BACKGROUND:The extracellular-regulated protein kinase 5(ERK5)signaling protein is essential for the survival of organisms,and resveratrol can promote osteoblast proliferation through various pathways.However,whether resveratrol can regulate osteoblast function through the ERK5 signaling protein needs further verification. OBJECTIVE:To explore the regulatory effect of ERK5 on the proliferation of MC3T3-E1 cells and related secreted proteins,and to further verify whether resveratrol can complete the above process by activating ERK5. METHODS:Mouse MC3T3-E1 preosteoblasts were treated with complete culture medium,XMD8-92(an ERK5 inhibitor),epidermal growth factor(an ERK5 activator),resveratrol alone,XMD8-92+EGF,and resveratrol+XMD8-92,respectively.Western blot assay was used to detect the expression of ERK5 and p-ERK5 proteins,proliferation-related proteins Cyclin D1,CDK4 and PCNA,and osteoblast-secreted proteins osteoprotegerin and receptor activator of nuclear factor-κB ligand in MC3T3-E1 cells of each group.The fluorescence intensity of ERK5,osteoprotegerin and receptor activator of nuclear factor-κB ligand in each group was detected by cell immunofluorescence staining,and cell proliferation was detected by EdU staining,respectively.The appropriate concentration and time of resveratrol intervention in MC3T3-E1 cells were determined by cell morphology observation and cell counting kit-8 assay. RESULTS AND CONCLUSION:The activation of ERK5 signaling protein could effectively promote the proliferation of MC3T3-E1 cells,up-regulate the osteoprotegerin/receptor activator of nuclear factor-κB ligand ratio.The appropriate concentration and time for resveratrol intervention in MC3T3-E1 cells was 5 μmol/L and 24 hours,respectively.Resveratrol could activate ERK5 signaling protein,thereby promoting osteoblast proliferation and up-regulating the osteoprotegerin/RANKL ratio.All these results indicate that resveratrol can promote the proliferation of MC3T3-E1 cells and up-regulate the osteoprotegerin/RANKL ratio by activating the ERK5 signaling protein.

ObjectiveTo study the effects of applying different microbial fertilizers on the growth and rhizosphere soil environment of Codonopsis pilosula and provide a theoretical basis for ecological cultivation of this medicinal plant. MethodsSeven groups were designed， including CK （no application of microbial fertilizer）， T1 （Trichoderma longibrachiatum fertilizer）， T2 （Bacillus subtilis fertilizer）， T3 （Trichoderma viride fertilizer）， T4 （compound microbial fertilizer）， T5 （C. pilosula stems and leaves fermented with compound microbial fertilizer）， and T6 （Scutellaria baicalensis stems and leaves fermented with T. viride fertilizer）. The physiological indicators， yield， and quality of C. pilosula and the physicochemical properties， enzyme activities， and microbial diversity in the rhizosphere soil of different fertilizer treatments were measured. ResultsGroup T1 showed slight decreases in soluble protein content （SPC） and superoxide dismutase （SOD）. Groups T2-T6 showed increases in physiological indicators such as proline （Pro）， soluble solids content （SSC）， SPC， catalase （CAT）， and peroxidase （POD） and a decrease in malondialdehyde （MDA） in C. pilosula leaves. All the fertilizer treatments increased the yield of C. pilosula and the total polysaccharide content in the roots. T1， T2， T3， T4， and T5 increased the total flavonoid content in the roots. Meanwhile， T4 increased the total saponin content in the roots. All the fertilizer treatments reduced the pH and increased the electric conductivity （EC）， soil organic matter （SOM）， and alkaline nitrogen （AN） in the soil. T2 and T5 increased the available phosphorus （AP）， and T3， T4， T5， and T6 increased the available potassium （AK） in the soil. All the fertilizer treatments increased the activities of urease， sucrase， and CAT in the soil. Except that T1 decreased the bacterial diversity in the soil， other fertilizer treatments significantly increased bacterial and fungal diversity in the soil. Different fertilizer treatments significantly affected the composition of bacterial and fungal communities in the soil. At the phylum level， the dominant bacterial phyla included Proteobacteria， Acidobacteriota， and Bacteroideta， and the dominant fungal phyla were Ascomycota， Mortierellomycota， and unclassified_fungi in the rhizosphere soil of C. pilosula after bacterial fertilizer treatment. At the genus level， unclassified Gemmatimonadaceae， Sphingomonas， and unclassified Vicinamibacteraceae were the dominant bacterial genera， while unidentified， unclassified Fungi， and unclassified Sordariomycetes were the dominant fungal genera in the rhizosphere soil. The results of redundancy analysis indicated that the main physicochemical factors affecting changes of microbial communities in the rhizosphere soil of C. pilosula were pH， EC， AK， AN， AP， and soil organic matter （SOM） in the soil. The correlation heatmap showed that Bryobacter had significantly positive correlations with EC， AK， and AN. There was a significantly negative correlation between Fusarium and SOM. In summary， applying an appropriate amount of microbial fertilizer can promote the growth and improve the rhizosphere soil environment of C. pilosula. ConclusionThe compound microbial fertilizer and the C. pilosula stems and leaves fermented with compound microbial fertilizer can improve the soil nutrients， growth， development， yield， and quality of C. pilosula， and thus they can be applied to the artificial cultivation of C. pilosula.

