Aim To investigate the protective effects of co-administered piperine on reversing the skeletal deterioration induced by fluoxetine.Methods Female ovariectomized rats were orally administered with estra-diol,fluoxetine,piperine and the mixture of piperine and fluoxetine for eight weeks,respectively.X-ray ab-sorption assay was used to determine bone mineral den-sity(BMD).microCT was used to analyze the effects of drug treatments on micro-architecture,three-bending test was performed to examine the biomechanical prop-erties.ELISA kits were employed to quantify the bone turnover markers in serum.Besides,rat primary osteo-blasts were cultured to investigate the osteoblastogene-sis and mineralization in the presence of fluoxetine with or without piperine.Results Compared with ovariec-tomized rats,the administration of estradiol and piper-ine significantly enhanced BMD and biomechanical properties with improved micro-architecture of trabecu-lar bones.Fluoxetine treatment further deteriorated BMD,biomechanical properties and micro-architecture of ovariectomized rats with accelerated bone turnover.Concomitant administration of piperine with fluoxetine significantly suppressed the deteriorating effects on skeleton by fluoxetine.In addition,fluoxetine reduced the differentiation and mineralization of primary osteo-blasts,whereas combined therapy showed promotional effects.Conclusions The administration of fluoxetine induces further bone loss in ovariectomized rats by in-hibiting osteoblastic differentiation and mineralization.The co-administration of piperine with fluoxetine rever-ses its skeletal deterioration.

Objective To compare the efficacy of blood letting under pain point touch and ultrasound-guided puncture de-compression in the treatment of acute supraspinatus muscle calcifying tendinitis.Methods From January 2020 to January 2023,45 patients with acute supraspinatus muscle calcifying tendinitis were selected and divided into treatment group and control group.In the treatment group,a total of 22 patients were treated with ultrasound-guided puncture decompression,in-cluding 16 females and 6 males,aged from 20 to 64 years old(39.31±5.80)years old,11 on the left shoulder and 11 on the right shoulder.In the control group,there were 23 cases,including 15 females and 8 males,aged from 19 to 66 years old(40.67±6.13)years old,12 on the left shoulder and 13 on the right shoulder.The treatment was treated with pain point touch bloodletting therapy.The visual analog scale(VAS)pain score,University of California,Los Angeles(UCLA)shoulder system score and shoulder Constant-Murley score were used to evaluate the therapeutic effect before treatment,1 weeks,1 month and 3 months after treatment,respectively.Results One patient in the control group gave up follow-up for personal reasons after 1 week of treatment,and the other 44 patients completed all follow-up.Six months after treatment,there were no recurrence cases in both groups.After statistical analysis,VAS pain score,UCLA score and Constant-Murley score of the treatment group and the control group were significantly different from those before treatment(P＜0.05),and the improvement was more obvious in the treatment group.There was no statistical significance between the two groups(P＞0.05).Conclusion Bloodletting under pain point touch and ultrasound-guided puncture decompression are effective in the treatment of acute calcific supraspinatus tendinitis,with simple operation and low cost,which can effectively reduce local pain and effectively improve shoulder joint function.Primary hospitals can selectively operate treatment according to their own conditions.

Objective:To investigate expression and significance of mitochondrial ribosomal protein L37(MRPL37)in colorectal cancer.Methods:RNA-seq data and clinical information of colorectal cancer patients were obtained from the TCGA and GEO databases to analyze the differ-ential expression,clinicopathological features,and prognosis of MRPL37 in colorectal cancer.En-richment analysis was performed to explore the biological functions and signaling pathways in-volved in MRPL37,and the TISID database was analyzed for the correlation between MRPL37 and immune-infiltrating cells.Results:MRPL37 was found to be significantly overexpressed in colorectal cancer(P＜0.05)and was significantly correlated with the T-stage(P=0.0041),N-stage(P=0.0053),and TNM-stage(P=0.0159)of colorectal cancer patients.The enrichment analysis indi-cates that MRPL37 is primarily involved in mitochondrial physiological activities,cell cycle,oxida-tive phosphorylation,and immune pathways in colorectal cancer.Regarding tumor immunity,changes in MRPL37 expression were found to be correlated with changes in multiple types of im-mune cells in the tumor microenvironment.MRPL37 was an independent prognostic factor(P=0.011),and its expression level was positively associated with patient prognosis(P=0.0017).Con-clusion:MRPL37 may serve as a new potential biomarker for colorectal cancer,which can be used in the future to predict patient prognosis and guide precise patient treatment.

Three recipients with portal vein thrombosis experienced insufficient blood flow to transplanted liver due to residual thrombus after thrombectomy during liver transplantation. Alternative measures posed significant risks or technical challenges. To promptly restore blood flow, intraoperative intervention was performed via round ligament of donor liver for managing residual portal vein thrombus. Balloon dilation and vascular stenting effectively relieved local stenosis. After intervention, portal vein flow rate and volume fulfilled the standards and function of transplanted liver recovered smoothly. Follow-ups revealed unobstructed stents and no new thrombus formation. This simple, safe and efficacious technique has not been previously reported in the literature.

