BACKGROUND:Studies have reported that alendronate intake significantly increases bone mineral density in patients with osteoporosis. OBJECTIVE:To analyze and compare the changes in metabolites before and after alendronate intervention in ovariectomized rats by chromatography-mass spectrometry,and to further explore the specific mechanism and target of alendronate in the treatment of osteoporosis. METHODS:A total of 36 female Sprague-Dawley rats were randomly divided into model group,alendronate sodium group and sham operation group.The osteoporosis model was established by ovariectomy in the first two groups.Four weeks after modeling,the rats in the alendronate group were intragastrically given alendronate sodium,while those in the sham operation group and model group were given equal volume of normal saline.After 12 weeks of continuous gavage,the metabolites of the lumbar spine were analyzed by chromatography-mass spectrometry,and the common differential metabolites were obtained,which were analyzed by bioinformatics such as Kyoto Gene and Genome Encyclopedia pathway. RESULTS AND CONCLUSION:Totally 17 different metabolites were obtained in the three groups.The enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes showed that alendronate sodium could regulate unsaturated fatty acid biosynthesis,linoleic acid metabolism and other pathways to protect ovariectomized rats.These results indicate that alendronate sodium may exert its anti-osteoporosis effect by interfering with unsaturated fatty acid bioanabolism and linoleic acid metabolism,so as to achieve the purpose of preventing osteoporosis

Objective To evaluate the efficacy and safety of Qixian Tongluo Formula in the treatment of post-cerebral infarction paralysis with kidney deficiency and blood stasis syndrome,and to preliminarily explore the molecular mechanism of Qixian Tongluo Formula in improving impaired motor function from the perspective of cross-kingdom regulation of Chinese medicine microRNA(miRNA).Methods A pragmatic randomized controlled trial was conducted with 102 patients in the recovery period of post-cerebral infarction paralysis with kidney deficiency and blood stasis syndrome in our hospital.Patients were randomly divided into trial group and control group,with 51 cases in each group.The control group received standard Western medicine standard treatment,while the trial group received Qixian Tongluo Formula in addition to the standard treatment,with one dose per day,boiled in water,and taken warm after breakfast and dinner for a course of 2 months.The disability rate was used as the main efficacy indicator,and the incidence of adverse reactions was used as a safety indicator.miRNA from patient serum and Qixian Tongluo decoction were extracted respectively,and high-throughput sequencing was performed.The two sequences were compared to screen out the cross-kingdom gene transfer of Chinese medicine miRNA.Finally,its target genes of miRNA were predicted,and GO function and KEGG pathway enrichment analysis were carried out.Results A total of 67 patients completed the clinical trial,including 36 cases in the trial group and 31 cases in the control group;The disability rate in the trial group(13.9%)was lower than that in the control group(35.5%)(P<0.05);The incidence of adverse reactions was similar between the trial group(7.69%)and the control group(6.06%)(P>0.05);A total of 9530 Qixian Tongluo decoction miRNA sequences were screened,with 150 potentially involved in cross-kingdom gene transfer,including families such as miR-15 and miR-17;According to the target gene prediction of the top 10 miRNAs in cross-kingdom gene transfer of Chinese medicine,345 overlapping target genes were obtained;GO functional enrichment analysis revealed 16 biological processes,7 cellular components,and 2 molecular functions among the top 25 enriched functions,while KEGG pathway analysis mainly focused on the transforming growth factor-βsignaling pathway,neurotrophin signaling pathway,which are closely related to neural repair and functional recovery processes such as glial scar formation and synaptic plasticity after cerebral ischemia.Conclusion Qixian Tongluo Formula can significantly improve the functional independence level of patients with kidney deficiency and blood stasis syndrome in the recovery period of paralysis after cerebral infarction,offering a safe and effective treatment option for these patients;There were a large number of miRNAs in Qixian Tongluo decoction,some of which could cross-kingdom transferred into the human blood circulation,and promote the recovery of motor function in patients with cerebral infarction through multi-target,multi link and multi pathway gene network regulation.This study provides a new idea for subsequent clinical and basic research.

