HE staining was used to detect the length of neonatal epithelium and the thickness of granulation tissue in the wound. On the 15^th day of treatment, immunofluorescence method was used to detect ROS level and the number of Arg-1 positive cells in the wound tissue. The number of samples was 6 in all cases. Data were statistically analyzed with independent sample t test, corrected t test, Tukey test, or Dunnett T3 test. Results: The size of prepared AuNP and IL-4-AuNP were uniform. The particle size, surface potential, and hydration particle size of AuNP and IL-4-AuNP were (13.0±2.1) and (13.9±2.5) nm, (-45.8±3.2) and (-20.3±2.2) mV, (14±3) and (16±4) nm, respectively. For IL-4-AuNP, the clearance rate to hydrogen peroxide and superoxide anion were (69±4)% and (52±5)%, respectively. After 24 h of culture, the ROS level of 3T3 in hydrogen peroxide alone group was significantly higher than that in blank control group (q=26.12, P<0.05); the ROS level of hydrogen peroxide+IL-4-AuNP group was significantly lower than that in hydrogen peroxide alone group (q=25.12, P<0.05) and close to that in blank control group (P>0.05). After 24 h of culture, the relative survival rate of 3T3 cells in hydrogen peroxide+IL-4-AuNP group was significantly higher than that in hydrogen peroxide alone group (t=51.44, P<0.05). After 24 h of culture, Arg-1 expression of Raw264.7 cells in IL-4-AuNP group was significantly higher than that in blank control group (t'=8.83, P<0.05).On the 16^th day of treatment, there were no significant statistically differences in WBC, RBC, hemoglobin level, or platelet count and the level of AST, ALT, urea, or creatinine of mice between blank control group and IL-4-AuNP group (P>0.05). No obvious inflammation, bleeding or necrosis was observed in the heart, liver, spleen, lung, and kidney of important organs in IL-4-AuNP group, and no significant changes were observed compared with blank control group. On the 0 and 4^th day of treatment, the wound area of diabetic mice in blank control group, AuNP alone group, and IL-4-AuNP group had no significant difference (P>0.05). On the 9^th day of treatment, the wound areas both in AuNP alone group and IL-4-AuNP group were significantly smaller than that in blank control group (with q values of 9.45 and 14.87, respectively, P<0.05), the wound area in IL-4-AuNP group was significantly smaller than that in AuNP alone group (q=5.42, P<0.05). On the 15^th day of treatment, the wound areas both in AuNP alone group and IL-4-AuNP group were significantly smaller than that in blank control group (with q values of 4.84 and 20.64, respectively, P<0.05), the wound area in IL-4-AuNP group was significantly smaller than that in AuNP alone group (q=15.80, P<0.05); moreover, inflammations such as redness and swelling were significantly reduced in IL-4-AuNP group compared with the other two groups. On the 9^th day of treatment, compared with blank control group and AuNP alone group, the length of neonatal epithelium in the wound of diabetic mice in IL-4-AuNP group was significantly longer (all P<0.05), and the thickness of the granulation tissue in the wound was significantly increased (with q values of 11.33 and 9.65, respectively, all P<0.05). On the 15^th day of treatment, compared with blank control group, ROS levels in wound tissue of diabetic mice in AuNP alone group and IL-4-AuNP group were significantly decreased (P<0.05). On the 15^th day of treatment, the number of Arg-1 positive cells in the wounds of diabetic mice in IL-4-AuNP group was significantly more than that in blank control group and AuNP alone group, respectively (all P<0.05). Conclusions: IL-4-AuNP is safe in vivo, and can improve the oxidative microenvironment by removing ROS and induce macrophage polarization towards M2 phenotype, thus promote efficient diabetic wound healing and regeneration of full-thickness skin defects in diabetic mice.
