Objective To analyze the effect of Hsa-circ-0101216 on gemcitabine(GEM)chemotherapy resistance in pancreatic cancer and its mechanism.Methods Differentially expressed circRNAs between GEM-resistant pancreatic cancer cells and parent cells were screened using the GEO database.Pancreatic cancer GEM resistant cell lines(BxPC-3-GEM and Capan-1-GEM)were constructed by intermittent concentration gradient method.qRT-PCR was used to detect the expression of Hsa-circ-0101216 in cells.GEM resistant pancreatic cancer cell lines were taken and divided into sh-circ-0101216 group(knockdown of circ-0101216),sh-NC group(transfected with sh-NC),and blank control group(untreated).CCK-8 assay and EdU proliferation assay were used to detect the half inhibitory concentration(IC50)of GEM and proliferation ability of cells in each group.Western blotting was performed to detect the expression of multidrug resistance-related protein 1(MRP1),breast cancer resistance protein(BCRP),and human equilibrative nucleoside transporter-1(hENT-1).A subcutaneous xenograft tumor model of human pancreatic cancer in nude mice was constructed,and sh-NC+GEM group and sh-circ-0101216+GEM group(n=6)were set up.The volume and weight of xenograft tumor in nude mice were compared between the two groups.Western blotting and immunohistochemistry were used to detect the expression of MRP1,BCRP,and hENT-1 proteins in xenograft tumor tissues,and EDU proliferation assay was used to detect the proliferation ability of tumor cells.Results The GEO database screening showed that Hsa-circ-0101216 was up-regulated in GEM-resistant pancreatic cancer cell lines.Pancreatic cancer GEM-resistant cell lines were successfully constructed,and the expression levels of Hsa-circ-0101216 and the IC50 value in GEM-resistant pancreatic cancer cells BxPC-3-GEM and Capan-1-GEM were significantly higher than those in parental cells(P<0.05).In sh-circ-0101216 group,the IC50 values of GEM,cell viability,EdU positivity rate,and the expression levels of MRP1 and BCRP proteins in GEM-resistant pancreatic cancer cells BxPC-3-GEM and Capan-1-GEM were significantly lower than those in blank control group and sh-NC group,while the expression level of hENT-1 protein was significantly higher(P<0.05 or P<0.001).In sh-circ-0101216+GEM group,the weight and volume of subcutaneous xenograft tumors in nude mice,the expression levels and positive expression rates of MRP1 and BCRP proteins in tumor tissues,and the EdU positive rate were significantly lower than those in sh-NC+GEM group,while the expression level and positive expression rate of hENT-1 protein were significantly higher(P<0.05).Conclusions Hsa-circ-0101216 is highly expressed in GEM-resistant pancreatic cancer cell lines.Its knockdown can inhibit the proliferation of pancreatic cancer cells and enhance the chemosensitivity of pancreatic cancer cells to GEM.The mechanism may be related to the regulation of transmembrane transporter protein expression.

Objective:To explore the therapeutic effect of Bupiqiangli compound on experimental myasthenia gravis with sub-clinical hypothyroidism in rats and the influence of hypothalamus-pituitary-thyroid-thymus(HPTT)axis.Methods:SPF Lewis rats were randomly divided into normal group,model group,Bupiqiangli compound low-dose,medium-dose and high-dose groups.Model rats were immunized with AchR-α subunit 97-116 peptide sequence to construct an experimental myasthenia gravis model,and then methimazole was used to prepare an experimental myasthenia gravis with subclinical hypothyroidism model.Bupiqiangli compound low-dose,medium-dose and high-dose groups were given 4.57 g/kg,7.12 g/kg and 9.49 g/kg of Bupiqiangli compound by gavage,nor-mal group and model group were given an equal volume of normal saline by gavage,once a day,for 4 weeks.After the last gavage,Lennon scores of rats in each group were recorded;HE staining was used to detect pathological changes of thymus and thyroid;ELISA was used to detect expression levels of acetylcholine receptor antibody(AchRab),thyroid stimulating hormone(TSH),thyrotropin releasing hormone(TRH),free thyroxine(FT4)and thyroxine(T4)in serum;mRNA level of TRH in hypothalamus and TSH in pituitary tissue were detected by qPCR;Western blot detected changes of protein expressions of Cleaved Caspase3,Bcl2 associated X protein(Bax)and B-cell lymphoma-2(Bcl2)in thymus.Results:Compared with normal group,model group showed obvious symp-toms of muscle weakness,Lennon score increased significantly(P<0.05),obvious pathological changes in thymus and thyroid tissues,while no significant changes in expressions of FT4 and T4 in serum(P>0.05),expressions of AchRab,TSH and TRH in serum were significantly increased(P<0.05),expressions of TRH in hypothalamus and TSH in pituitary were significantly increased(P<0.05),protein expressions of Cleaved Caspase3 and Bax in thymus were significantly decreased(P<0.05),while expression of Bcl2 protein in thymus increased significantly(P<0.05).Compared with model group,myasthenia symptoms of compound high-dose group were im-proved,Lennon score was significantly decreased(P<0.05),pathological changes of thymus and thyroid tissues were improved,ex-pressions of FT4 and T4 in serum had no significant changes(P>0.05),expressions of AchRab,TSH and TRH in serum were signifi-cantly decreased(P<0.05),expressions of TRH in hypothalamus and TSH in pituitary were significantly decreased(P<0.05),expres-sions of Cleaved Caspase3 and Bax in thymus were significantly increased(P<0.05),while expression of Bcl2 in thymus was signifi-cantly decreased(P<0.05).Conclusion:Bupiqiang compound can improve clinical symptoms of experimental myasthenia gravis with subclinical hypothyroidism in rats,and its mechanism may be related to the regulation of HPTT axis.

