ObjectiveStudies have shown that nuciferine has anti-cerebral ischemia effect， but the specific mechanism of action has not been elaborated. Based on the transcriptome results， the pharmacological mechanism of nuciferine against cerebral ischemia was analyzed from multiple dimensions including tissue， cell， pathological process， biological process and signaling pathway. MethodsThirty SD rats were randomly divided into the sham group， model group and nuciferine group（40 mg·kg^-1） according to weight. Except for the sham group， the model of middle cerebral artery occlusion（MCAO） was established by thread embolization method after 30 min of administration in the other two groups. Twenty-four hours after surgery， transcriptome sequencing was used to detect the gene expression profiles in the cortex penumbra of rat cerebral tissue， and gene ontology（GO） and kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analysis were performed for differentially expressed genes. The mechanismof nuciferine against cerebral ischemia was analyzed from 5 dimensions of tissue， cell， pathological process， biological process and signaling pathway by the transcriptome-based multi-scale network pharmacology platform（TMNP）. ResultsTranscriptome sequencing and gene quantitative analysis showed that 667 genes were significantly reversed by nuciferine. Further enrichment analysis of KEGG and GO suggested that the pathways of nuciferine involved regulating stress response， ion transport， cell proliferation and differentiation， and synaptic function. TMNP research found that at the tissue level， nuciferine could significantly improve the cerebral tissue injury caused by ischemia. At the cellular and pathological levels， nuciferine could play an anti-cerebral ischemia role by improving the state of various nerve cells， mobilizing immune cells， regulating inflammation. And at the level of biological processes and signaling pathways， nuciferine mainly acted on the processes such as vascular remodeling， inflammation-related signaling pathways， and synaptic signaling. ConclusionCombined with the results of transcriptome sequencing， gene quantitative analysis and TMNP， the mechanism of nuciferine against cerebral ischemia may be related to processes such as intervening in stress response and inflammation， affecting vascular remodeling and regulating synaptic function. These results can provide a basis and reference for further study of the pharmacological mechanism of nuciferine against cerebral ischemia.

ObjectiveTo investigate the protective effects and mechanisms of Bushen Zhuyun prescription （BSZY） on abortion rats with kidney deficiency-corpus luteum inhibition syndrome. MethodsAn abortion rat model with kidney deficiency-corpus luteum inhibition syndrome was constructed. Pregnant mice aged 8-10 weeks were randomly divided into a control group （Control）， a model group （Model）， low-dose BSZY （BSZY-L）， medium-dose BSZY （BSZY-M）， and high-dose BSZY （BSZY-H） groups （2.57， 5.14， 10.28 g·kg^-¹）， and a Zishen Yutai Pill （ZSYT） group （1.575 g·kg^-¹）. Hematoxylin-eosin （HE） staining was used to evaluate histopathological changes in ovarian and decidual tissue of rats in each group. Enzyme-linked immunosorbent assay （ELISA） was employed to measure levels of estrogen （E₂）， progesterone （P）， luteinizing hormone （LH）， prolactin （PRL）， and follicle-stimulating hormone （FSH） in serum. The candidate targets of BSZY were obtained from the Traditional Chinese Medicine System Pharmacology Platform （TCMSP） and Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP） v2.0 databases， while disease targets for recurrent spontaneous abortion （RSA） were retrieved from GeneCards， DrugBank， Online Mendelian Inheritance in Man （OMIM）， and Therapeutic Target Database （TTD）. The intersection targets were identified by the Venny 2.1.0 platform. Pathway enrichment analysis was conducted based on the Metascape database to predict the potential mechanisms of BSZY. Additionally. Western blot was used to verify the effects of BSZY on the expression of estrogen receptor （ERα）， phosphatidylinositol 3-kinase （PI3K）， and protein kinase B （Akt） and explore its protective mechanism on RSA rats. ResultsCompared with the control group， the model group exhibited significantly decreased uterine， ovarian， and embryonic wet weights （P<0.05， P<0.01）， with an abortion rate of 57.18%. The ovarian tissue showed varying degrees of reduction in primordial follicles， primary follicles， mature follicles， and corpora lutea， along with a large number of atretic follicles. The endometrium was thinner， and decidual tissue exhibited cellular edema and disorganized arrangement. In contrast， compared with the model group， the BSZY groups at all doses and the ZSYT group demonstrated increased uterine， ovarian， and embryonic wet weights， along with a reduced abortion rate. The number of primordial follicles， primary follicles， mature follicles， and corpora lutea increased， while atretic follicles decreased. The endometrium thickened， and decidual tissue displayed normal cellular structure with tight arrangement. Additionally， the model group showed significantly decreased levels of E₂， P， PRL， and FSH in serum （P<0.05， P<0.01）， along with a decreasing trend in LH level. In contrast， the BSZY groups at all doses exhibited significantly elevated levels of E₂， P， LH， PRL， and FSH in serum （P<0.05， P<0.01）. Network pharmacology predictions suggested that BSZY may exert protective effects against abortion in rats by activating the ERα/PI3K/Akt signaling pathway. Western blot results confirmed that BSZY significantly upregulated the expression of ERα， PI3K， and p-Akt proteins （P<0.05， P<0.01）. ConclusionBSZY has a protective effect on the abortion rats with kidney deficiency-corpus luteum inhibition syndrome， possibly by activating the ERα/PI3K/Akt signaling pathway to reduce ovarian apoptosis and regulate endocrine function， thereby lowering the abortion rate.

