Objective To analyze the efficacy and safety of denosumab(DEN)in the treatment of type 2 diabetes mellius(T2DM)complicated with osteoporosis(OP).Methods The DEN's efficacy on bone metabolism and glucose metabolism in patients with T2DM and OP was retrospectively analyzed through a before-and-after self-controlled design.Forty-one T2DM patients combined with OP who were treated in The First Hospital of Changsha from January 2022 to December 2022 were selected.All patients were observed with subcutaneous injection of DEN 60 mg every 6 months for 12 months.The changes of HbA1c,FPG,bone metabolism indexes,25-hydroxyvitamin D[25(OH)D]and bone mineral density(BMD)of patients before and after DEN treatment were compared.The adverse reactions of DEN were recorded.Results After 12 months of treatment,25(OH)D,the BMD oflumbar vertebra(L1～4),left femoral neck and left hip were higher than before treatment(P<0.05),while the osteocalcin,β-collagen special series,parathyroid hormone and alkaline phosphatase were lower than before treatment(P<0.05),and the adverse reactions were reduced.Conclusions DEN can significantly improve bone metabolism in patients with T2DM and osteoporosis,increase BMD of lumbar spine and whole hip with fewer adverse reactions.

Objective To observe the effects of electroacupuncture auricular acupuncture points on depression-like behaviors and ventral dorsal tegmental area(VTA)TH,DRD1 and DRD2 induced in well acute stress disorder(ASD)mice.Methods Experiment 1:18 male C57 mice were divided into 9 control and 9 model mice.Behavioural paradigms such as forced swimming test(FST)and tail suspension test(TST)were used to detect depression-like behaviors in the mice starting on day 5 and day 36;double-labelled staining for immediate early gene protein(C-Fos)and tyrosine hydroxylase(TH)was detected in the VTA of the mice by immunofluorescence.Experiment 2:45 male C57 mice were divided into 15 mice each in the control groups,model groups and electroacupuncture groups.30 days after completion of the electroacupuncture intervention,the mice were tested for depressive behaviors using behavioural paradigms such as FST and TST;dopamine receptor D1(DRD1)and dopamine receptor D2(DRD2)was detected in the VTA of mice in each group using fluorescence quantitative PCR and Western blot techniques;the number of TH neurons in the brain area of the VTA of mice was observed by immunofluorescence.Results Experiment 1:Compared with the control group,the immobile duration of the model group increased in the TST(P<0.001)and FST(P<0.001)on day 5 and day 6,and the immobile duration of the model group increased in the TST(P<0.01)and FST(P<0.01)on day 36 and day 37;compared with the control group,the number of C-Fos and TH fluorescence double-labelled neurons in the model group increased(P<0.05).Experiment 2:At day after completion of the electroacupuncture intervention,the immobile duration of TST(P<0.01)and FST(P<0.01)were decreased in the electroacupuncture group compared with the model group;compared with the control group,DRD1 mRNA(P<0.001)and protein expression(P<0.01)were increased in the VTA of the electroacupuncture group,and DRD2 mRNA(P<0.001)and protein expression(P<0.05)were decreased,TH protein expression(P<0.05)increased,and the number of TH neurons increased(P<0.01).Conclusion Early intervention with auricular electroacupuncture points has an ameliorative effect on depression-like behaviors induced by acute stress disorder in mice,which may be achieved by modulating the activity level of dopaminergic neurons and the expression level of DRD1 and DRD2 in the VTA.

