OBJECTIVE To investigate the targeting effect of folic acid-modified crebanine nanoparticles （FA-Cre@PEG- PLGA NPs， hereinafter referred to as “NPs”） combined with ultrasound irradiation on M109 cells in vitro and in vivo after administration， and explore the anti-tumor mechanism. METHODS CCK-8 assay was used to detect the inhibitory effect of NPs combined with ultrasound irradiation on the proliferation of M109 cells， and the best ultrasound time was selected. Using human lung cancer A549 cells as a control， the targeting of NPs combined with ultrasound irradiation to M109 cells was evaluated by free folic acid blocking assay and cell uptake assay. The effects of NPs combined with ultrasound irradiation on the migration， invasion， apoptosis， cell cycle and reactive oxygen species （ROS） levels of M109 cells were detected by cell scratch test， Transwell chamber test and flow cytometry at 1 h after 958401536@qq.com administration； the changes of mitochondrial membrane potential （MMP） were observed by fluorescence inverted microscope. A mouse subcutaneous tumor model of M109 cells was constructed， and the in vivo tumor targeting of NPs combined with ultrasound irradiation was investigated by small animal in vivo imaging technology. RESULTS NPs combined with ultrasound irradiation could significantly inhibit the proliferation of M109 cells， and the optimal ultrasound time was 1 h after administration. The free folic acid could antagonize the inhibitory effect of NPs on the proliferation of M109 cells， and combined with ultrasound irradiation could partially reverse this antagonism. Compared with A549 cells， the uptake rate of NPs in M109 cells was significantly higher （P＜0.01）， and ultrasound irradiation could promote cellular uptake. NPs combined with ultrasound irradiation could inhibit the migration and invasion of M109 cells and block the cell cycle in the G0/G1 and G2/M phases. Compared with control group， the apoptosis rate of M109 cells and ROS level were increased significantly （P＜0.01）， while the MMP decreased significantly （P＜0.01） in the different concentration （100， 200， 300 μg/mL） groups of M109 cells. Compared with the mice in non-ultrasound group， the fluorescence intensity and tumor-targeting index of the tumor site in the 0 h ultrasound group were significantly enhanced （P＜0.05 or P＜0.01）. CONCLUSIONS NPs combined with ultrasound irradiation have a strong targeting effect on M109 cells in vitro and in vivo， the anti-tumor mechanism includes inhibiting cell migration and invasion， blocking cell cycle， and inducing apoptosis.

OBJECTIVE To explore the significance of pharmaceutical care through the diagnosis and treatment of a patient with exogenous insulin autoimmune syndrome （EIAS）， combined with the analysis of literature reports. METHODS Clinical pharmacist participated in the diagnosis and treatment process of one case of EIAS. Based on the characteristics of the patient’s condition， the pharmacist provided medication suggestions and formulated pharmaceutical monitoring measures. At the same time， the pharmacist searched for relevant literature on insulin autoimmune syndrome （IAS） and EIAS， extracted data （gender， age， occurrence time， laboratory tests， clinical symptoms， intervention and outcome）， and conducted analysis. RESULTS Based on the patient’s medication information in the past 3 years， clinical pharmacist determined that the EIAS was likely caused by insulin aspartate 30. The clinician adopted the clinical pharmacist’s suggestion to discontinue insulin and switch to oral hypoglycemic drugs. The patient improved after treatment. The literature analysis showed that among the 257 patients with IAS reported， 212 cases were caused by drugs； among them， 23 cases were caused by lipoic acid， and 56 cases were caused by exogenous insulin. There were no significant differences in age， glycosylated hemoglobin， and body mass index between the two groups. The lowest blood glucose level in the lipoic acid group was significantly lower than that in the exogenous insulin group （P＜0.05）. The proportion of females and the proportion of fasting insulin ≥ 1 000 μU/mL were significantly higher in the lipoic acid group than in the exogenous insulin group （P＜0.05）. CONCLUSIONS Compared with EIAS， lipoic acid-induced IAS usually causes more severe hypoglycemia， and the fasting insulin level is usually higher than 1 000 μU/mL， which is more common in female patients. The participation of clinical pharmacists in the diagnosis and treatment of EIAS can help improve the diagnosis and treatment level of similar rare diseases and ensure the safety of patients’ medication.