The objective of this study was to develop a rapid and precise detection technique for por-cine Senecavirus A(SVA)employing reverse transcription recombinase polymerase amplification(RT-RAA)in conjunction with CRISPR Cas13a technology.Additionally,the study aimed to opti-mize the assay's reaction conditions to enhance amplification efficiency.Eight RT-RAA primer sets were designed based on the conserved gene sequence of porcine SVA,and a series of reaction condi-tions were evaluated to refine the RT-RAA reaction system.Subsequently,CRISPR-derived RNA(crRNA)sequences were developed and selected to construct the RT-RAA-CRISPR reaction sys-tem.The method's specificity was determined by examining six prevalent porcine pathogenic nucleic acids,while its sensitivity was assessed using SVA cRNA standards quantified by digital PCR.The method's stability and the consistency of clinical sample analysis were also evaluated.The findings revealed that the optimized RT-RAA and CRISPR reaction systems exhibited the highest amplifi-cation efficiency at a reaction temperature of 37 ℃.Among the eight crRNAs,five were identified as exhibiting the strongest detection signals.The formulated RT-RAA-CRISPR Cas13a method demonstrated exceptional specificity,showing no cross-reactivity with other common porcine disea-ses,including ASFV,PRRSV,PEDV,PCV2,CSFV,and PRV.The method achieved high sensitivi-ty,detecting as low as 0.86 copies/μL of SVA,and exhibited stable fluorescence output,robust re-producibility,and the ability to complete clinical sample analysis within 50 minutes.Consistency e-valuation with six positive and 58 negative samples indicated 100％agreement in outcomes.These results substantiate that the study successfully established a rapid and specific RT-RAA-CRISPR Cas13a detection method for the on-site identification of porcine Senecavirus A,demonstrating high specificity and sensitivity,and holds promise for application in SVA monitoring and control initia-tives.

Objective To evaluate the efficacy and safety of Qixian Tongluo Formula in the treatment of post-cerebral infarction paralysis with kidney deficiency and blood stasis syndrome,and to preliminarily explore the molecular mechanism of Qixian Tongluo Formula in improving impaired motor function from the perspective of cross-kingdom regulation of Chinese medicine microRNA(miRNA).Methods A pragmatic randomized controlled trial was conducted with 102 patients in the recovery period of post-cerebral infarction paralysis with kidney deficiency and blood stasis syndrome in our hospital.Patients were randomly divided into trial group and control group,with 51 cases in each group.The control group received standard Western medicine standard treatment,while the trial group received Qixian Tongluo Formula in addition to the standard treatment,with one dose per day,boiled in water,and taken warm after breakfast and dinner for a course of 2 months.The disability rate was used as the main efficacy indicator,and the incidence of adverse reactions was used as a safety indicator.miRNA from patient serum and Qixian Tongluo decoction were extracted respectively,and high-throughput sequencing was performed.The two sequences were compared to screen out the cross-kingdom gene transfer of Chinese medicine miRNA.Finally,its target genes of miRNA were predicted,and GO function and KEGG pathway enrichment analysis were carried out.Results A total of 67 patients completed the clinical trial,including 36 cases in the trial group and 31 cases in the control group;The disability rate in the trial group(13.9%)was lower than that in the control group(35.5%)(P<0.05);The incidence of adverse reactions was similar between the trial group(7.69%)and the control group(6.06%)(P>0.05);A total of 9530 Qixian Tongluo decoction miRNA sequences were screened,with 150 potentially involved in cross-kingdom gene transfer,including families such as miR-15 and miR-17;According to the target gene prediction of the top 10 miRNAs in cross-kingdom gene transfer of Chinese medicine,345 overlapping target genes were obtained;GO functional enrichment analysis revealed 16 biological processes,7 cellular components,and 2 molecular functions among the top 25 enriched functions,while KEGG pathway analysis mainly focused on the transforming growth factor-βsignaling pathway,neurotrophin signaling pathway,which are closely related to neural repair and functional recovery processes such as glial scar formation and synaptic plasticity after cerebral ischemia.Conclusion Qixian Tongluo Formula can significantly improve the functional independence level of patients with kidney deficiency and blood stasis syndrome in the recovery period of paralysis after cerebral infarction,offering a safe and effective treatment option for these patients;There were a large number of miRNAs in Qixian Tongluo decoction,some of which could cross-kingdom transferred into the human blood circulation,and promote the recovery of motor function in patients with cerebral infarction through multi-target,multi link and multi pathway gene network regulation.This study provides a new idea for subsequent clinical and basic research.