ObjectiveTo study the effects of applying different microbial fertilizers on the growth and rhizosphere soil environment of Codonopsis pilosula and provide a theoretical basis for ecological cultivation of this medicinal plant. MethodsSeven groups were designed， including CK （no application of microbial fertilizer）， T1 （Trichoderma longibrachiatum fertilizer）， T2 （Bacillus subtilis fertilizer）， T3 （Trichoderma viride fertilizer）， T4 （compound microbial fertilizer）， T5 （C. pilosula stems and leaves fermented with compound microbial fertilizer）， and T6 （Scutellaria baicalensis stems and leaves fermented with T. viride fertilizer）. The physiological indicators， yield， and quality of C. pilosula and the physicochemical properties， enzyme activities， and microbial diversity in the rhizosphere soil of different fertilizer treatments were measured. ResultsGroup T1 showed slight decreases in soluble protein content （SPC） and superoxide dismutase （SOD）. Groups T2-T6 showed increases in physiological indicators such as proline （Pro）， soluble solids content （SSC）， SPC， catalase （CAT）， and peroxidase （POD） and a decrease in malondialdehyde （MDA） in C. pilosula leaves. All the fertilizer treatments increased the yield of C. pilosula and the total polysaccharide content in the roots. T1， T2， T3， T4， and T5 increased the total flavonoid content in the roots. Meanwhile， T4 increased the total saponin content in the roots. All the fertilizer treatments reduced the pH and increased the electric conductivity （EC）， soil organic matter （SOM）， and alkaline nitrogen （AN） in the soil. T2 and T5 increased the available phosphorus （AP）， and T3， T4， T5， and T6 increased the available potassium （AK） in the soil. All the fertilizer treatments increased the activities of urease， sucrase， and CAT in the soil. Except that T1 decreased the bacterial diversity in the soil， other fertilizer treatments significantly increased bacterial and fungal diversity in the soil. Different fertilizer treatments significantly affected the composition of bacterial and fungal communities in the soil. At the phylum level， the dominant bacterial phyla included Proteobacteria， Acidobacteriota， and Bacteroideta， and the dominant fungal phyla were Ascomycota， Mortierellomycota， and unclassified_fungi in the rhizosphere soil of C. pilosula after bacterial fertilizer treatment. At the genus level， unclassified Gemmatimonadaceae， Sphingomonas， and unclassified Vicinamibacteraceae were the dominant bacterial genera， while unidentified， unclassified Fungi， and unclassified Sordariomycetes were the dominant fungal genera in the rhizosphere soil. The results of redundancy analysis indicated that the main physicochemical factors affecting changes of microbial communities in the rhizosphere soil of C. pilosula were pH， EC， AK， AN， AP， and soil organic matter （SOM） in the soil. The correlation heatmap showed that Bryobacter had significantly positive correlations with EC， AK， and AN. There was a significantly negative correlation between Fusarium and SOM. In summary， applying an appropriate amount of microbial fertilizer can promote the growth and improve the rhizosphere soil environment of C. pilosula. ConclusionThe compound microbial fertilizer and the C. pilosula stems and leaves fermented with compound microbial fertilizer can improve the soil nutrients， growth， development， yield， and quality of C. pilosula， and thus they can be applied to the artificial cultivation of C. pilosula.