OBJECTIVE To investigate the preferences of patients who underwent solid organ transplantation regarding therapeutic drug monitoring （TDM） of mycophenolic acid （MPA） and explore the factors influencing patients’ decision-making process， so as to provide support for the development of individualized medication guidelines for MPA and improvement of clinical decision-making. METHODS The cross-sectional study was used to design the questionnaire on the patients’ preferences to accept MPA TDM， and involved patients who underwent solid organ transplantation and received MPA treatment at two tertiary hospitals in Beijing from April 14， 2022， to June 27， 2022. The Likert 5-level scoring method was used to score the patients’ preferences to accept MPA TDM， the influencing factors and their correlation of the patients’ preferences to accept MPA TDM were analyzed by Pearson correlation analysis and binary Logistic regression analysis， and the nonparametric test and chi-square test were used to rank and analyze the consistency of the factors affecting patients’ preference decision. RESULTS A total of 140 questionnaires were collected， and the effective recovery rate was 77.35%. The average preference score of 140 patients to receive MPA TDM was （4.01±0.65）， and the overall preference value was high. There were 116 （82.86%） patients agreed or strongly agreed with MPA TDM. Significant differences were observed in preference scores between patients who had previously undergone MPA TDM and those who had never undergone it （[ 4.30±0.53） scores vs. （3.80±0.65） scores， P＜0.001]. Additionally， patients’ preference scores were significantly influenced by their understanding level and attention level （P＜0.001）. The ranking of factors contributing to decision-making exhibited consistency （P＜0.001）. The factors were ranked in descending order of clinical efficacy， safety， comfortability， economy and time cost. CONCLUSIONS The patients who underwent solid organ transplantation hold high preferences towards MPA TDM. The primary factors influencing their decisions are their prior experience， understanding level， and attention level.

Objective:To construct a risk identification model based on dynamic Bayesian network(DBN),and to explore its application value in the operation management of orthopedic equipment in hospital.Methods:Risk factors in orthopedic equipment management were identified based on DBN model,and risk evaluation index set was established to provide early warning and prevention for possible risk factors.12 pieces of orthopedic medical equipment in clinical use in The Second Affiliated Hospital of Air Force Medical University from January 2020 to February 2022 were selected,the traditional orthopedic equipment quality operation management method(referred to as traditional mode)and the DBN-based risk identification mode(referred to as DBN mode)were adopted for equipment management respectively.The equipment operation effects,risk incidence rates and treatment efficiency of the two modes were compared.Results:The start-up operation efficiency and equipment quality qualification rate of the equipment in DBN mode were(93.54±4.05)%and(97.51±6.68)%,respectively,which were higher than those in the traditional mode;the troubleshooting time and the equipment component damage rate were(7.14±1.64)hours and(0.48±0.11)%,respectively,which were lower than those in the traditional mode,the difference was statistically significant(t=8.862,8.228,32.994,73.047,P<0.05).The function failure rate,parts damage rate,unqualified cleaning and disinfection rate and improper management rate of equipment in 479 equipment usage data,897 operations,300 equipment disinfection records and 500 equipment daily inspection records in the DBN mode were 0.21%(1/479),0.33%(3/897),1.33%(4/30)and 2.0%(10/500),respectively,which were lower than those in the traditional mode,the difference was statistically significant(x2=21.527,12.964,3.485,6.914,P<0.05).The effective rate of 500 cases of orthopedic medical equipment treatment of DBN mode was 97.8%(489/500),which was significantly higher than that of traditional mode,the difference was statistically significant(x2=12.617,P<0.05).Conclusion:The application of risk identification model based on DBN to the management of orthopedic medical equipment in hospital can strengthen the quality of orthopedic equipment management,improve the efficiency of equipment operation and treatment,and prevent and avoid equipment risks.