Mice ; Male ; Animals ; Interleukin-4 ; Gold/pharmacology* ; Diabetes Mellitus, Experimental ; Creatinine ; Hydrogen Peroxide ; Reactive Oxygen Species ; Superoxides ; Metal Nanoparticles ; Soft Tissue Injuries ; Antibodies ; Inflammation ; Necrosis ; Hemoglobins

Bufonis Venenum, an animal medicinal material, is widely used for treating cardiovascular diseases and pain induced by rheumatics or malignant tumors. In view of the high activity and high toxicity, it is of great significance to pay attention to the quality control of Bufonis Venenum to ensure the safety and effectiveness of its preparations. China's drug standards involve 102 preparations(474 batch numbers) containing Bufonis Venenum approved for sale, including 14 preparations in the Chinese Pharmacopoeia(2020 edition) and 68 preparations in the standards issued by the Ministry of Health Drug Standard of the People's Republic of China. Bufonis Venenum is mostly used in pill and powder preparations in the form of raw powder, with the main functions of clearing heat, removing toxin, relieving swelling and pain, replenishing qi, activating blood, opening orifice, and awakening brain. Except the high level of quality control for Bufonis Venenum in the preparations in the Chinese Pharmacopoeia(2020 edition), the quality control standards of Bufonis Venenum in other preparations are low or even absent. Therefore, it is urgent to conduct research on the improvement of quality standards for the preparations containing Bufonis Venenum. This study retrieved the reports focusing on the quality evaluation and quality control of the preparations containing Bufonis Venenum from CNKI, PubMed, and Web of Science. Qualitative and quantitative analysis methods for 64 preparations containing Bufonis Venenum have been reported, mainly including thin-layer chromatography, HPLC fingerprint, and multi-component content determination. The index components mainly involved bufadienolides, such as gamabufalin, arenobufagin, bufotalin, bufalin, cinobufagin, and resibufogenin. According to the literature information, this paper suggests that attention should be paid to the correlations between the analysis methods and detection indexes of medicinal materials, decoction pieces and preparations, the monitoring of indole alkaloids, and the content uniformity inspection for further improving the quality standards for the preparations containing Bufonis Venenum.
Animals ; Humans ; Bufonidae ; Powders ; Bufanolides/pharmacology* ; Quality Control ; Chromatography, High Pressure Liquid ; Pain/drug therapy*

Bone defects caused by different causes such as trauma, severe bone infection and other factors are common in clinic and difficult to treat. Usually, bone substitutes are required for repair. Current bone grafting materials used clinically include autologous bones, allogeneic bones, xenografts, and synthetic materials, etc. Other than autologous bones, the major hurdles of rest bone grafts have various degrees of poor biological activity and lack of active ingredients to provide osteogenic impetus. Bone marrow contains various components such as stem cells and bioactive factors, which are contributive to osteogenesis. In response, the technique of bone marrow enrichment, based on the efficient utilization of components within bone marrow, has been risen, aiming to extract osteogenic cells and factors from bone marrow of patients and incorporate them into 3D scaffolds for fabricating bone grafts with high osteoinductivity. However, the scientific guidance and application specification are lacked with regard to the clinical scope, approach, safety and effectiveness. In this context, under the organization of Chinese Orthopedic Association, the Expert consensus for the clinical application of autologous bone marrow enrichment technique for bone repair ( version 2023) is formulated based on the evidence-based medicine. The consensus covers the topics of the characteristics, range of application, safety and application notes of the technique of autologous bone marrow enrichment and proposes corresponding recommendations, hoping to provide better guidance for clinical practice of the technique.