The objective of this study was to develop a rapid and precise detection technique for por-cine Senecavirus A(SVA)employing reverse transcription recombinase polymerase amplification(RT-RAA)in conjunction with CRISPR Cas13a technology.Additionally,the study aimed to opti-mize the assay's reaction conditions to enhance amplification efficiency.Eight RT-RAA primer sets were designed based on the conserved gene sequence of porcine SVA,and a series of reaction condi-tions were evaluated to refine the RT-RAA reaction system.Subsequently,CRISPR-derived RNA(crRNA)sequences were developed and selected to construct the RT-RAA-CRISPR reaction sys-tem.The method's specificity was determined by examining six prevalent porcine pathogenic nucleic acids,while its sensitivity was assessed using SVA cRNA standards quantified by digital PCR.The method's stability and the consistency of clinical sample analysis were also evaluated.The findings revealed that the optimized RT-RAA and CRISPR reaction systems exhibited the highest amplifi-cation efficiency at a reaction temperature of 37 ℃.Among the eight crRNAs,five were identified as exhibiting the strongest detection signals.The formulated RT-RAA-CRISPR Cas13a method demonstrated exceptional specificity,showing no cross-reactivity with other common porcine disea-ses,including ASFV,PRRSV,PEDV,PCV2,CSFV,and PRV.The method achieved high sensitivi-ty,detecting as low as 0.86 copies/μL of SVA,and exhibited stable fluorescence output,robust re-producibility,and the ability to complete clinical sample analysis within 50 minutes.Consistency e-valuation with six positive and 58 negative samples indicated 100％agreement in outcomes.These results substantiate that the study successfully established a rapid and specific RT-RAA-CRISPR Cas13a detection method for the on-site identification of porcine Senecavirus A,demonstrating high specificity and sensitivity,and holds promise for application in SVA monitoring and control initia-tives.