Objective:To analyze the clinic effects of arthroscopic partial trapeziectomy and suture button suspensionplasty in the treatment of first carpometacarpal joint (CMCJ) Eaton stage II/III arthrosis.Methods:A retrospective study was conducted on a total of 15 cases (16 hands) of patients including 5 males (1 bilateral) and 10 females with CMCJ stage II/III arthrosis who underwent surgical treatment at the first affiliated hospital of Shenzhen university from January 2020 to June 2022, with mean age of 56.7±6.4 years (range, 46-75 years). The duration from pain to treatment was 7.8±3.2 months (range, 4-14 months). X-ray showed narrowing of CMCJ with osteophytes and distal radial subluxation. All the patients were treated with arthroscopic partial trapeziectomy and suture button suspensionplasty. The preoperative and last postoperative follow-up radiographs, visual analogue scale (VAS), thumb's Kapandji scores, disabilies of the arm, shoulder, and hand (DASH) scores, grip and pinch strength and time to return to work were compared.Results:All cases were followed up for 19.6±6.3 months (range, 11-36 months). The postoperative X-ray showed all the CMCJs were reduced with a normal height of first metacarpal. The mean time for patients to return to their daily activities was 18.69±3.70 d and the mean time to return to work was 24.63±4.91 d. The average VAS score decreased from 6.56±1.15 preoperatively to 1.00 (0.75, 1.25). The preoperative Kapandji's score was 8.00±0.82 and the postoperative Kapandji's score was 8.00 (7.25, 9.00). The average DASH values improved from 24.06±3.19 to 4.00 (3.00, 5.00). The were significant differences except for Kapandji score ( Z=-4.905, P<0.001; Z=-0.121, P=0.905; Z=-4.846, P<0.001). The mean grip and pinch strength showed improvement from an average of 16.4 (14.13, 18.68) kg and 1.70±0.35 kg to 26.14±3.27 kg and 3.58±0.91 kg with significant difference ( Z=-4.617, P<0.001; t=-7.669, P<0.001). Conclusion:Arthroscopic partial trapeziectomy and suture button suspensionplasty is a minimally invasive surgery for the treatment of first CMCJ Eaton stage II/III arthrosis. By this technique, the patients' existing instability and pain problems can be solved.

Objective To investigate the therapeutic efficacy of dandelion extract on intracerebral hemorrhage(ICH)rats and its effect on nuclear factor erythroid 2 related factor 2(Nrf2)/heme oxygenase-1(HO-1)signaling pathway.Methods Stereotaxic intracranial injection of type Ⅳ col-lagenase was used to establish rat ICH model.Then 48 ICH rats were randomly divided into mod-el group,dandelion extract group,Nrf2 inhibitor(ML385)group and dandelion extract+ML385 group,with 12 rats in each group.Another 12 rats served as sham operation group.After treat-ment,neurological deficits was evaluated and scored for all groups of rats.Blood-brain barrier(BBB)function,neuronal apoptotic rate in the hippocampus,serum levels of COX-2,IL-6 and iNOS,cerebral contents of CAT,GSH-Px,ROS and MAD,and protein levels of Nrf2/HO-1 signal pathway were detected.Results Compared with sham operation group,the neurological deficit