The telomere structure in the cell nucleus is crucial for maintaining the stability and functions of chromosomes.Telomerase is a ribonucleoprotein reverse transcriptase,which catalyzes the elongation of telomeres using its own RNA as a template,thereby counteracting the shortening of telomeres caused by chromosome replication and cell division.Due to its overexpression in over 85％of malignant tumor cells,telomerase has emerged as a highly promising biomarker and a novel target for cancer therapy.In recent years,given the importance of precise quantification of telomerase activity in guiding medical diagnosis and treatment strategies,researchers have developed various high-performance telomerase detection techniques.Among these,electrochemical biosensing technique has cause much attention due to its high sensitivity,operational convenience,rapid response,and ease of miniaturization.This paper focused on the latest advances in electrochemical sensing technique for detection of telomerase activity,aiming to provide inspiration for designing novel telomerase activity detection strategies by elucidating three unique properties of telomerase primer extension products.

Thoracolumbar spine fracture often leads to severe pain, functional impairments, and neurological deficits, for which open reduction and internal fixation can effectively restore the spinal structural stability. Open decompression and reduction with internal fixation can help relieve spinal cord compression and improve spinal function in cases of concomitant cord injury. Although spinal stability can be restored through surgery, patients often face chronic pain and functional impairments postoperatively. A postoperative rehabilitation program is critical in optimizing therapeutic outcomes, reducing complications, and minimizing the risk of secondary injuries. However, current rehabilitation methods, such as physical therapy, functional training, and pain management, are confronted with problems in clinical practice, including significant variation in efficacy, poor patient adherence, and prolonged rehabilitation period. There is an urgent need for a unified rehabilitation strategy to address these problems. To this end, the Spinal Trauma Group of the Orthopedic Physicians Branch of the Chinese Medical Association and the Spine Health Professional Committee of the Chinese Human Health Technology Promotion Association organized experts from relevant fields to formulate Evidence-based guidelines for rehabilitation treatment after internal fixation of thoracolumbar spine fracture in adults ( version 2025) by integrating evidences from clinical researches and advanced rehabilitation concepts at home and abroad. A total number of 14 recommendations concerning the rehabilitation treatment with multimodal analgesia, psychological intervention, deep vein thrombosis prevention, core muscle and extremity exercise, appropriate use of braces, early weight-bearing, device-aided rehabilitation exercise, neuroregulatory therapy, rehabilitation team were put forward, aiming to standardize the post-operative rehabilitation process following internal fixation, promote the functional recovery, and enhance patients′ quality of life.

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.

