Objective To investigate the efficacy of lenalidomide combined with bortezomib and dexamethasone in the treatment of multiple myeloma(MM)and their effects on heat shock protein 90(HSP90)mRNA,miR-28-5p,anti-tartrate acid phosphatase 5b(TRACP-5b)and high mobility group protein B1(HMGB1).Methods Eighty patients with newly diagnosed MM were selected and divided into the two-combination group(40 patients treated with bortezomib and dexamethasone)and the three-combination group(40 patients treated with bortezomib and dexamethasone combined with lenalidomide)according to the treatment modalities.Real-time fluorescence quantitative polymerase chain reaction was used to detect HSP90 mRNA and miR-28-5p levels.Enzyme-linked immunosorbent assay was used to detect TRACP-5b and HMGB1 levels.The clinical efficacy of the 2 groups was compared.Levels of HSP90 mRNA,miR-28-5p,TRACP-5b,HMGB1,the immune cell function,renal function indexes and the incidence of adverse reactions were compared before and after treatment.Results The total effective rate of the three-combination group was higher than that of the two-combination groups(92.50%vs.75.00%,P＜0.05).Compared with the pretreatment,the levels of HSP90 mRNA,TRACP-5b,blood creatinine(SCr),and urea nitrogen(BUN)decreased in the 2 groups after treatment,and which was lower in the three-combination group than that in the two-combination groups.The levels of miR-28-5p,HMGB1,CD4+,CD3+and CD4+/CD8+were elevated in the 2 groups,and the levels were higher in the three-combination group than those in the two-combination group(P＜0.05).There was no significant difference in the incidence of adverse reactions between the two groups.Conclusion Lenalidomide combined with bortezomib and dexamethasone is clinically effective,safe and reliable in the treatment of MM.

Objective To investigate the effect of pecto-intercostal fascial block(PIFB)-PECS Ⅱ block-general anesthesia on hemodynamics and stress response in patients undergoing modified radical mastectomy for breast cancer.Methods A total of 95 patients with breast cancer who underwent modified radical mastectomy in the hospital from November 2021 to November 2023 were enrolled in this study.They were divided into the control group(n=46)and the observation group(n=49)according to the anesthesia mode.The control group received PECS Ⅱ block-general anesthesia and the observation group received PIFB-PECS Ⅱ block-general anesthesia.The dosage of remifentanil,the dosage of cisatracurium,recovery time,tracheal extubation time,postoperative analgesia pump compression times,VAS scores,hemodynamics(HR,MAP),oxidative stress response(SOD,CAT,MDA),and hyperthermia were compared between the two groups Susceptibility to MMSE score and adverse reactions.Results The dosage of remifentanil,dosage of cisatracurium,effective pressing times of analgesia pump within 48 h,wake-up time,tracheal extubation time and time to postoperative first pressing in the observation group were lower and shorter than those in the control group(P＜0.05).The observation group had lower VAS scores than the control group after surgery(P＜0.05).The HR of after anesthesia induction(T1),at tracheal intubation(T2),at the beginning of surgery(T3)and at the end of surgery(T4)in the observation group was(78.45±6.12)times/min,(100.28±11.54)times/min,(103.90±14.82)times/min and(93.66±9.17)times/min,respectively,which were lower than the control group[(84.66±7.04)times/min,(112.33±13.28)times/min,(122.44±17.06)times/min and(106.26±11.03)times/min,respectively].MAP of T1,T2,T3 and T4 in the observation group were(67.73±4.09)mmHg,(75.22±9.51)mmHg,(90.76±10.77)mmHg and(82.50±8.63)mmHg,respectively,the control groups were(70.10±5.66)mmHg,(82.62±10.17)mmHg,(96.43±12.59)mmHg and(90.82±11.04)mmHg,respectively.There was a statistically significant difference between the two groups(P＜0.05).The levels of SOD,CAT and MDA in both groups at 24 hours and 72 hours after the operation were all higher than those before the operation(P＜0.05).The SOD levels in the observation group were(83.22±15.44)nU/ml and(77.41±10.39)nU/ml at 24 h and 72 h after operation.It was lower than that of the control group,which was(90.40±18.23)nU/ml and(82.80±13.18)nU/ml.The CAT scores of observation group were(16.20±5.03)kU/L and(14.12±3.27)kU/L at 24 h and 72 h after operation,which were lower than those of control group[(20.75±6.57)kU/L and(17.06±4.35)kU/L].The MDA levels in the observation group were(5.12±1.33)mmol/L and(3.23±0.76)mmol/L at 24 h and 72 h after surgery,which were lower than those in the control group[(6.03±2.24)mmol/L and(4.88±1.05)mmol/L],and the differences were statistically significant(all P＜0.05).The MMSE scores of the observation group were(28.01±1.35)and(28.46±1.39),which were higher than those of the control group[(26.44±1.08)and(27.36±1.23)](P＜0.05).Conclusion Applying PIFB-PECS Ⅱ block-general anesthesia in modified radical mastectomy for breast cancer can maintain hemodynamic stability,reduce oxidative stress and alleviate the damage to cognitive function,with high safety.