Objective: To understand the current status of diagnosis and treatment of chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL) among hematologists, oncologists, and lymphoma physicians from hospitals of different levels in China. Methods: This multicenter questionnaire survey was conducted from March 2021 to July 2021 and included 1,000 eligible physicians. A combination of face-to-face interviews and online questionnaire surveys was used. A standardized questionnaire regarding the composition of patients treated for CLL/SLL, disease diagnosis and prognosis evaluation, concomitant diseases, organ function evaluation, treatment selection, and Bruton tyrosine kinase (BTK) inhibitor was used. Results: ①The interviewed physicians stated that the proportion of male patients treated for CLL/SLL is higher than that of females, and the age is mainly concentrated in 61-70 years old. ②Most of the interviewed physicians conducted tests, such as bone marrow biopsies and immunohistochemistry, for patient diagnosis, in addition to the blood test. ③Only 13.7% of the interviewed physicians fully grasped the initial treatment indications recommended by the existing guidelines. ④In terms of cognition of high-risk prognostic factors, physicians' knowledge of unmutated immunoglobulin heavy-chain variable and 11q- is far inferior to that of TP53 mutation and complex karyotype, which are two high-risk prognostic factors, and only 17.1% of the interviewed physicians fully mastered CLL International Prognostic Index scoring system. ⑤Among the first-line treatment strategy, BTK inhibitors are used for different types of patients, and physicians have formed a certain understanding that BTK inhibitors should be preferentially used in patients with high-risk factors and elderly patients, but the actual use of BTK inhibitors in different types of patients is not high (31.6%-46.0%). ⑥BTK inhibitors at a reduced dose in actual clinical treatment were used by 69.0% of the physicians, and 66.8% of the physicians had interrupted the BTK inhibitor for >12 days in actual clinical treatment. The use of BTK inhibitors is reduced or interrupted mainly because of adverse reactions, such as atrial fibrillation, severe bone marrow suppression, hemorrhage, and pulmonary infection, as well as patients' payment capacity and effective disease progression control. ⑦Some differences were found in the perceptions and behaviors of hematologists and oncologists regarding the prognostic assessment of CLL/SLL, the choice of treatment options, the clinical use of BTK inhibitors, etc. Conclusion: At present, a gap remains between the diagnosis and treatment of CLL/SLL among Chinese physicians compared with the recommendations in the guidelines regarding the diagnostic criteria, treatment indications, prognosis assessment, accompanying disease assessment, treatment strategy selection, and rational BTK inhibitor use, especially the proportion of dose reduction or BTK inhibitor discontinuation due to high adverse events.
Female ; Humans ; Male ; Aged ; Middle Aged ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy* ; Prognosis ; Lymphoma, B-Cell ; Immunohistochemistry ; Immunoglobulin Heavy Chains/therapeutic use*

Objective To observe the potential mechanism of electroacupuncture regulating the erythropoietin-producing hepatocellular receptor B2/erythropoietin-producing hepatocellular receptor-interacting B2/big mitogen-activated protein kinase 1(EphB2/EphrinB2/BMK1) signaling pathway to improve neural damage in vascular dementia rats. Methods Eighty SD male adult rats were randomly divided into a sham surgery group, a model group, a non acupoint electroacupuncture group, a nimodipine group, and an electroacupuncture three needle group. The vascular dementia rat model was made by the modified Pulsinelli four vessel occlusion method. After grouping, the rats in each group were subjected to water maze test, HE staining, Nissl staining, and transmission electron microscopy(TEM) to observe the pathological changes in the hippocampal CA1 area, and the expression of EphB2 and BMK1 in the hippocampal CA1 area was detected by immunohistochemistry; Detection of EphB2 and BMK1 protein expression in rat hippocampal CA1 region was detected by Western blotting. Results Compared with the model group, the escape latency of vascular dementia rats treated with electroacupuncture and nimodipine decreased (P<0.05), while the number of crossing platforms significantly increased (P<0.05); The result of HE staining, Nissl staining and TEM showed that compared with the model group, the neurons in hippocampal CA1 area of rats in the EA Zhisanzhen group and nimodipine group were arranged orderly, and the morphology and structure of cells and organelle were complete; Immunohistochemical method and Western blotting showed that the expression of EphB2 and BMK1 in the CA1 region of hippocampus in the model group was significantly lower than that in the sham surgery group (P<0.05); Compared with the model group, the expression of EphB2 and BMK1 in the hippocampal CA1 region of rats in the electroacupuncture Zhisanzhen group significantly increased (P<0.05), while the expression of EphB2 and BMK1 in the hippocampal CA1 region of rats in the non acupoint electroacupuncture group was not statistically significant (P>0.05). Compared with the nimodipine group, the expression of EphB2 and BMK1 in the hippocampal CA1 region of rats in the electroacupuncture Zhisanzhen group significantly increased (P<0.05). Conclusion Electroacupuncture may improve the damage of hippocampal neurons in vascular dementia rats by increasing the expression of EphB2 and BMK1 in the CA1 region of the hippocampus, thereby improving the learning and memory of vascular dementia rats.