Objective:To evaluate the effect of acupuncture on postoperative delirium (POD) in diabetic patients undergoing surgery under general anesthesia.Methods:In this randomized controlled trial, 92 diabetic patients of either sex, aged 30-80 yr, with a body mass index of 18-28 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, scheduled for elective surgery under general anesthesia, were divided into 2 groups ( n=46 each) using a table of random numbers: control group (group C) and acupuncture group (group A). Group A received acupuncture at the Baihui (GV20), Shenting (GV24) and Sishencong (EX-HN1) acupoints before anesthesia. The needles were retained for 30 min, with manual stimulation applied every 10 min for 10 s each time. After 4 stimulations, routine anesthesia was carried out. Group C received routine anesthesia only. Regional cerebral oxygen saturation was recorded on admission to the operating room (T 0), after anesthesia induction (T 1), at the start of surgery (T 2), at the end of surgery (T 3), and immediately after tracheal extubation (T 4). The POD developed within 3 days after surgery was assessed. The occurrence of needle-related adverse effects such as fainting, subcutaneous bleeding, and local paresthesia was recorded. Results:Compared with group C, the incidence of POD was significantly reduced, and the regional cerebral oxygen saturation was increased at T 1, 4 in group A ( P<0.05). Conclusions:Acupuncture can decrease the development of POD in diabetic patients undergoing surgery under general anesthesia, which is related to an increase in regional cerebral oxygen saturation.

Objective:To evaluate the safety and efficacy of mild hypothermia arch-clamping technique in the surgical treatment of DeBakey Type Ⅰ aortic dissection.Methods:From December 2019 to November 2023, a total of 97 patients with DeBakey type Ⅰ aortic dissection who underwent arch-clamping technique in Beijing Anzhen Hospital were prospectively enrolled. The patients were divided into mild hypothermia group and moderate hypothermia group according to the lowest rectal temperature during the circulatory arrest period. The perioperative data of the two groups were compared, and complex adverse outcomes consisting of 30-day death, stroke, paraplegia and CRRT were used as the primary endpoint. Multivariate logistic regression was used to determine the predictors of clinical adverse outcomes. Survival analysis was evaluated by the Kaplan- Meier method. Results:The overall incidence of complex adverse outcomes was 20.6%, 13.6% in the mild hypothermia group and 22.7% in the moderate hypothermia group( P=0.535), and the incidence of stroke was 4.6% and 6.7%( P=1.000), respectively. The cardiopulmonary bypass time and aortic-clamping time in the mild hypothermia group were significantly shortened (147.5 min vs. 163.0 min, P=0.032; 89 min vs. 99 min, P=0.042). There was no significant difference in long-term survival and reintervention between the two groups(91.9% vs. 89.3%, P=0.87; 9.1% vs. 5.3%, P=0.13). Conclusion:Mild hypothermia arch-clamping technique is a safe and effective method for the treatment of DeBakey type Ⅰ aortic dissection, with satisfactory short-term and long-term efficacy.

Objective:To investigate the bone marrow and peripheral blood cytological characteristics and prognosis in acute myeloid leukemia(AML)with FLT3-ITD mutation.Methods:A total of 106 newly diagnosed AML patients who were hospitalized in the First Affiliated Hospital of Xi'an JiaoTong University from January 2021 to December 2023 were collected,and divided into mutation group and non-mutation group according to the results of high-throughput sequencing of bone marrow specimens.The cytological characteristics of bone marrow smears and peripheral blood smears of patients in the two groups were analyzed at the time of initial diagnosis.The differences in the degree of hyperplasia,the proportion of leukemic cells,and the erythroblasts and megakaryocytes were compared between the two groups.What's more,the relationship between FLT3-ITD mutation status and characteristics of bone marrow and peripheral blood cells was analyzed.Results:AML patients with FLT3-ITD mutation accounted for 24.53％of the hospitalized AML patients during the same period.Patients with peripheral blood leukocyte counts＞30 × 109/L accounted for 53％,and＞100 × 109/L accounted for 15％in FLT3-ITD mutation group.Compared with non-mutation group,the peripheral blood leukocyte count was significantly higher in the mutation group(P＜0.001),and the degree of hemoglobin decline was milder(P＜0.05).The level of platelet was not significantly different between the two groups(P＞0.05).The highest proportion of FAB subtypes were M2a and M5a in mutation group,which accounted for 38％and 27％,respectively.The proportion of extreme hyperplasia of bone marrow in the mutation group was 38.46％,which was higher than 23.75％in the non-mutation group.The proportion of peripheral blood and bone marrow leukemic cells in patients with high-frequency mutation were significantly higher than those in patients with low-frequency mutation(both P＜0.01).The complete remission(CR)rate after the first induction chemotherapy was 38.46％and 65.00％in the mutation group and non-mutation group,respectively,and the CR rate after 2 courses of induction chemotherapy was 50.00％and 73.75％,respectively.Conclusion:The FLT3-ITD mutation results in high proliferation and rapid progression of the bone marrow feature in AML patients,with less suppression of normal erythropoiesis.Increased mutation frequency is accompanied by increased leukemic tumor burden in the bone marrow and circulation,and patients with FLT3-ITD mutation have a low response rate to early induction therapy.