Objective To analyze the composition characteristics and biological functions of tumor cell subpopulations in glioblastoma(GBM)through multi-transcriptomics sequencing technology,and explore the hypoxia characteristics and spatial localization features of the mesenchymal-like(MES-like)tumor cell subpopulation in GBM and the influence on malignant biological behaviors.Methods Multi-transcriptomics sequencing data,including single-cell RNA sequencing(scRNA-seq)data(18 patients),bulk RNA sequencing(bulk RNA-seq)and spatial transcriptomics(ST)data of GBM,were employed to define cell subpopulations in GBM,and Gene Ontology(GO)and Gene Set Enrichment Analysis(GSEA)were utilized to analyze their functions.The proportions and locations of cell subpopulations in bulk RNA-seq data were evaluated with BayesPrism deconvolution.Immunofluorescence assay was conducted for verification on 12 paraffin samples of GBM from patients who visited the neurosurgical department of our hospital from 2015 to 2023 and met the pathological diagnostic criteria for GBM(10 males and 2 females,at an average age of 53.50 years and a median age of 54.50 years).pySCENIC was applied to predict specific transcription factors of tumor cell subpopulations.Results Tumor cells in GBM were highly heterogeneous,and could be mainly divided into 4 subpopulations:astrocyte-like(AC-like),neural progenitor-like(NPC-like),oligodendrocyte progenitor-like(OPC-like)and MES-like.Differential gene analysis found that the MES-like tumor cells highly expressed vascular endothelial growth factor A(VEGFA),adrenomedullin(ADM),N-myc downstream regulated 1(NDRG1),insulin like growth factor binding protein 5(IGFBP5),and A-kinase anchoring protein 12(AKAP12)(P<0.001).pySCENIC transcription factor prediction found that the high-active transcription factors of the MES-like tumor cells were AT-rich interaction domain 3A(ARID3A),FOS like 2,AP-1 transcription factor subunit(FOSL2),endothelial PAS domain protein 1(EPAS1),CCAAT enhancer binding protein delta(CEBPD),and CCAAT enhancer binding protein beta(CEBPB)(P<0.05).GO and GSEA enrichment analyses found that the MES-like tumor cells were enriched in hypoxia-related pathways,especially the pathway of cell responses to hypoxia levels(NES=2.437,P<0.001).BayesPrism deconvolution showed that the MES-like tumor cells mainly existed in PAN(Pseudopalisading cells around necrosis)and perinecrotic zone.Immunofluorescence assay confirmed CD44+(CD44 antigen)MES-like tumor cells were mainly located in hypoxia areas with highly expression of hypoxia inducible factor 1 subunit alpha(HIF1α)(P<0.01).Multivariate Cox regression analysis indicated that the MES-like tumor cells were significantly correlated with the adverse prognosis of GBM patients(HR=1.71,95%CI:1.38～2.11,P<0.001).Conclusion Tumor cells in GBM are of highly heterogeneity.They could be mainly divided into 4 subpopulations:AC-like,NPC-like,OPC-like and MES-like.MES-like tumor cells,mainly locating in PAN and perinecrotic zone,are characterized by hypoxia,which can promote the malignant progression of GBM.

OBJECTIVE: To investigate the effectiveness of endoscopic-assisted median nerve decompression with one-stage extensor indicis proprius (EIP) tendon transfer for reconstruction of thumb abduction in patients with severe carpal tunnel syndrome (CTS). METHODS: The clinical data of 12 patients with severe CTS who met the selection criteria between December 2019 and December 2024 were retrospectively analyzed. There were 2 males and 10 females with an average age of 55.4 years ranging from 35 to 67 years. The symptom duration of CTS was 12-120 months (mean, 48.7 months) and the thenar muscle atrophy duration was 6-48 months (mean, 13.4 months). The median nerve was released with the help of endoscope, and the EIP tendon was transferred to reconstruct the abduction function of the thumb. The operation time and complications were recorded. Two-point discrimination, palmar abduction angle of the thumb, radial abduction angle of the thumb, and pinch force of the thumb were measured and compared before operation and at last follow-up, and the effectiveness was evaluated by Kapandji score and Disabilities of the Arm, Shoulder and Hand (DASH) score. The satisfaction of the operation was evaluated at last follow-up. RESULTS: All surgeries were successfully completed with a mean operation time of 54 minutes (range, 45-68 minutes). All patients were followed up 6-50 months, with an average of 15.3 months. There was no complications such as wound infection, scar pain of wrist, or tendon rupture of transposition, and there were 3 cases of mild limitation of finger extension in the donor site of index finger. At last follow-up, two-point discrimination, palmar abduction angle of the thumb, radial abduction angle of the thumb, Kapandji score, and DASH score were significantly better than those before operation ( P<0.05), but there was no significant difference in thumb pinch force between pre- and post-operation ( P>0.05). The evaluation of surgical satisfaction showed that 7 cases were very satisfied and 5 cases were satisfied. CONCLUSION The combination of endoscopic-assisted median nerve decompression and one-stage EIP tendon transfer effectively improves hand function and quality of life in patients with severe CTS by restoring thumb abduction and alleviating neurological symptoms.
Humans ; Tendon Transfer/methods* ; Male ; Middle Aged ; Carpal Tunnel Syndrome/physiopathology* ; Female ; Decompression, Surgical/methods* ; Aged ; Adult ; Thumb/physiopathology* ; Endoscopy/methods* ; Retrospective Studies ; Median Nerve/surgery* ; Treatment Outcome ; Plastic Surgery Procedures/methods*