Yinyang Gongji Pills have the effects of strengthening the body resistance to eliminate pathogenic factors, removing stasis, and reducing swelling, which is a commonly used traditional Chinese medicine(TCM) formula for treating intestinal accumulation. A real-world, registered, and single-arm clinical trial was conducted to observe the clinical efficacy and safety of Yinyang Gongji Pills combined with capecitabine in the treatment of advanced colorectal cancer and analyze the clinical characteristics of the patients. A total of 60 patients with advanced colorectal cancer who refused or could not tolerate standard treatment of western medicine were included in the study. They were treated with Yinyang Gongji Pills combined with capecitabine until disease progression or intolerable adverse events occurred. The main observation indicators were progression-free survival(PFS) and safety. The treatment effects of the patients under different baseline characteristics were analyzed. The clinical trial has found that the median PFS of all enrolled patients was 7.3 months, with 30.1% of patients having a PFS exceeding 12.0 months. Layered analysis showed that the median PFS of patients with the onset site being the colon and rectum were respectively 8.4 and 4.7 months. The median PFS of patients with high, medium, and low tumor burden were respectively 7.0, 4.7, and 10.8 months. The median PFS of patients with wild-type and mutant-type RAS/BRAF were respectively 7.9 and 6.9 months. The median PFS of patients with KPS scores ≥80 and ≤70 were respectively 7.9 and 6.5 months. The median PFS of patients treated with Yinyang Gongji Pills for ≥6, 3-6, and ≤3 months were respectively 8.0, 5.2, and 4.2 months. The median PFS of patients with spleen, kidney, liver, and lung syndrome differentiation in TCM were respectively 8.3, 6.7, 7.3, and 5.6 months. The median PFS of patients with TCM pathological factors including phlegm, dampness, and blood stasis were respectively 7.0, 7.3, and 6.5 months. Common adverse reactions include anemia, decreased white blood cells, decreased appetite, fatigue, and hand foot syndrome, with incidence rates being respectively 44.2%, 34.6%, 42.3%, 32.7%, and 17.3%. The results showed that the combination of Yinyang Gongji Pills and capecitabine demonstrated potential clinical efficacy and good safety in this study. The patients have clinical characteristics such as low tumor burden, onset site at the colon, KPS scores ≥ 80, long duration of oral TCM, and TCM syndrome differentiation including spleen or liver.
Humans ; Capecitabine/adverse effects* ; Colorectal Neoplasms/mortality* ; Drugs, Chinese Herbal/adverse effects* ; Male ; Middle Aged ; Female ; Aged ; Adult ; Treatment Outcome

eIF3a is a N ⁶-methyladenosine (m⁶A) reader that regulates mRNA translation by recognizing m⁶A modifications of these mRNAs. It has been suggested that eIF3a may play an important role in regulating translation initiation via m⁶A during infection when canonical cap-dependent initiation is inhibited. However, the death of animal model studies impedes our understanding of the functional significance of eIF3a in immunity and regulation in vivo. In this study, we investigated the in vivo function of eIF3a using eIF3a knockout and knockdown mouse models and found that eIF3a deficiency resulted in splenic tissue structural disruption and multi-organ damage, which contributed to severe sepsis induced by Lipopolysaccharide (LPS). Ectopic eIF3a overexpression in the eIF3a knockdown mice rescued mice from LPS-induced severe sepsis. We further showed that eIF3a maintains a functional and healthy immune system by regulating B cell function and quantity through m⁶A modification of mRNAs. These findings unveil a novel mechanism underlying sepsis, implicating the pivotal role of B cells in this complex disease process regulated by eIF3a. Furthermore, eIF3a may be used to develop a potential strategy for treating sepsis.

Objective To investigate the risk factors for postoperative pulmonary embolism in patients with spontaneous cerebral hemorrhage,and construct and verify the nomogram model.Methods A retrospective cohort study was conducted on 558 patients admitted in the First Affiliated Hospital of Chongqing Medical University and the Three Gorges Hospital Affiliated to Chongqing University.And 393 of them who hospitalized from January 2015 to January 2021 were assigned into a modeling group,and the other 165 patients from February 2021 to January 2023 into a validation group.Univariate and multivariate stepwise logistic regression analyses were used to screen out the risk factors associated with pulmonary embolism after spontaneous cerebral hemorrhage surgery.Then a nomogram model was build based on these factors and verified.Results Based on age,blood loss,Glasgow coma scale(GCS)score,surgical treatments,levels of fibrin degradation products,D-dimer and hemoglobin,plasma osmolality,and deep vein thrombosis,a risk model of pulmonary embolism was built.Receiver operating characteristic(ROC)curve analysis showed the model had good discriminability for the presence of pulmonary embolism,and the area under the curve(AUC)value was 0.908.Hosmer-Lemeshow goodness-fit test indicated that the model had a good fit to the verification set(Chi-square=14.805,df=8,P=0.063),the correction curve was close to the ideal curve,and the prediction probability of the model was close to the actual occurrence probability,suggesting the model having good accuracy.Decision curve analysis revealed that the established nomogram model can get benefits under a large range of threshold probabilities.Conclusion We develop a prediction model for postoperative pulmonary embolism in patients with spontaneous cerebral hemorrhage after surgical treatment,which shows good prediction performance in both the training and validation groups,and can be used for accurate,prompt and quick identification for the occurrence of pulmonary embolism in clinical practice.