Objective Using network pharmacology research methods and animal pharmacology experiments,explore the mechanism of antidepressant effects of traditional Chinese medicine Citron and Bergamot.Methods Using the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP),ETCM,Symmap,Swiss Target Prediction,and Uniprot data platforms,screen the active ingredients and corresponding gene targets of Citron and Bergamot.Obtain depression gene targets using OMIM,TTD,and Cenecards data platforms.Using Venny 2.1 online software,draw Venn diagrams of the intersection of active ingredients and gene targets.Draw network diagrams between drugs,active ingredients,targets,and diseases using Cytoscape 3.7.2 software.Construct a protein-protein interaction(PPI)network diagram using the STRING data platform for intersecting genes.Using the Metascape data platform,perform gene ontology(GO)function and Kyoto Encyclopedia of Genesand and Genomes(KEGG)pathway enrichment analysis.A rat depression model was established using chronic unpredictable mild stress(CUMS)combined with solitary care,and animal experiments were conducted to verify the BDNF/TrkB/CREB signaling pathway obtained from network pharmacology research.Results The research results of network pharmacology methods show that there are 57 antidepressant active ingredients in Citron,65 antidepressant active ingredients in Bergamot,and important active ingredients include Acetic acid,3,4,7-trimethoxycoumarin and Citric acid,etc.Through the data platform,2717 depression targets and 430 intersection targets were identified.Through PPI network analysis,key gene targets for antidepressant effects in Citron and Bergamot were identified,including TP53,Protein kinase B1,CREB-binding protein,Brain derived neurotrophic factor,etc.Through KEGG analysis,it was found that important signaling pathways include pathways in cancer,PI3K-Akt signaling pathway,Neurotrophin signaling pathway,etc.By observing the neurotrophic factor BDNF/TrkB/CREB signaling pathway in depressed rats,the results showed that the medium dose groups of Citron and Bergamot could significantly increase serum BDNF content(P<0.05),and each treatment group could improve the damage of hippocampal neurons in rats.The high and medium dose groups of Citron and Bergamot significantly increased the expression of BDNF protein in the hippocampal CA1 region(P<0.05,P<0.01).Except for the low-dose group,which showed no difference in TrkB mRNA gene expression,all other treatment groups significantly increased the mRNA gene expression levels of hippocampal BDNF,TrkB and CREB(P<0.01).The medium dose group of Citron and Bergamot increased the expression of BDNF protein in the hippocampus(P<0.01),while the medium and low dose groups significantly increased the relative expression of TrkB protein in the hippocampus(P<0.05).The medium dose group showed an increasing trend in the relative expression of CREB protein.Conclusion Traditional Chinese medicine Citron and Bergamot have therapeutic effects on depression models in rats,and the mechanism of action may be related to the BDNF/TrkB/CREB signaling pathway.