Objective To investigate the impact of pharmaceutical services provided by clinical pharmacists on rational drug use and cost control in hepatobiliary surgery under the Diagnosis Related Groups(DRGs)payment model,aming to provide evidence for improving the rationality of drug therapy and saving medical costs.Methods Patients classified under DRGs disease codes HB15,HB13,and HB11 from November 2022 to April 2024 were selected as study subjects.A total of 195 patients were included,with 106 in the intervention group and 89 in the control group.The intervention group received multidimensional clinical pharmaceutical services in addition to the standard care provided to the control group.The rational drug use rate,medication costs,total hospitalization expenses,and length of hospital stay were observed between the two groups.A cost-benefit analysis was employed to evaluate the economic impact of providing pharmaceutical services to hepatobiliary surgical patients.The cost indicator was the clinical pharmacy services cost,and the benefit indicators were the reductions in total hospitalization expenses and medication costs.The benefit-cost ratio(B/C)was calculated,and sensitivity analysis was performed.Results The intervention group showed significantly higher rational use rates of prophylactic antimicrobial agents(drug selection:83.96％vs.46.07％,P＜0.01;treatment duration:84.91％vs.56.18％,P＜0.01)and parenteral nutrition drugs(97.17％vs.73.03％,P＜0.01)compared to the control group.Additionally,the intervention group had significantly reduced the length of hospital stay,total hospitalization expenses,medication costs,and insurance over-expenditure compared to the control group(P＜0.05).Furthermore,clinical pharmacist intervention led to a reduction in medication costs by 4 320.05(2 555.00,5 088.25)yuan(CNY)and total hospitalization expenses by 8 891.12(5 135.05,10 074.03)yuan(CNY).The B/C ratios were 14.24(8.42,16.77)and 29.30(16.92,33.20),respectively,indicating economic efficiency.Sensitivity analysis supported these results.Conclusion Under the DRGs payment model,clinical pharmaceutical services guided by drug therapy pathways contribute to improving rational drug use in hepatobiliary surgery and provide clear economic benefits,playing a positive role in reducing medical costs.

AIM: To observe the clinical outcomes of Phorcides analytic engine-assisted topography-guided personalized laser assisted in situ keratomileusis(LASIK)for the treatment of myopia and astigmatism in virgin eyes with the refractive astigmatism significantly deviating from corneal topography.METHODS: Retrospective clinical study. A total of 32 cases(42 eyes)with myopia and astigmatism that received corneal topography-guided personalized LASIK in the Ophthalmology Refractive Surgery Center of the First Affiliated Hospital of Xi'an Jiaotong University from December 2019 to March 2021 were selected. The uncorrected distance visual acuity(UDVA), best corrected distance visual acuity(CDVA), refractive state and aberrations before and at 6 mo after surgery were recorded.RESULTS: There were 15 males and 17 females, with an age of 23.00(18.00, 29.25)years old; preoperative sphere was -5.75(-6.25, -4.00)D, and cylinder was -0.75(-1.38, -0.25)D. At 6 mo postoperatively, the UDVA exceeded the preoperative CDVA in 19 eyes(45%). The spherical equivalent(SEQ)of all eyes(100%)was -0.50 to +0.50 D at 6 mo postoperatively, and the postoperative SEQ of 23 eyes(55%)was -0.13 to +0.13 D. There were 33 eyes(79%)had a postoperative astigmatism ≤ 0.25 D, the target-induced astigmatism(TIA)was 0.94±0.96 D, and the surgically induced astigmatism(SIA)was 0.94±0.86 D, with no statistical significance between TIA and SIA(P>0.05). The astigmatism axial deviation ranged from -5° to +5° in 33 eyes(79%)at 6 mo postoperatively. Compared to pre-operation, the total higher-order aberrations and spherical aberrations within the central 6 mm diameter of the anterior corneal surface increased at 6 mo postoperatively(Z=-3.778, P<0.001; Z=-4.929, P<0.001); the postoperative coma aberrations had no change(Z=-1.763, P=0.078); the postoperative trefoil aberrations decreased(Z=-2.490, P=0.013). Compared to pre-operation, the Strehl ratio of the anterior corneal surface increased significantly at 6 mo after surgeries(t=-5.401, P=0.013).CONCLUSION: Using the Phorcides analytic engine to assist topography-guided personalized LASIK for the treatment of myopia and astigmatism in virgin eyes with the refractive astigmatism significantly deviating from topography-measured astigmatism can achieve good therapeutic effects. Postoperative UDVA exceeded preoperative CDVA in nearly half of the eyes, and the quality of postoperative corneal imaging was improved.