With the growing emphasis on maternal and child oral health, the significance of managing oral health across preconception, pregnancy, and infancy stages has become increasingly apparent. Oral health challenges extend beyond affecting maternal well-being, exerting profound influences on fetal and neonatal oral development as well as immune system maturation. This expert consensus paper, developed using a modified Delphi method, reviews current research and provides recommendations on maternal and child oral health management. It underscores the critical role of comprehensive oral assessments prior to conception, diligent oral health management throughout pregnancy, and meticulous oral hygiene practices during infancy. Effective strategies should be seamlessly integrated across the life course, encompassing preconception oral assessments, systematic dental care during pregnancy, and routine infant oral hygiene. Collaborative efforts among pediatric dentists, maternal and child health workers, and obstetricians are crucial to improving outcomes and fostering clinical research, contributing to evidence-based health management strategies.
Humans ; Pregnancy ; Female ; Infant ; Consensus ; Mouth Diseases/therapy* ; Pregnancy Complications/therapy* ; Oral Health ; Infant, Newborn ; Delphi Technique ; Oral Hygiene

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Aim To explore the role of the ten-eleven translocation 2(TET2)/ubiquinol-cytochrome C reductase hinge protein(UQCRH)axis in the inhibition of vascular smooth muscle cell(VSMC)apoptosis by fibroblast growth fac-tor-2(FGF-2).Methods Cultured VSMCs were divided into control group,FGF-2 group,and FGF-2+fibroblast growth factor receptor(FGFR)pan-inhibitor LY2874455 group.VSMCs overexpressing TET2(OETET2)or UQCRH(OEUQCRH)were divided into control group,FGF-2 group,and OETET2+FGF-2 or OEUQCRH+FGF-2 group.Ho-echst33342 and PI staining were used to detect cell apoptosis,CCK-8 assay was employed to measure cell proliferation,and Western blot was used to examine the expression levels of apoptosis-related proteins pro-Caspase-3,cleaved Caspase-3,Bax,Bcl-2,as well as TET2 and UQCRH.The NCBI and methprimer websites were utilized for predicting and analyzing CpG island sites in the UQCRH gene promoter.Results FGF-2 could inhibit VSMC apoptosis,promote proliferation,downregulate apoptosis-related proteins cleaved Caspase-3,Bax,TET2,and UQCRH expression,and upregulate anti-ap-optotic protein Bcl-2 expression(compared with control group,P＜0.05).However,it did not affect pro-Caspase-3 ex-pression(compared with control group,P＞0.05).LY2874455 could counteract the effects of FGF-2(compared with FGF-2 group,P＜0.05).Overexpression of TET2 or UQCRH could reverse the anti-apoptotic and pro-proliferative effects of FGF-2 on VSMC,with upregulation of apoptosis-related protein expression and downregulation of anti-apoptotic protein expression(compared with FGF-2 group,P＜0.05).The UQCRH gene promoter region contained three CpG islands.Overexpression of TET2 could upregulate UQCRH expression in VSMC treated with FGF-2(compared with FGF-2 group,P＜0.05).Conclusion FGF-2,by inhibiting TET2 expression and UQCRH expression,reduces VSMC apoptosis and promotes its proliferation.