Objective To observe the effect of Qixian Tongluo Formula on contralateral corticospinal tract(CST)remodeling and motor functional recovery in rats with cerebral infarction,and to explore its potential molecular mechanism from the perspective of regulating factors related to never remodeling.Methods The rat middle cerebral artery occlusion(MCAO)model was established by silk thread ligation.Fifty model rats were randomly divided into model group,citicoline group(0.054 g·kg-1),Qixian Tongluo Formula low-,medium-and high-dose(7.83,15.66,31.32 g·kg-1)groups,and sham operation group,with 10 rats in each group.The intervention administration was started on the 3rd day after operation once a day for 26 consecutive days.On the 3rd,14th and 28th day after operation,the gross motor function was evaluated by Longa score,and the fine motor function was evaluated by beam-walking test(BWT)score.The contralateral motor cortex was injected with the nerve tracer biotin dextran amine(BDA)on the 14 th day after operation to anterogradely trace the CST.On the 28th day after operation,the expression of axonal growth associated protein-43(GAP-43)and BDA positive fibers in the contralateral motor cortex and cervical spinal cord were detected by immunohistochemistry.The co-localization areas of BDA positive fibers and presynaptic marker protein vesicular glutamate transporter 1(VGLUT1)in the cervical spinal cord gray matter were detected by immunofluorescence.The expressions of brain-derived neurotrophic factor(BDNF),glial cell-derived neurotrophic factor(GDNF),nerve growth factor(NGF)and nerve remodeling-associated inhibitory factor[Nogo-A,oligodendrocyte myelin glycoprotein(OMgp)and myelin-associated glycoprotein(MAG)]in the contralateral motor cortex were detected by Western Blot.Pearson correlation analysis was used to analyze the correlation between Longa score or BWT score and BDA/VGLUT1 co-localization area,respectively.Results Compared with the sham operation group,rats in the model group had obvious symptoms of motor function deficits,and the Longa scores were significantly increased(P＜0.01)and the BWT scores were significantly decreased(P＜0.05,P＜0.01)at each time point.The expression of GAP-43 in the contralateral motor cortex and cervical spinal cord was up-regulated(P＜0.05),the number of edge-crossing fibers from the posterior funiculus in cervical cord was increased(P＜0.05),the co-localization area of BDA/VGLUT1 in the gray matter of the cervical spinal cord was increased(P＜0.05),the expressions of BDNF,GDNF and NGF in the contralateral motor cortex were up-regulated(P＜0.05),while the expressions of Nogo-A,OMgp and MAG were down-regulated(P＜0.05).Compared with the model group,the Longa scores in each administration group on the 14th and 28th day after MCAO operation were significantly decreased(P＜0.01),the BWT scores were significantly increased(P＜0.01),the expression of GAP-43 in the contralateral motor cortex and cervical spinal cord was significantly up-regulated(P＜0.01).The number of edge-crossing fibers from the posterior funiculus in cervical cord was significantly increased(P＜0.01),the co-localization area of BDA/VGLUT1 in the gray matter of the cervical spinal cord was significantly increased(P＜0.01).The expressions of BDNF,GDNF and NGF in the contralateral motor cortex were significantly up-regulated(P＜0.01,P＜0.05),while the expressions of Nogo-A,OMgp and MAG were significantly down-regulated(P＜0.05),and the most significant effect was observed in the high dose group.The Longa score was negatively correlated with the co-localization area of BDA/VGLUT1(r=-0.89,P＜0.01),and the BWT score was positively correlated with the co-localization area of BDA/VGLUT1(r=0.84,P＜0.01).Conclusion Qixian Tongluo Formula can improve motor function through promoting contralateral CST remodeling in MCAO rats after cerebral infarction,and the molecular mechanism may be related to the regulation of the expression of nerve remodeling-associated factor in the contralateral motor cortex.

The construction of "New Medicine" is the leader of the innovative development of medical education in China in the new era. Strengthening the cross-integration of medicine and science is helpful to promote the training of top-notch interdisciplinary innovative talents under the multidisciplinary background of "Medicine + X". The applied psychology major in medical colleges has unique advantages in education and teaching resources. How to combine the advantages to construct the education model of the integration of medicine and science is still in the exploration stage. This paper analyzes the current situation of talent training of the applied psychology major in medical colleges and the new requirements for discipline-major construction under the background of "New Medicine" construction, demonstrates the measures to strengthen the deep integration of medicine and science from the aspects of curriculum system setting, teacher team construction, practice teaching, and teaching method reform, and puts forward the innovative education model of the integration of medicine and science in applied psychology-medicine interdisciplinary training.

Chronic myeloid leukemia(CML)is a hematological system malignant tumor characterized by the appearance of Ph chromosomes and the formation of BCR-ABL fusion gene.With the emergence of tyrosine kinase inhibitors,the efficacy and survival of CML have been improved significantly.However,there are still some patients with inevitable disease progression and recurrence.In CML patients,the body's own an-ti-tumor immunity can play a role in monitoring,recognizing and eliminating the leukemia cells,which is closely correlated with the occurrence,development,curative efficacy and prognosis of the disease.The immune cells such as natural killer(NK)cells,T cells,dendritic cells,Treg and MDSC play a key role in anti-tumor immunity.Therefore,this article reviews the characteristics of CML immune cells,correlation between the body's own anti-tumor immune status and therapeutic effect,and the recent progress of CML immunotherapy.