Objective Using network pharmacology research methods and animal pharmacology experiments,explore the mechanism of antidepressant effects of traditional Chinese medicine Citron and Bergamot.Methods Using the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP),ETCM,Symmap,Swiss Target Prediction,and Uniprot data platforms,screen the active ingredients and corresponding gene targets of Citron and Bergamot.Obtain depression gene targets using OMIM,TTD,and Cenecards data platforms.Using Venny 2.1 online software,draw Venn diagrams of the intersection of active ingredients and gene targets.Draw network diagrams between drugs,active ingredients,targets,and diseases using Cytoscape 3.7.2 software.Construct a protein-protein interaction(PPI)network diagram using the STRING data platform for intersecting genes.Using the Metascape data platform,perform gene ontology(GO)function and Kyoto Encyclopedia of Genesand and Genomes(KEGG)pathway enrichment analysis.A rat depression model was established using chronic unpredictable mild stress(CUMS)combined with solitary care,and animal experiments were conducted to verify the BDNF/TrkB/CREB signaling pathway obtained from network pharmacology research.Results The research results of network pharmacology methods show that there are 57 antidepressant active ingredients in Citron,65 antidepressant active ingredients in Bergamot,and important active ingredients include Acetic acid,3,4,7-trimethoxycoumarin and Citric acid,etc.Through the data platform,2717 depression targets and 430 intersection targets were identified.Through PPI network analysis,key gene targets for antidepressant effects in Citron and Bergamot were identified,including TP53,Protein kinase B1,CREB-binding protein,Brain derived neurotrophic factor,etc.Through KEGG analysis,it was found that important signaling pathways include pathways in cancer,PI3K-Akt signaling pathway,Neurotrophin signaling pathway,etc.By observing the neurotrophic factor BDNF/TrkB/CREB signaling pathway in depressed rats,the results showed that the medium dose groups of Citron and Bergamot could significantly increase serum BDNF content(P<0.05),and each treatment group could improve the damage of hippocampal neurons in rats.The high and medium dose groups of Citron and Bergamot significantly increased the expression of BDNF protein in the hippocampal CA1 region(P<0.05,P<0.01).Except for the low-dose group,which showed no difference in TrkB mRNA gene expression,all other treatment groups significantly increased the mRNA gene expression levels of hippocampal BDNF,TrkB and CREB(P<0.01).The medium dose group of Citron and Bergamot increased the expression of BDNF protein in the hippocampus(P<0.01),while the medium and low dose groups significantly increased the relative expression of TrkB protein in the hippocampus(P<0.05).The medium dose group showed an increasing trend in the relative expression of CREB protein.Conclusion Traditional Chinese medicine Citron and Bergamot have therapeutic effects on depression models in rats,and the mechanism of action may be related to the BDNF/TrkB/CREB signaling pathway.

Strengthening the cultivation of innovation ability is the new requirement put forward by the state for higher educa-tion.High-quality curriculum design is the primary means of achieving high-quality talent cultivation.By constructing the"disease case library"and"problem graph"of immune system and related diseases,and adopting the teaching method of"combining large and small cases and integrating online and offline",this study not only consolidates students'basic knowledge,but also builds a bridge for students from theory to practice,from knowledge accumulation to creation and application.It further exercises students'ability to dis-cover,analyze and solve problems,and enhances students'innovation awareness and ability.

Strengthening the cultivation of innovation ability is the new requirement put forward by the state for higher educa-tion.High-quality curriculum design is the primary means of achieving high-quality talent cultivation.By constructing the"disease case library"and"problem graph"of immune system and related diseases,and adopting the teaching method of"combining large and small cases and integrating online and offline",this study not only consolidates students'basic knowledge,but also builds a bridge for students from theory to practice,from knowledge accumulation to creation and application.It further exercises students'ability to dis-cover,analyze and solve problems,and enhances students'innovation awareness and ability.