Objective To establish an analytical method combining gas chromatography-tandem mass spectrometry(GC-MS)and liquid chromatography-tandem mass spectrometry(LC-MS)to detect diazepam residue in bait nest materials and fish samples,and improve the pretreatment steps of samples to make the experimental results accurate and the sample processing convenient and fast.Methods Taking diazepam as the research object,samples were extracted with methanol and dichloromethane/n-hexane as solvents according to the type,and the supernatant was taken for detection after centrifugation.Results The diazepam standard sample showed a good linear relationship in the range of 10～10 000 ng/mL.The retention times in methanol and mixed solvent were 13.54 min and 13.83 min,respectively,and the correlation coefficients were 0.998 and 0.999,respectively;The limit of detection(LOD)of using methanol as extraction solvent was 2 ppb,and limit of quantification(LOQ)was 6 ppb.The LOD of using mixed solvents was 5 ppb,and the LOQ was 15 ppb.When the sample is a bait nest material,the GC-MS spectrum was clear and standard,and the peak shape was sharp and prominent;When the sample is biological specimen,the GC-MS spectra are disturbed by matrix,while the LC-MS data is more accurate and faster.Conclusion It is more appropriate to use GC-MS to determine the content of bait nest materialsamples,and it is more accurate to LC-MS to determine the content of fish samples due to the complexity of the organism.

Background and purpose:For patients with human epidermal growth factor receptor 2(HER2)-positive metastatic breast cancer,trastuzumab treatment can prolong the overall survival and significantly improve the prognosis of patients.However,the reference original research trastuzumab(Herceptin?)is more expensive.Biosimilars have comparable efficacy and safety profiles while increasing patient access to treatment.This clinical trial aimed to evaluate the efficacy,pharmacokinetics,safety and immunogenicity of the trastuzumab biosimilar AK-HER2 compared to trastuzumab(Herceptin?)in patients with HER2-positive metastatic breast cancer.Methods:This multi-center,randomised,double-blind phase Ⅲ clinical trial was conducted in 43 subcenters in China.This study complied with the research protocol,the ethical principles stated in the Declaration of Helsinki and the quality management standards for drug clinical trials.It was approved by the hospital's medical ethics committee.The clinical trial registration agency is the State Food and Drug Administration(clinical trial approval number:2015L04224;clinical trial registration number:CTR20170516).Written informed consent was obtained from subjects before enrollment.Enrolled patients were randomly assigned to the AK-HER2 group and the control group,respectively receiving AK-HER2 or trastuzumab(initial loading dose 8 mg/kg,maintenance dose 6 mg/kg,every 3 weeks as a treatment cycle,total treatment time is 16 cycles)in combination with docetaxel(75 mg/m2,treatment duration is at least 9 cycles).The primary endpoint of this clinical trial was the objective response rate(ORR9)between the AK-HER2 group and the control group in the 9th cycle.Secondary efficacy endpoints included ORR16,disease control rate(DCR),clinical benefit rate(CBR),progression-free survival(PFS)and 1-year survival rate.In this study,100 subjects(AK-HER2 group to control group=1:1)were randomly selected for blood sample collection after the 6th cycle of medication,The collection time points were 45 minutes after infusion(the end of administration),4,8,24,72,120,168,336,and 504 hours after the end of administration.After collection,blood samples were analyzed by PK parameter set(PKPS).Other evaluation parameters included safety and immunogenicity assessment.Results:A total of 550 patients with HER2-positive metastatic breast cancer were enrolled in this clinical trial between Sep.2017 and Mar.2021.In the AK-HER2 group(n=237),129 subjects in the experimental group achieved complete response(CR)or partial response(PR),and the ORR9 was 54.4%.There were 134 subjects in the control group(n=241)who achieved CR or PR,and the ORR9 was 55.6%.The ORR9 ratio between the AK-HER2 group and the control group was 97.9%[90%confidence interval(CI):85.4%-112.2%,P=0.784],which was not statistically significant.In all secondary efficacy endpoints,no statistically significant differences were observed between the two groups.We conducted a mean ratio analysis of pharmacokinetics(PK)parameters between the AK-HER2 group and the control group,and the results suggested that the pharmacokinetic characteristics of the two drugs are similar.The incidence of treatment emergent adverse event(TEAE)leading to drug reduction or suspension during trastuzumab treatment was 3.6%(10 cases)in the AK-HER2 group and 8.1%(22 cases)in the control group.There was statistically significant difference between the two groups(P=0.027).The incidence rate was significantly lower in the AK-HER2 group than in the control group,and there was no statistically significant difference among the other groups.The differences in the positive rates of anti-drug antibodies(ADA)and neutralizing antibodies(NAB)between groups were of no statistical significance(P=0.385 and P=0.752).Conclusion:In patients with HER2-positive metastatic breast cancer,AK-HER2 was comparable to the trastuzumab(Herceptin?)in terms of drug efficacy,pharmacokinetics,safety and immunogenicity.