score,Evans blue exudation,appptotic rate of hippocampal neurons,serum COX-2,IL-6,iNOS levels,brain tissue reactive oxygen species(ROS)and malondialdehyde level in the model group were significantly increased(P＜0.05),and the expression levels of CAT,GSH-Px,Nrf2 and HO-1 proteins were significantly decreased(P＜0.05).Compared with dandelion extract group,combination of dandelion extract and ML385 significantly increased the neurological deficit score(2.54±0.23 vs 1.43±0.19),Evans blue exudation[(22.15±3.61)ng/mg vs(6.54±1.24)ng/mg],apoptotic rate[(31.97±5.26)％vs(3.51±0.94)％],serum COX-2[(5.82±1.16)ng/ml vs(1.34±0.42)ng/ml],IL-6[(1.47±0.31)ng/ml vs(0.43±0.14)ng/ml]and iNOS levels[(59.91±10.36)U/ml vs(13.94±3.78)U/ml],brain tissue ROS[(4.70±0.45)U/kg vs(1.70± 0.51)U/kg]and MDA levels[(3.72±0.52)nmol/mg vs(1.17±0.34)nmol/mg],and decreased expression levels of CAT[(2.54±0.59)U/mg vs(5.68±1.04)U/mg],GSH-Px[(8.01±0.86)U/mg vs(16.97±3.03)U/mg],Nrf2(0.67±0.13 vs 1.07±0.19)and HO-1(0.55±0.07 vs 0.86± 0.10,P＜0.05).Conclusion Dandelion extract can enhance the antioxidant activity in ICH rats by activating Nrf2/HO-1 signaling pathway,prevent the progression of inflammation and oxida-tive stress,inhibit neuronal apoptosis in hippocampus,repair blood-brain barrier function,and thus improve nerve function.

Objective To investigate the effect of fibroblast growth factor receptor 3(FGFR3)on articular cartilage superficial zone cells(SPZCs).Methods C57 mice were randomly divided into two groups:a sham operated group(sham group)and a group of surgically induced unstable medial meniscus model group(DMM group).The histological morphology of articular cartilage was microscopied by Safranin O/Fast Green-stained in 4 weeks and 8 weeks after surgery.Apoptosis and FGFR3 protein expression were detected by immunohistochemical staining mi-croscopy.Primary SPZCs were separated and randomly divided into control group and Fgfr3 knockdown treatment group.The genes and protein expression related to chondrocyte extra cellular matrix synthesis,degradation and chondrocytehypertrophy were detected by RT-qPCR and Western blot.Results Compared with the sham group,the keen cartilage of mice in DMM group showed a pioneer damage of SPZCs after surgery;Immunohistochemistry results showed an increase in chondrocyte apoptosis and a decrease in expression of MMP-13 and FGFR3(P＜0.05).Primary SPZCs were transfected with small interfering RNA(siRNA)to knockdown Fgfr3;RT-qPCR results showed that the mRNA expression of genes related to the synthesis of cartilage extracellular matrix aggrecan and Col2 was reduced;And the mRNA expression of extracellular matrix degradation-related genes Mmp13 and Adamts5 was increased.The mRNA expression of chondrocyte hypertrophy-related genes Col10 and Mmp13 was increased.Western blot and RT-qPCR results were consistent and the expression l of MMP13 protein was significantly increased,while the expression of collagenⅡand aggrecan protein was significantly decreased(P＜0.05).Conclusions Knockdown of Fgfr3 induces damage to primary SPZCs in mice resulting in early osteoarthritis(OA)development.