Objective To investigate the effect of pecto-intercostal fascial block(PIFB)-PECS Ⅱ block-general anesthesia on hemodynamics and stress response in patients undergoing modified radical mastectomy for breast cancer.Methods A total of 95 patients with breast cancer who underwent modified radical mastectomy in the hospital from November 2021 to November 2023 were enrolled in this study.They were divided into the control group(n=46)and the observation group(n=49)according to the anesthesia mode.The control group received PECS Ⅱ block-general anesthesia and the observation group received PIFB-PECS Ⅱ block-general anesthesia.The dosage of remifentanil,the dosage of cisatracurium,recovery time,tracheal extubation time,postoperative analgesia pump compression times,VAS scores,hemodynamics(HR,MAP),oxidative stress response(SOD,CAT,MDA),and hyperthermia were compared between the two groups Susceptibility to MMSE score and adverse reactions.Results The dosage of remifentanil,dosage of cisatracurium,effective pressing times of analgesia pump within 48 h,wake-up time,tracheal extubation time and time to postoperative first pressing in the observation group were lower and shorter than those in the control group(P＜0.05).The observation group had lower VAS scores than the control group after surgery(P＜0.05).The HR of after anesthesia induction(T1),at tracheal intubation(T2),at the beginning of surgery(T3)and at the end of surgery(T4)in the observation group was(78.45±6.12)times/min,(100.28±11.54)times/min,(103.90±14.82)times/min and(93.66±9.17)times/min,respectively,which were lower than the control group[(84.66±7.04)times/min,(112.33±13.28)times/min,(122.44±17.06)times/min and(106.26±11.03)times/min,respectively].MAP of T1,T2,T3 and T4 in the observation group were(67.73±4.09)mmHg,(75.22±9.51)mmHg,(90.76±10.77)mmHg and(82.50±8.63)mmHg,respectively,the control groups were(70.10±5.66)mmHg,(82.62±10.17)mmHg,(96.43±12.59)mmHg and(90.82±11.04)mmHg,respectively.There was a statistically significant difference between the two groups(P＜0.05).The levels of SOD,CAT and MDA in both groups at 24 hours and 72 hours after the operation were all higher than those before the operation(P＜0.05).The SOD levels in the observation group were(83.22±15.44)nU/ml and(77.41±10.39)nU/ml at 24 h and 72 h after operation.It was lower than that of the control group,which was(90.40±18.23)nU/ml and(82.80±13.18)nU/ml.The CAT scores of observation group were(16.20±5.03)kU/L and(14.12±3.27)kU/L at 24 h and 72 h after operation,which were lower than those of control group[(20.75±6.57)kU/L and(17.06±4.35)kU/L].The MDA levels in the observation group were(5.12±1.33)mmol/L and(3.23±0.76)mmol/L at 24 h and 72 h after surgery,which were lower than those in the control group[(6.03±2.24)mmol/L and(4.88±1.05)mmol/L],and the differences were statistically significant(all P＜0.05).The MMSE scores of the observation group were(28.01±1.35)and(28.46±1.39),which were higher than those of the control group[(26.44±1.08)and(27.36±1.23)](P＜0.05).Conclusion Applying PIFB-PECS Ⅱ block-general anesthesia in modified radical mastectomy for breast cancer can maintain hemodynamic stability,reduce oxidative stress and alleviate the damage to cognitive function,with high safety.

Objective To investigate the current status of adverse drug reaction(ADR)monitoring in medical institu-tions under China's pharmacovigilance framework in Guangdong Province,and to propose evidence-based strategies for enhancing institutional monitoring capabilities.Methods A cross-sectional survey was conducted using a structured questionnaire devel-oped in alignment with national regulatory requirements and expert consensus.Data were collected from 65 medical institutions,including general hospitals,traditional Chinese medicine hospitals,and maternal/children's hospitals,across 21 prefecture-level cities in Guangdong.Descriptive and comparative analyses were performed to evaluate institutional practices.Results All 65 in-stitutions submitted valid responses.Among them,63(96.9％)had established standardized ADR reporting protocols,with 93.8％(61/65)delegating oversight to pharmacy departments.ADR data were predominantly collected via institutional informa-tion systems(67.7％,44/65),though these systems focused on passive reporting and basic data aggregation,lacking functional-ities for active signal detection or risk alert mechanisms.Significant disparities(P＜0.05)were observed across hospitals of dif-ferent tiers in reporting modalities,system sophistication,analytical frequency,and early warning implementation.Notably,mo-nitoring practices for conditionally approved drugs(e.g.,emergency-authorized therapeutics)exhibited systemic deficiencies.Conclusions To address these gaps,the following measures are recommended:Accelerating the adoption of intelligent monito-ring systems to enable real-time ADR detection and predictive analytics;Implementing tiered resource allocation policies to ensure equitable capability development;Establishing specialized protocols for high-risk pharmaceuticals,particularly conditionally ap-proved and fast-tracked drugs;Strengthening interdisciplinary training programs to improve pharmacovigilance literacy among healthcare practitioners.These interventions aim to foster a proactive risk management culture and advance patient safety within China's evolving healthcare landscape.