Objective:To investigate the effect of five-element music therapy combined with meridian-based acupoint massage timed according to qi circulationon on negative emotions and sleep quality in older adults with chronic heart failure. Methods:A total of 112 older adult patients with chronic heart failure who received treatment at The Affiliated Hospital of Hangzhou Normal University between January 2022 and June 2023 were included in this study. They were randomly divided into a control group ( n = 56) and a study group ( n = 56) using the random number table method. Based on conventional treatment, the control group received five-element music therapy, while the intervention group underwent a combination of five-element music therapy and meridian-based acupoint massage timed according to qi circulation. Before and after the intervention, a comparison was made between the two groups in terms of the scores of the Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), Pittsburgh Sleep Quality Index (PSQI), and various dimensions of the Minnesota Living with Heart Failure Questionnaire (MLHFQ). Additionally, the sleep outcome and patient satisfaction were also compared between the two groups. Results:After intervention, the scores of the HAMA and HAMD in the study group were (11.29 ± 2.48) points and (12.48 ± 3.36) points, respectively. In contrast, the control group had scores of (15.93 ± 3.35) points and (16.50 ± 4.32) points, respectively. After intervention, the scores of the HAMA and HAMD scales in both the study and control groups demonstrated a significant reduction in comparison with their respective pre-intervention scores [study group: (20.13 ± 5.18) points, (23.95 ± 8.97) points, control group: (19.36 ± 5.45) points, (23.79 ± 7.61) points, t = 15.35, 10.24, 5.65, 8.93, all P < 0.001). After intervention, the scores of the HAMA and HAMD scales in the study group were significantly lower than those in the control group ( t = -8.34, -5.49, both P < 0.001). After intervention, the scores of the PSQI in the study and control groups were (7.05 ± 0.96) points and (9.91 ± 1.28) points, respectively. After intervention, the scores of PSQI in both the study and control groups demonstrated a significant reduction compared with their respective pre-intervention scores [study group: (12.98 ± 2.21) points, control group: (12.50 ± 2.48) points, t = 24.68, 9.79, both P < 0.05]. After intervention, the score of the PSQI in the study group was significantly lower than that in the control group ( t = 13.34, P < 0.05). Based on the scores across various dimensions of the MLHFQ, it was observed that after intervention, the scores of emotional, physical, and other domains in both the study and control groups [study group: (9.36 ± 2.29) points, (16.95 ± 3.80) points, (18.50 ± 2.33) points; control group: (12.93 ± 2.00) points, (19.98 ± 3.98) points, (20.04 ± 2.24) points] decreased significantly compared with their pre-intervention scores [study group: (15.57 ± 1.55) points, (26.23 ± 4.63) points, (21.18 ± 2.50) points, control group: (16.09 ± 1.87) points, (25.32 ± 4.40) points, (21.57 ± 2.69) points, t = 21.66, 18.55, 8.44, 11.29, 11.73, 4.61, all P < 0.001]. After intervention, the scores of emotional, physical, and other domains in the study group were significantly lower than those in the control group ( t = -8.79, -4.13, -3.56, all P < 0.05). Patient satisfaction in the study group was superior to that that in the control group [98.21% (55/56) vs. 87.50% (49/56), χ2 = -3.09, P < 0.05]. Total effective rate of intervention on sleep in the study group was significantly higher than that in the control group [92.86% (52/56) vs. 78.57% (44/56), χ2 = -2.09, P < 0.05]. Conclusion:Five-element music therapy combined with meridian-based acupoint massage timed according to qi circulationon in the treatment of chronic heart failure in older adults can effectively alleviate negative emotions, improve the quality of life and sleep, and increase patient satisfaction with nursing care.