Objective:To explore the impact of CACNA1C rs58619945 genotype on the cortical thickness of attentional networks in patients with Bipolar 1 disorder type (BD-Ⅰ). Methods:From August 2013 and August 2019, a total of 155 BD-Ⅰ patients were recruited from the outpatient and inpatient Departments of the Affiliated Brain Hospital of Guangzhou Medical University, along with 82 healthy controls (HC) from the community and university. Genotype for the CACNA1C rs58619945 locus was determined for all BD-I patients and HC subjects, followed by 3.0 T magnetic resonance imaging scans to measure the cortical thickness in the alert, orienting, and executive control subnetworks. General linear models (GLMs) were used to evaluate the impact of CACNA1C rs58619945 on the cortical thickness of attentional networks. Concurrently, attentional dimension functions were assessed using repeatable battery for the assessment of neuropsychological status (RBANS) and Cambridge neuropsychological test automated battery rapid visual information processing (CANTAB RVP) test. This study was approved by the Medical Ethics Committee of the Affiliated Brain Hospital of Guangzhou Medical University(Ethics No. 2023-056). Results:Compared with the HC group, the BD-Ⅰ patients had shown reduced thickness in bilateral prefrontal cortex, bilateral posterior cingulate cortex, and bilateral superior temporal cortex( P<0.05). A significant interaction between the CACNA1C genotype and the cortical thickness(HC vs.BD) of right prefrontal cortex, right posterior parietal cortex and right superior temporal cortex was noted( P<0.05). Partial correlation analysis has demonstrated a significant correlation between CANTAB RVP and RBANS attention indices and cortical thickness in the right prefrontal cortex, right posterior cingulate cortex( P<0.05), and right superior temporal cortex predominantly among carriers of the BD-Ⅰ G allele. Conclusion:The G allele of CACNA1C rs58619945 is associated with cortical thickness of the right prefrontal cortex, right posterior cingulate cortex, and right superior temporal cortex in BD-Ⅰ, which are part of the alerting and orienting network.

Background Bipolar disorder is a severe mental disorder characterized by cycling between mania/hypomania and depression,yet its underlying pathophysiological mechanism remains unclear.Several prior studies have suggested a potential role for voltage-gated calcium channel subunit genes in the etiology of bipolar disorder,particularly in their influence on brain structure.Objective To investigate the differences in grey matter volume(GMV)for individuals with bipolar disorder compared to healthy controls,and to explore the potential influence of calcium channel voltage-dependent T-type α1 G subunit(CACNA1G)rs757415 polymorphism on GMV in bipolar disorder and clarify the specific brain regions associated with this genetic variation,thus offering a new opportunity to gain insight into the pathophysiological mechanism of bipolar disorder.Methods A cohort of 289 patients who met the Diagnostic and Statistical Manual of Mental Disorders,fourth edition(DSM-IV)criteria for bipolar disorder were selected for participation.These patients were either admitted to hospital or examined in outpatient clinic for bipolar disorder at the Mental Health Center of West China Hospital,Sichuan University between September 2013 and December 2022.Another 322 healthy individuals were concurrently recruited as a control group from Sichuan University and surrounding communities.All participants underwent brain imaging using a 3.0 T magnetic resonance scanner to acquire data on GMV.Additionally,the presence of the CACNA1G rs757415 polymorphism was validated using the imLDRTM technique.Spearman correlation analysis was utilized to investigate potential relationship between abnormal brain regions identified through GMV data and clinical characteristics of the patients.Then the genotype-by-diagnosis interaction effect for CACNA1G rs757415 on GMV was observed using the full factor method.Results The study successfully enrolled 173 patients with bipolar disorder and 207 healthy controls who completed all the necessary procedures.Analyses revealed decreased GMV for patients with bipolar disorder compared to healthy controls in the left cerebellar declive extending to cerebellar anterior/posterior lobe,fusiform gyrus,parahippocampal gyrus and inferior occipital gyrus(t=5.664,P<0.05);in the right cerebellar anterior/posterior lobe,fusiform gyrus,parahippocampal gyrus extending