Objective:To observe the effect of electroacupuncture on depression in chronic pain mice; To explore its mechanism.Methods:36 C57BL/6J mice were divided into a blank control group, a sham-operation group, a model group, and an electroacupuncture group using a random number table method, with 9 mice in each group. The chronic compression injury model of sciatic nerve was established in the model group and electroacupuncture group. Mechanical pain threshold (MWT) and latent heat wave leg reflex (TWL) were measured on preoperative day 1 and postoperative days 4, 7, 14, 21, and 35. Electroacupuncture treatment was performed on the 14th day after modeling, and on the 35th day after modeling, open field experiments, elevated cross maze experiments, forced swimming experiments, and tail suspension experiments were conducted to evaluate depressive like behavior in mice. Western blot was used to detect the protein expressions of glutamate receptor 1 (GluA1), glutamate receptor 2 (GluA2), human glucose transporter 3 (GLUT3), and calmodulin dependent protein kinase Ⅱ (CaMKⅡ) in the hippocampus of each group of mice; GluA1 positive cells in the hippocampus of mice was observed using immunofluorescence technology.Results:Compared with the blank group, the MWT and TWL value of the model group decreased ( P<0.05) on postoperative days 4, 7, 14, and 21. Compared with the model group, the electroacupuncture group had a longer stay time in the central area of the open field ( P<0.01), an increased percentage of stay time and activity frequency in the elevated arm opening ( P<0.01), a shorter static time for forced swimming ( P<0.01), and a shorter immobility time for the suspended tail ( P<0.01). Compared with the model group, the expressions of GluA1, GLUT3, GluA2, and CaMKⅡ proteins in the hippocampus of mice in the electroacupuncture group increased ( P<0.05), and the number of GluA1 positive cells increased ( P<0.05). Conclusion:Electroacupuncture can affect synaptic plasticity by regulating the AMPA receptor in the hippocampal region, thereby improving depressive mood caused by chronic pain.

Objective:To evaluate the value of ultrasound radiomics combined with machine learning for early diagnosis of seronegative Hashimoto’s thyroiditis (SN-HT) .Methods:This retrospective study included 164 patients from Liaoning Provincial People’s Hospital , Lixin County People’s Hospital, Linghai Dalinghe Hospital, Fengcheng Phoenix Hospital, who underwent thyroidectomy for solitary nodules with normal thyroid function between Nov. 2016 and Jan. 2024. Postoperative pathology confirmed Hashimoto’s thyroiditis (HT) in some cases, who were further categorized into antibody-positive and antibody-negative groups based on serum antibody status. Patients without Hashimoto’s thyroiditis served as the control group. A total of 298 ultrasound images were analyzed. Radiomics features were extracted from hypoechoic non-nodular areas within 0.5 cm surrounding the tumor. Two senior pathologists and two senior ultrasound physicians independently assessed lymphocytic infiltration, eosinophilic changes of follicular epithelium, and the proportion of hypoechoic areas in pathology and ultrasound images, respectively. A machine learning model, CCH-NET, was developed using linear regression and t-distributed stochastic neighbor embedding (t-SNE) techniques. The dataset was divided into a training set (80%) and a validation set (20%) to compare the diagnostic accuracy of CCH-NET with that of senior ultrasound physicians. Results:In internal validation, CCH-NET achieved a diagnostic accuracy of 88.89% for both antibody-positive and antibody-negative groups, significantly higher than the 66.67% accuracy of senior ultrasound physicians ( P<0.01). In external validation, CCH-NET achieved 75.00% and 66.67% accuracy for the two groups, compared to 50.00% by senior ultrasound physicians. For the control group, both methods achieved 93.33% accuracy. The AUC of CCH-NET was 0.848, outperforming senior ultrasound physicians (0.681) ,demonstrating superior diagnostic performance. Conclusion:The radiomics-based CCH-NET model, using non-nodular hypoechoic areas as a specific indicator, can accurately identify early SN-HT in euthyroid patients. It significantly outperforms senior ultrasound physicians, improving diagnostic accuracy and reducing missed diagnoses.