BACKGROUND:Hydroxyapatite is the main inorganic component of bone tissue.The polymer has the structure and function of a biomimetic extracellular matrix.The composites of hydroxyapatite and polymer have been widely studied. OBJECTIVE:To summarize the research status of hydroxyapatite composite polymer materials for bone tissue repair. METHODS:The articles collected in PubMed,Web of Science,CNKI and WanFang databases were searched from January 2010 to April 2023.The Chinese and English search terms were"hydroxyapatite,polymer,composites,degradability,bone defect,bone repair".Finally,75 articles were included for review. RESULTS AND CONCLUSION:Polymers often used in composite with hydroxyapatite for bone tissue repair include natural polymers(collagen,chitosan,alginate,serine protein,cellulose,hyaluronic acid,and polyhydroxybutyrate)and synthetic polymers[polylactic acid,polylactic acid-hydroxyacetic acid copolymer,poly(has-lactide),poly(amino acid)and poly(vinyl alcohol)].The mechanical properties and osteoinductivity of hydroxyapatite/polymer composites were improved compared with pure hydroxyapatite.Hydroxyapatite composite with polymers can be made into porous scaffolds,hydrogels,and coatings for bone repair.Hydroxyapatite/polymer composites can accelerate bone reconstruction with a slow release of loaded drugs and cytokines due to their bionic extracellular matrix structure and function.Based on the diversity of causes of bone defects and the fact that bone repair is a complex continuous process involving multiple biological factors and proteins,repair materials with mechanical properties matching bone tissue,degradation processes synchronized with bone repair,and efficient osteogenesis and vascularization need to be further investigated.

BACKGROUND:As a leading technique in the treatment of primary stenosis by posterior spinal endoscopy through unilateral approach and bilateral decompression using single channel endoscopy,the long-term efficacy needs to be further observed.There are few reports on the scope of intraoperative resection and few relevant studies on biomechanics and finite element analysis. OBJECTIVE:A three-dimensional finite element model was established to evaluate the effects of bilateral lumbar canal decompression under a one-hole split endoscope on lumbar range of motion and intradiscal pressure,to provide suggestions for clinical operation and theoretical basis for further clinical research. METHODS:A complete L3-L5 vertebral body model was reconstructed by CT images of nine healthy volunteers,which was used as the preoperative model M1.The simulated surgical resection range of L4-L5 was performed,and 1/4,1/3 and 1/2 of bilateral facet joints were removed respectively to obtain models M2,M3 and M4.The range of motion and the maximum Von Mises stress of the four models were compared in the six directions of forward bending,backward extension,left and right bending,and left and right rotation. RESULTS AND CONCLUSION:(1)The L3-L5 finite element model established in this study was effective,and the range of motion was within the range of previous solid studies under six motion states.(2)Compared with the M1 model,the L4-L5 lumbar spine range of motion increased with the increase of resection range in M2 with M3 and M4 models under forward bending,left and right bending and left and right rotation loading,and the difference was significant(P＜0.05).Under posterior extension loading,there was no significant difference in lumbar range of motion between M1 and M2(P＞0.05),but there was a significant difference of M1,M3 and M4(P＜0.05).(3)The range of motion of the L3-L4 lumbar spine had no significant change with the increase of bilateral facet arthrotomy(P＞0.05).(4)There was a significant difference in the maximum value of L4-L5 Von Mises between M1 and M2(P＜0.05),and there was a significant difference in the maximum value of L4-L5 Von Mises between M1 and M3,M4(P＜0.01),and the maximum value of L4-L5 lumbar von Mises increased with the increasing range of bilateral facet joint resection.Resection of more than 1/3 was particularly obvious.(5)The maximum value of Von Mises in the L3-L4 lumbar spine was increased with the increase of the resection range under forward bending,left and right bending and left and right rotation loading and the difference was significant(P＜0.05).(6)The results exhibited that the L4-L5 lumbar motion and intervertebral disc pressure increased with the increase of the excision range.Intervertebral disc pressure at L3-L4 increased with the increased extent of excision,but the lumbar range of motion was not significantly affected.In conclusion,the stability of the operative segment may be affected by the increase in the scope of facet joint resection.Although the immediate stability of adjacent segments is not affected,it may accelerate disc degeneration.