Objective:To evaluate the clinical efficacy of acupuncture in the treatment of anxiety state in patients with primary insomnia(PI). Methods:Randomized controlled trials of acupuncture treatment for PI patients with an anxiety state in Web of Science,Cochrane Library,PubMed,Excerpta Medica Database(EMBASE),China National Knowledge Infrastructure(CNKI),Wanfang Data Knowledge Service Platform(Wanfang),and Chongqing VIP Database(VIP)were retrieved by computer.The retrieval time was from each database's inception to December 30,2022.Data extraction and evaluation were performed for the included studies.The Cochrane risk of bias assessment tool was used to assess the risk of bias in each article.Meta-analysis of valid data was performed using the RevMan 5.4 software.If the outcome indicator was a categorical variable,relative risk(RR)was used as the effect size.If it was a continuous variable,mean difference(MD)was used to calculate the effect size.Each effect size was expressed as a 95%confidence interval(CI).P<0.05 was considered to indicate a statistically significant difference. Results:A total of 18 studies were included,comprising a total of 1198 patients.The findings of the meta-analysis showed that electroacupuncture had a significant advantage in improving the Hamilton anxiety scale(HAMA)score than benzodiazepines[MD=-1.61,95%CI(-2.17,-1.06),P<0.001].Acupuncture was superior to sham acupuncture[MD=-14.90,95%CI(-20.39,-9.41),P<0.001]and benzodiazepines[MD=-3.39,95%CI(-4.67,-2.12),P<0.001]in reducing the self-rating anxiety scale(SAS)score.Acupuncture was superior to sham acupuncture in reducing the insomnia severity index(ISI)score[MD=-5.61,95%CI(-6.63,-4.89),P<0.001].Acupuncture was superior to benzodiazepines[MD=0.84,95%CI(-1.42,-0.25),P=0.005]and sham acupuncture[MD=-8.39,95%CI(-8.39,-7.86),P<0.001]in improving the Pittsburgh sleep quality index(PSQI)score.Acupuncture had a better effective rate than benzodiazepines[RR=1.16,95%CI(1.08,1.25),P<0.001]and sham acupuncture[RR=8.94,95%CI(4.63,17.25),P<0.001]in treating PI. Conclusion:Acupuncture or electroacupuncture has certain therapeutic advantages over benzodiazepines and sham acupuncture in the treatment of anxiety in PI patients.However,more high-quality randomized controlled trials are needed for further verification.

Drug resistance presents a significant challenge to achieving positive clinical outcomes in anti-tumor therapy.Prior research has illuminated reasons behind drug resistance,including increased drug efflux,alterations in drug targets,and abnormal activation of oncogenic pathways.However,there's a need for deeper investigation into the impact of drug-resistant cells on parental tumor cells and intricate crosstalk between tumor cells and the malignant tumor microenvironment(TME).Recent studies on extracellular vesicles(EVs)have provided valuable insights.EVs are membrane-bound particles secreted by all cells,mediating cell-to-cell communication.They contain functional cargoes like DNA,RNA,lipids,proteins,and metabolites from mother cells,delivered to other cells.Notably,EVs are increasingly recognized as regulators in the resistance to anti-cancer drugs.This review aims to summarize the mechanisms of EV-mediated anti-tumor drug resistance,covering therapeutic approaches like chemo-therapy,targeted therapy,immunotherapy and even radiotherapy.Detecting EV-based biomarkers to predict drug resistance assists in bypassing anti-tumor drug resistance.Additionally,targeted inhibition of EV biogenesis and secretion emerges as a promising approach to counter drug resistance.We highlight the importance of conducting in-depth mechanistic research on EVs,their cargoes,and functional ap-proaches specifically focusing on EV subpopulations.These efforts will significantly advance the devel-opment of strategies to overcome drug resistance in anti-tumor therapy.

Parkinson's disease (PD) is a chronic neurodegenerative disease. At present, levodopa and other drugs are mainly used for dopamine supplementation therapy. However, the absorption of levodopa in the gastrointestinal tract is unstable and its half-life is short, and long-term use of levodopa will lead to the end-of-dose deterioration, dyskinesia, the "ON-OFF" phenomenon and other symptoms. Therefore, new preparations need to be developed to improve drug efficacy, reduce side effects or improve compliance of patients. Based on the above clinical needs, this review briefly introduced the preparation modification strategies for the treatment of PD through case analysis, in order to provide references for the research and development of related preparations.