Objective To observe the improvement of motor dysfunction and serum levels of C-reactive protein(CRP),blood glucose and blood lipid in post-stroke patients treated with scalp acupuncture at different needle retention time.Methods A total of 120 patients with motor dysfunction after stroke were randomly divided into control group,observation group 1 and observation group 2,with 40 cases in each group.The patients in the 3 groups were treated with scalp acupuncture,body acupuncture and routine rehabilitation exercise,once a day and 6 times a week,lasting for 2 weeks.The control group was given scalp acupuncture with retaining of needles for 30 minutes,the observation group 1 was given scalp acupuncture with retaining of needles for one hour,and the observation group 2 was given scalp acupuncture with retaining of needles for 2 hours.Before and after treatment,the 3 groups were observed in the changes of the scale scores of National Institutes of Health Stroke Scale(NIHSS),Fugl-Meyer Assessment(FM A),Berg Balance Scale(BBS)and modified Barthel Index(MBI),and the levels of laboratory indicators of peripheral blood CRP,fasting plasma glucose(FPG),total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C)and low-density lipoprotein cholesterol(LDL-C).After treatment,the clinical safety of the three groups was evaluated.Results(1)After treatment,the scale scores of NIHSS in the three groups were lower(P＜0.01)and the scale scores FMA,BBS and MBI were higher than those before treatment(P＜0.05 or P＜0.01).The comparison of post-treatment scale scores showed that the differences among the three groups were statistically significant(P＜0.01).The intergroup comparison showed that the decrease of NIHSS score and the increase of FMA,BBS and MBI scores in the observation group 2 were significantly superior to those in the control group and the observation group 1(P＜0.01);the improvement of FMA score in the observation group 1 was significantly superior to that in the control group(P＜0.01),while the improvement of NIHSS,BBS and MBI scores tended to be superior to that in the control group without statistically significant differences(P＞0.05).The results indicated that the curative effect of scalp acupuncture plus exercise regimen was positively correlated with the duration of needle retention for scalp acupuncture.(2)After treatment,the laboratory indicator levels of CRP and FPG in the peripheral blood of the three groups,the levels of TG and LDL-C in the two observation groups and the level of HDL-C in the observation group 2 were improved compared with those before treatment(P＜0.05 or P＜0.01).Statistically significant differences were presented in the post-treatment levels of CRP and TG in peripheral blood among the three groups(P＜0.05 or P＜0.01).The intergroup comparison showed that the improvement of CRP and TG levels in the observation group 2 was significantly superior to that in the control group,and the improvement of CRP level in the observation group 2 was significantly superior to that in the observation group 1,the differences being statistically significant(P＜0.05 or P＜0.01).The TC level in the three groups after treatment did not differ from that before treatment,and there was no significant difference in TC level after treatment among the three groups either(P＞0.05).(3)During the treatment,no adverse reactions such as fainting,needle breaking and hematoma occurred in the three groups,the vital signs of the patients were stable,and there were no obvious abnormal changes in pulse,blood pressure and respiratory rate.Conclusion Scalp acupuncture can effectively improve the motor function of post-stroke patients in a pasitive time-effect relationship with the needle retention,and better the curative effect can be achieved by retaining of the needle for 2 h.