Objective:To study the effects of obesity on alveolar bone loss and gut microbiota in mice with periodontitis.Methods:Twenty-four seven-week-old female C57BL/6J mice were randomly divided into four groups based on table of random numbers ( n=6 in each group): normal-fat diet group (NFD group), high-fat diet group (HFD group), normal-fat diet and periodontitis group (NFD_PD group) and high-fat diet and periodontitis group (HFD_PD group). NFD and HFD groups were fed with normal or high-fat diet for twelve weeks respectively; NFD_PD and HFD_PD groups were induced to periodontitis by ligating the bilateral maxillary second molars with 5-0 silk thread at the fourth week after feeding with normal or high-fat diet respectively. The body weight was measured weekly. The mice were euthanized for collecting the samples at the end of the 12th week. Liver, kidneys, perirenal and retroperitoneal fat were weighed. Serum was collected to detect the level of serum lipids and inflammatory factors. The right maxilla bones were scanned by micro-CT. HE staining was performed to observe the periodontal tissue. The cecum contents were collected for gut microbiota 16S rRNA gene sequencing. Spearman correlation analysis was performed to analyze the correlation between the abundance of gut microbiota and serum inflammatory level and CT value. Results:After 12 weeks of high-fat diet fed, the body weight of HFD group [(26.52±1.96) g] was significantly higher than that of NFD group [(20.95±0.63) g] ( t=6.63, P<0.001). The body weight of HFD_PD group [(23.82±1.12) g] was significantly higher than that of NFD_PD group [(20.73±0.47) g] ( t=6.23, P=0.001). The serum levels of total cholesterol, triglyceride and low density lipoprotein in HFD group and HFD_PD group were significantly higher than those in NFD group and NFD_PD group ( P<0.01). The distance from the cemento-enamel junction to the alveolar bone crest (CEJ-ABC) on the mesial site of maxillary second molar in HFD_PD group [(647.46±47.46) μm] was significantly higher than that in NFD_PD group [(440.48±68.08) μm] ( t=5.58, P<0.001). HE staining showed that the maxillary second molar attachment loss, collagen fiber destruction and inflammatory cell infiltration were more significant serious in HFD_PD group compared with NFD_PD group. The levels of interleukin (IL)-1β, IL-6 and monocyte chemotactic protein-1 (MCP-1) of serum in HFD_PD group [(17.11±1.92), (31.61±3.20) and (204.42±35.96) ng/L, respectively] were significantly higher than those in NFD_PD group [(10.44±1.65), (19.96±2.09) and (147.36±10.76) ng/L, respectively] ( P<0.001, P<0.001, P=0.004). The 16S rRNA gene analysis revealed that the Bacteroides/Firmicutes ratio in HFD_PD group (4.00±3.30) was significantly higher than that in NFD_PD group (0.62±0.19) ( t=2.50, P=0.030). The abundance of Oscillospira in HFD_PD group [(12.25±0.05) %] was significantly higher than that in NFD_PD group [(2.80±0.01) %] ( t=4.64, P<0.001). The abundance of Parabacteroides in HFD_PD group [(0.25±0.27)% ] was significantly lower than that in NFD_PD group [(2.04±0.02)%] ( t=2.32, P=0.043). The β-diversity analysis of gut microbiota based on Bray-Curtis distance showed that samples of HFD_PD group and NFD_PD group were obviously grouped. Correlation analysis showed that the abundance of Oscillospira was positively correlated with IL-1β, IL-6, MCP-1 concentration and CEJ-ABC value in serum significantly ( r values were 0.80, 0.79, 0.80, 0.89, P<0.05). The abundance of Parabacteroides was negatively correlated with IL-1β, IL-6 concentration and CEJ-ABC value in serum significantly ( r values were -0.71, -0.71, -0.86, -0.95, P<0.05). Conclusions:Obesity promotes alveolar bone resorption in periodontitis mice and changes the gut microbiota. Oscillospira and Parabacteroides may play a key role.

Objective To explore the relationship between the triglyceride glucose(TyG)index and 2-year cognitive function changes.Methods A total of 101 elderly patients who were hospitalized at Quanzhou First Hospital Affiliated to Fujian Medical University from September to December 2022 were selected.The cognitive function was evaluated using Montreal cognitive assessment(MoCA)scale.According to the baseline TyG index,the subjects were divided into high TyG index group(TyG index≥ 8.79,51 cases)and low TyG index group(TyG index＜8.79,50 cases).Using a binary Logistic regression model to adjust for confounding factors,the association between TyG index and cognitive decline was analyzed.Results The Spearman correlation analysis results showed that TyG index was negatively correlated with the change value of cognitive function(r=-0.243,P＜0.05).The incidence of cognitive function decline in high TyG index group was significantly higher than that in low TyG index group(43.1％vs.24.0％,P=0.042).After adjusting for confounding factors,the risk of cognitive function decline in high TyG index group was 2.971 times that of low TyG index group(P＜0.05).Conclusion The TyG index of elderly hospitalized patients is correlated with 2-year cognitive function changes.The TyG index may serve as a potential biomarker for early detection of cognitive function decline.