Objective:To evaluate the value of ultrasound radiomics combined with machine learning for early diagnosis of seronegative Hashimoto’s thyroiditis (SN-HT) .Methods:This retrospective study included 164 patients from Liaoning Provincial People’s Hospital , Lixin County People’s Hospital, Linghai Dalinghe Hospital, Fengcheng Phoenix Hospital, who underwent thyroidectomy for solitary nodules with normal thyroid function between Nov. 2016 and Jan. 2024. Postoperative pathology confirmed Hashimoto’s thyroiditis (HT) in some cases, who were further categorized into antibody-positive and antibody-negative groups based on serum antibody status. Patients without Hashimoto’s thyroiditis served as the control group. A total of 298 ultrasound images were analyzed. Radiomics features were extracted from hypoechoic non-nodular areas within 0.5 cm surrounding the tumor. Two senior pathologists and two senior ultrasound physicians independently assessed lymphocytic infiltration, eosinophilic changes of follicular epithelium, and the proportion of hypoechoic areas in pathology and ultrasound images, respectively. A machine learning model, CCH-NET, was developed using linear regression and t-distributed stochastic neighbor embedding (t-SNE) techniques. The dataset was divided into a training set (80%) and a validation set (20%) to compare the diagnostic accuracy of CCH-NET with that of senior ultrasound physicians. Results:In internal validation, CCH-NET achieved a diagnostic accuracy of 88.89% for both antibody-positive and antibody-negative groups, significantly higher than the 66.67% accuracy of senior ultrasound physicians ( P<0.01). In external validation, CCH-NET achieved 75.00% and 66.67% accuracy for the two groups, compared to 50.00% by senior ultrasound physicians. For the control group, both methods achieved 93.33% accuracy. The AUC of CCH-NET was 0.848, outperforming senior ultrasound physicians (0.681) ,demonstrating superior diagnostic performance. Conclusion:The radiomics-based CCH-NET model, using non-nodular hypoechoic areas as a specific indicator, can accurately identify early SN-HT in euthyroid patients. It significantly outperforms senior ultrasound physicians, improving diagnostic accuracy and reducing missed diagnoses.

Objective To observe the effects of electroacupuncture auricular acupuncture points on depression-like behaviors and ventral dorsal tegmental area(VTA)TH,DRD1 and DRD2 induced in well acute stress disorder(ASD)mice.Methods Experiment 1:18 male C57 mice were divided into 9 control and 9 model mice.Behavioural paradigms such as forced swimming test(FST)and tail suspension test(TST)were used to detect depression-like behaviors in the mice starting on day 5 and day 36;double-labelled staining for immediate early gene protein(C-Fos)and tyrosine hydroxylase(TH)was detected in the VTA of the mice by immunofluorescence.Experiment 2:45 male C57 mice were divided into 15 mice each in the control groups,model groups and electroacupuncture groups.30 days after completion of the electroacupuncture intervention,the mice were tested for depressive behaviors using behavioural paradigms such as FST and TST;dopamine receptor D1(DRD1)and dopamine receptor D2(DRD2)was detected in the VTA of mice in each group using fluorescence quantitative PCR and Western blot techniques;the number of TH neurons in the brain area of the VTA of mice was observed by immunofluorescence.Results Experiment 1:Compared with the control group,the immobile duration of the model group increased in the TST(P<0.001)and FST(P<0.001)on day 5 and day 6,and the immobile duration of the model group increased in the TST(P<0.01)and FST(P<0.01)on day 36 and day 37;compared with the control group,the number of C-Fos and TH fluorescence double-labelled neurons in the model group increased(P<0.05).Experiment 2:At day after completion of the electroacupuncture intervention,the immobile duration of TST(P<0.01)and FST(P<0.01)were decreased in the electroacupuncture group compared with the model group;compared with the control group,DRD1 mRNA(P<0.001)and protein expression(P<0.01)were increased in the VTA of the electroacupuncture group,and DRD2 mRNA(P<0.001)and protein expression(P<0.05)were decreased,TH protein expression(P<0.05)increased,and the number of TH neurons increased(P<0.01).Conclusion Early intervention with auricular electroacupuncture points has an ameliorative effect on depression-like behaviors induced by acute stress disorder in mice,which may be achieved by modulating the activity level of dopaminergic neurons and the expression level of DRD1 and DRD2 in the VTA.