Objective To understand the molecular characteristics of Streptomycin(SM)resistance in multidrug-resistant tuberculosis(MDR-TB)in Jiangxi Province,and to explore the relationship between SM resistant genes(rpsL,rrs and gidB)mutations and SM resistant phenotypes in Beijing genotype TB.Methods 106 non-replicated MDR-TB isolates were collected from Gaoxin Branch of The First Affiliated Hospital of Nanchang University and Jiangxi Provincial Chest Hospital from January to December 2021,and tested for drug-resistance phenotypes,whether they were Beijing genotype or not and the characteristics of rpsL,rrs and gidB gene mutations.Chi-square test was performed to determine whether rpsL,rrs and gidB mutations were related to genotypes and drug-resistance phenotypes.Results Among 106 cases of MDR-TB,76 cases were resistant to SM.A total of 58 cases had rpsL 43A>G mutation,8 cases had 88A>G mutation,5 cases had rrs mutation,and 3 cases had gidB mutation.Statistical analysis showed that the coincidence rate of gene mutation and phenotypic drug-resistance detection was 89.6%,and the specificity and sensitivity were 86.7%and 90.8%,respectively.The isolated rate of Beijing genotype TB was 88.7%,and the drug-resistant gene mutations were mainly concentrated in rpsL and rrs,while the drug-resistant mutations of non-Beijing genotype were mainly concentrated in gidB;in addition,Beijing genotype bacteria were more prone to gene mutations(P = 0.013),but there was no difference in phenotypic drug-resistance.Conclusions Mutations in rpsL,rrs,and gidB genes have a good coincidence rate with phenotypic drug-resistance,and molecular biology can be used to detect directly drug-resistance genes to predict bacterial resistance;TB genotypes are strongly associated with streptomycin resistance characteristics.

BACKGROUND:Fluid shear stress plays an important role in osteoblast proliferation and apoptosis.However,whether Caveolin-1 is involved in the process of fluid shear stress-induced proliferation and apoptosis in osteoblasts is unknown. OBJECTIVE:To explore the role of Caveolin-1 in fluid shear stress-regulated osteoblast proliferation and apoptosis. METHODS:The MC3T3-E1 osteoblasts in good growth status were selected and loaded with fluid shear stress at an intensity of 1.2 Pa for different times(0,30,60,90 minutes).The expression of Caveolin-1 protein was observed and conditions with a time of 60 minutes were screened for the experiment.MC3T3-E1 cells were divided into control group,fluid shear stress group,fluid shear stress+pcDNA 3.1 group(control),fluid shear stress+pcDNA Cav-1 group(plasmid overexpression),and intervened with fluid shear stress and overexpression of Cav-1,respectively.The expression of molecules related to proliferation and apoptosis in MC3T3-E1 cells was detected by qRT-PCR and western blot.In addition,the proliferative activity of MC3T3-E1 cells was detected by cell counting kit-8 and EdU assay;and cell apoptosis was detected by Hoechst 33258 and flow cytometry. RESULTS AND CONCLUSION:The expression of Caveolin-1 in MC3T3-E1 cells was significantly down-regulated after loading fluid shear stress,and the expression level was lowest after 60 minutes.Overexpression of Caveolin-1 attenuated the proliferation-promoting and apoptosis-suppressing effects of fluid shear stress in MC3T3-E1 cells.In conclusion,Caveolin-1 has a vital role in fluid shear stress-regulated osteoblast proliferation and apoptosis,which may offer a potential therapeutic strategy for osteoporosis.

This paper systematically combed and verified the name， origin， producing area， quality evaluation， harvesting， processing of Euryales Semen in famous classical formulas by consulting relevant ancient materia medica， medical books， prescription books and modern literature. The results showed that Euryales Semen was first collected by materia medica under the name of Jitoushi， and since the Ming dynasty， Qianshi has been used as a proper name and continues to this day， with other aliases such as Yanhuishi. Euryale ferox， a plant of the Nymphaeaceae family， is the same as that used in the past dynasties. However， due to long-term artificial domestication， the varieties vary with the origin， including Beiqian and Suqian. The medicinal part of Euryales Semen is mature seed kernel， its origin of ancient records mainly includes Shandong， Jiangsu， Henan and other places， since the Ming and Qing dynasties， Euryales Semen produced in Suzhou has been highly praised. Since modern times， it has gradually summarized and formed the best quality evaluation method of Euryales Semen with full grains， white cross-section， powdery enough and no broken powder. The harvesting time in the past dynasties was mainly August or in autumn. The main processing methods in the past dynasties included peeling for powder， pounding powder after steaming， drying and frying. Up to now， two mainstream processing methods of cleansing and stir-frying have been formed. Based on the research results， it is recommended that the mature seed kernel of E. ferox be used in famous classical formula Yihuangtang. Combined with the processing requirements of the original formula， it is suggested to refer to the stir-frying method in the general principles of processing of the current edition of Chinese Pharmacopoeia.