Objective This research assessed the impact of incorporating choledochoscopy with laparoscopic left hepatectomy on stress response and bile duct stone removal in patients presenting with complex intrahepatic biliary stones.Methods Clinical data of 194 patients with complex intrahepatic biliary stones from June 2020 to June 2024 were retrospectively analyzed.The patients were divided into control group (n=97) and observation group (n=97) according to different operation methods.The control group received laparoscopic left hepatectomy,while the observation group received choledochoscopic lithotomy combined with laparoscopic left hepatectomy.The changes of stress indexes[cortisol (Cor),adrenaline (AD)],inflammatory factors[C-reactive protein (CRP),interleukin-6 (IL-6),tumor necrosis factor-α (TNF-α)]in the two groups before and 3 days after operation were compared.The liver function indexes[alanine transaminase (ALT),total bilirubin (TBiL),glutamyl transferase (GGT)]of the two groups before and 7 days after operation were compared.The treatment effect levels of the two groups were evaluated 3 months after operation.The incidence of postoperative complications (bile leakage,infection,residual stones and pleural effusion) was recorded and compared between the two groups.Results Three days before and after operation,the levels of Cor,AD,CRP,IL-6 and TNF-α in the two groups had no significant difference (P>0.05),but the postoperative level in two groups were significantly higher than those before surgery,and the differences were statistically significant (P<0.05).Before operation,there was no significant difference in ALT,TBiL and GGT between the two groups (P>0.05).On the 7th day after operation,ALT,TBiL and GGT of the two groups decreased,and the observation group was lower than those of the control group (P<0.05).There was no significant difference in visual analogue scale (VAS),postoperative anal exhaust time and postoperative ambulation time between the two groups (P>0.05).The hospitalization time of the observation group was shorter than that of the control group,the difference was statistically significant (P<0.05).The therapeutic effect of the observation group at 3 months after operation was significantly better than that of the control group,the difference was statistically significant (P<0.05).The total incidence of postoperative complications in the observation group was significantly lower than that in the control group,the difference was statistically significant (P<0.05).Conclusion The combination of laparoscopic left hepatectomy and choledochoscopy effectively addresses complex intrahepatic biliary stones,minimally impacting patient stress responses,enhancing liver function,and reducing complication risks,thereby holding promising clinical applicability.

Objective This research assessed the impact of incorporating choledochoscopy with laparoscopic left hepatectomy on stress response and bile duct stone removal in patients presenting with complex intrahepatic biliary stones.Methods Clinical data of 194 patients with complex intrahepatic biliary stones from June 2020 to June 2024 were retrospectively analyzed.The patients were divided into control group (n=97) and observation group (n=97) according to different operation methods.The control group received laparoscopic left hepatectomy,while the observation group received choledochoscopic lithotomy combined with laparoscopic left hepatectomy.The changes of stress indexes[cortisol (Cor),adrenaline (AD)],inflammatory factors[C-reactive protein (CRP),interleukin-6 (IL-6),tumor necrosis factor-α (TNF-α)]in the two groups before and 3 days after operation were compared.The liver function indexes[alanine transaminase (ALT),total bilirubin (TBiL),glutamyl transferase (GGT)]of the two groups before and 7 days after operation were compared.The treatment effect levels of the two groups were evaluated 3 months after operation.The incidence of postoperative complications (bile leakage,infection,residual stones and pleural effusion) was recorded and compared between the two groups.Results Three days before and after operation,the levels of Cor,AD,CRP,IL-6 and TNF-α in the two groups had no significant difference (P>0.05),but the postoperative level in two groups were significantly higher than those before surgery,and the differences were statistically significant (P<0.05).Before operation,there was no significant difference in ALT,TBiL and GGT between the two groups (P>0.05).On the 7th day after operation,ALT,TBiL and GGT of the two groups decreased,and the observation group was lower than those of the control group (P<0.05).There was no significant difference in visual analogue scale (VAS),postoperative anal exhaust time and postoperative ambulation time between the two groups (P>0.05).The hospitalization time of the observation group was shorter than that of the control group,the difference was statistically significant (P<0.05).The therapeutic effect of the observation group at 3 months after operation was significantly better than that of the control group,the difference was statistically significant (P<0.05).The total incidence of postoperative complications in the observation group was significantly lower than that in the control group,the difference was statistically significant (P<0.05).Conclusion The combination of laparoscopic left hepatectomy and choledochoscopy effectively addresses complex intrahepatic biliary stones,minimally impacting patient stress responses,enhancing liver function,and reducing complication risks,thereby holding promising clinical applicability.