to lingual gyrus(t=4.583,P<0.05);in the bilateral anterior cingulate/paracingulate gyri,superior frontal gyrus and precuneus(t=7.543,P<0.05);in the left lingual gyrus and superior temporal gyrus(t=6.593,P<0.05);and in the right insula entending to central operculum(t=7.153,P<0.05).Correlation analysis indicated that the duration of bipolar disorder was positively correlated with cerebrospinal fluid volume(r=0.258,P=0.003),whereas negatively correlated with the GMV in the left cerebellar declive extending to cerebellar anterior/posterior lobe,inferior occipital gyrus and parahippocampal gyrus(r=-0.204,P=0.019),in the right cerebellar anterior lobe extending to right cerebellar posterior lobe,fusiform gyrus,parahippocampal gyrus and lingual gyrus(r=-0.238,P=0.006),in the bilateral superior frontal gyrus extending to anterior cingulate/paracingulate gyri and precuneus(r=-0.219,P=0.012),in the left lingual gyrus extending to superior temporal gyrus(r=-0.296,P=0.001),and in the right insula extending to central operculum(r=-0.257,P=0.003).A significant genotype-by-diagnosis interaction effect for CACNA1G rs757415 on GMV was observed in the right parahippocampal gyrus-fusiform gyrus-cerebellum 4-5(F=19.967,P<0.05).In the control group,individuals carrying the non-risk allele showed increased GMV in the right parahippocampal gyrus-fusiform gyrus-cerebellum 4-5 compared to those carrying the risk allele.In contrast,within the patient group,risk allele carriers exhibited increased GMV in the same brain regions when compared to non-risk allele carriers.Moreover,the GMV in the right parahippocampal gyrus-fusiform gyrus-cerebellum 4-5 of patients with bipolar disorder carrying risk alleles was increased compared to healthy controls.Conclusion CACNA1G rs757415 polymorphism may affect the GMV in the right parahippocampal gyrus,fusiform gyrus and cerebellum 4/5 of patients with bipolar disorder.

Objective·To study the alterations in vestibular hair cell morphology and function of ATPase plasma membrane Ca2+transporting 2 oblivion(Atp2b2 Oblivion)heterozygous mice at different ages.Methods·Atp2b2 Oblivion heterozygous male mice aged 2 months and 8 months were selected with ten in each kind and C57BL/6J wild-type mice with the same gender,age and number were selected as the control group.Expression patterns of ATP2B2 in vestibular hair cells and numbers of hair cells in the striola zone and the extra striola zone in the two groups of mice at different ages were observed and calculated respectively through immunofluorescence assay.Hair bundle structures were detected by scanning electron microscopy(SEM),and mitochondria and ribbon synapse structures were observed by transmission electron microscopy(TEM).Vestibular evoked potential(VsEP),vestibular evoked myogenic potential(VEMP),rotarod rod test,and balance beam test were adopted for the evaluation of vestibular functions.Results·ATP2B2 was mainly expressed in the hair bundle of vestibular hair cells in the two groups of mice.Hair cell numbers in the striola zone and the extra-striola zone did not exhibit any differences between Atp2b2 Oblivion heterozygous mutant mice and wild-type mice of 2-month-old and 8-month-old.No visible structural abnormality in the hair bundle could be seen through SEM.TEM results implied no morphological abnormality in mitochondria or ribbon synapses in the 2-month-old heterozygous mutant mice,while vacuolar degeneration was discovered in the mitochondria under the cuticular plate in the 8-month-old heterozygous mutant mice with the normal ribbon synapses and the normal mitochondria near the innervation site.VsEP and VEMP thresholds of 2-month-old and 8-month-old Atp2b2 Oblivion heterozygous mutant mice were significantly elevated compared with the wild-type mice.Analysis of VsEP waveform manifested prolonged P1 latency and declined P1N1 amplitude in heterozygous mutant mice(P＜0.05).Results of rotarod rod test and balance beam test acquired from 2-month-old Atp2b2 Oblivion heterozygous mutant mice were not significantly different from the wild-type mice,while the ability of the mutant mice to accomplish the tests descended significantly at 8 months of age compared with the wild-type mice(P＜0.05).Conclusion·Atp2b2 Oblivion heterozygous mutant mice showed defective vestibular electrophysiological function at 2 months old,and abnormalities in vestibule-related behaviors can be detected at 8 months old.The vestibular function ofAtp2b2 Oblivion heterozygous mutant mice deteriorate progressively.