Osteonecrosis of the femoral head(ONFH)is a common orthopedic disease,and hip preservation surgery has high clinical value in the early stages of ONFH,especially for young and middle-aged patients.However,the repair of ONFH is heterogeneous,leading to inter-individual variations in the efficacy of hip preservation.Currently,the existing tissue-engineered scaffolds in the field of hip preservation are uncontrollable after implantation,making it difficult to achieve precise repair.Smart responsive materials have good biocompatibility and self-feedback capability.By combining them with therapeutic drugs to construct stimulus-responsive drug delivery systems,new possibilities are provided for the precise repair of ONFH.This paper reviews the research progress of smart responsive materials at home and abroad.Based on the response principles of various materials and the repair characteristics of ONFH,the application prospects of various smart responsive materials such as reactive oxygen species-responsive,fluid shear stress-responsive,and light/magnetic-responsive materials are discussed and prospected in the field of precise repair for ONFH,providing new ideas for the precise treatment of ONFH.

OBJECTIVE: To observe the effect of acupotomy on the fat infiltration degree of lumbar multifidus muscle (LMM) in patients with lumbar disc herniation after percutaneous transforaminal endoscopic discectomy (PTED). METHODS: A total of 104 patients with lumbar disc herniation treated with PTED were randomly divided into an observation group (52 cases, 3 cases dropped off) and a control group (52 cases, 4 cases dropped off). Patients of both groups received rehabilitation training of two weeks 48 h after PTED treatment. The observation group was treated with acupotomy (L₃-L₅ Jiaji [EX-B 2]) once within 24 h after PTED. In the two groups, the fat infiltration cross sectional area (CSA) of LMM was compared before and 6 months after PTED, the visual analogue scale (VAS) score and Oswestry disability index (ODI) score were observed before and 1, 6 months after PTED. The correlation between fat infiltration CSA of LMM in each segment and VAS score was analyzed. RESULTS: Six months after PTED, the fat infiltration CSA of LMM in L₄/L₅ and the total L₃-S₁ segments of the observation group was lower than that before PTED (P<0.05), and the fat infiltration CSA of LMM in L₄/L₅ of the observation group was lower than the control group (P<0.01). One month after PTED, the ODI and VAS scores of the two groups were lower than those before PTED (P<0.01), and those in the observation group were lower than the control group (P<0.05). Six months after PTED, the ODI and VAS scores of the two groups were lower than those before PTED and 1 month after PTED (P<0.01), and those in the observation group were lower than the control group (P<0.01). There was a positive correlation between the fat infiltration CSA of LMM in the total L₃-S₁ segments and VAS scores in the two groups before PTED (r = 0.64, P<0.01). Six months after PTED, there was no correlation between the fat infiltration CSA of LMM in each segment and VAS scores in the two groups (P>0.05). CONCLUSION Acupotomy can improve the fat infiltration degree of LMM, pain symptoms and activities of daily living in patients with lumbar disc herniation after PTED.
Humans ; Intervertebral Disc Displacement ; Activities of Daily Living ; Paraspinal Muscles ; Treatment Outcome ; Lumbar Vertebrae ; Retrospective Studies ; Endoscopy ; Diskectomy ; Acupuncture Therapy

OBJECTIVE: To observe the clinical significance of translocator proteins (TSPO) gene in the treatment of FLT3-ITD/DNMT3A R882 double-mutated acute myeloid leukemia (AML). METHODS: Seventy-six patients with AML hospitalized in the Department of Hematology of the Affiliated People's Hospital of Ningbo University from June 2018 to June 2020 were selected, including 34 patients with FLT3-ITD mutation, 27 patients with DNMT3A R882 mutation, 15 patients with FLT3-ITD/DNMT3A R882 double mutation, as well as 19 patients with immune thrombocytopenia (ITP) hospitalized during the same period as control group. RNA was routinely extracted from 3 ml bone marrow retained during bone puncture, and TSPO gene expression was detected by transcriptome sequencing (using 2-deltadeltaCt calculation). RESULTS: The expression of TSPO gene in FLT3-ITD group and DNMT3A R882 group at first diagnosis was 2.02±1.04 and 1.85±0.76, respectively, which were both higher than 1.00±0.06 in control group, but the differences were not statistically significant (P=0.671, P=0.821). The expression of TSPO gene in the FLT3-ITD/DNMT3A R882 group was 3.98±1.07, wich was significantly higher than that in the FLT3-ITD group and DNMT3A R882 group, the differences were statistically significant (P=0.032, P=0.021). The expression of TSPO gene in patients who achieved complete response after chemotherapy in the FLT3-ITD/DNMT3A R882 group was 1.19±0.87, which was significantly lower than that at first diagnosis, and the difference was statistically significant (P=0.011). CONCLUSION TSPO gene may be used as an indicator of efficacy in FLT3-ITD /DNMT3A R882 double-mutated AML.
Humans ; DNA (Cytosine-5-)-Methyltransferases/genetics* ; DNA Methyltransferase 3A ; Mutation ; Leukemia, Myeloid, Acute/drug therapy* ; Nucleophosmin ; Prognosis ; fms-Like Tyrosine Kinase 3/genetics* ; Receptors, GABA/therapeutic use*