OBJECTIVE: To evaluate the clinical efficacy and safety of Yangxue Qingnao Pills (YXQNP) combined with amlodipine in treating patients with grade 1 hypertension. METHODS: This is a multicenter, randomized, double-blind, and placebo-controlled study. Adult patients with grade 1 hypertension of blood deficiency and Gan (Liver)-yang hyperactivity syndrome were randomly divided into the treatment or the control groups at a 1:1 ratio. The treatment group received YXQNP and amlodipine besylate, while the control group received YXQNP's placebo and amlodipine besylate. The treatment duration lasted for 180 days. Outcomes assessed included changes in blood pressure, Chinese medicine (CM) syndrome scores, symptoms and target organ functions before and after treatment in both groups. Additionally, adverse events, such as nausea, vomiting, rash, itching, and diarrhea, were recorded in both groups. RESULTS: A total of 662 subjects were enrolled, of whom 608 (91.8%) completed the trial (306 in the treatment and 302 in the control groups). After 180 days of treatment, the standard deviations and coefficients of variation of systolic and diastolic blood pressure levels were lower in the treatment group compared with the control group. The improvement rates of dizziness, headache, insomnia, and waist soreness were significantly higher in the treatment group compared with the control group (P<0.05). After 30 days of treatment, the overall therapeutic effects on CM clinical syndromes were significantly increased in the treatment group as compared with the control group (P<0.05). After 180 days of treatment, brachial-ankle pulse wave velocity, ankle brachial index and albumin-to-creatinine ratio were improved in both groups, with no statistically significant differences (P>0.05). No serious treatment-related adverse events occurred during the study period. CONCLUSIONS Combination therapy of YXQNP with amlodipine significantly improved symptoms such as dizziness and headache, reduced blood pressure variability, and showed a trend toward lowering urinary microalbumin in hypertensive patients. These findings suggest that this regimen has good clinical efficacy and safety. (Registration No. ChiCTR1900022470).
Humans ; Amlodipine/adverse effects* ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Hypertension/complications* ; Middle Aged ; Treatment Outcome ; Drug Therapy, Combination ; Adult ; Blood Pressure/drug effects* ; Double-Blind Method ; Aged ; Antihypertensive Agents/adverse effects*

OBJECTIVE: To investigate the effect of zedoarondiol on neovascularization of atherosclerotic (AS) plaque by exosomes experiment. METHODS: ApoE^-/- mice were fed with high-fat diet to establish AS model and treated with high- and low-dose (10, 5 mg/kg daily) of zedoarondiol, respectively. After 14 weeks, the expressions of anti-angiogenic protein thrombospondin 1 (THBS-1) and its receptor CD36 in plaques, as well as platelet activation rate and exosome-derived miR-let-7a were detected. Then, zedoarondiol was used to intervene in platelets in vitro, and miR-let-7a was detected in platelet-derived exosomes (Pexo). Finally, human umbilical vein endothelial cells (HUVECs) were transfected with miR-let-7a mimics and treated with Pexo to observe the effect of miR-let-7a in Pexo on tube formation. RESULTS: Animal experiments showed that after treating with zedoarondiol, the neovascularization density in plaques of AS mice was significantly reduced, THBS-1 and CD36 increased, the platelet activation rate was markedly reduced, and the miR-let-7a level in Pexo was reduced (P<0.01). In vitro experiments, the platelet activation rate and miR-let-7a levels in Pexo were significantly reduced after zedoarondiol's intervention. Cell experiments showed that after Pexo's intervention, the tube length increased, and the transfection of miR-let-7a minics further increased the tube length of cells, while reducing the expressions of THBS-1 and CD36. CONCLUSION Zedoarondiol has the effect of inhibiting neovascularization within plaque in AS mice, and its mechanism may be potentially related to inhibiting platelet activation and reducing the Pexo-derived miRNA-let-7a level.
Animals ; MicroRNAs/genetics* ; Exosomes/drug effects* ; Plaque, Atherosclerotic/genetics* ; Neovascularization, Pathologic/genetics* ; Human Umbilical Vein Endothelial Cells/metabolism* ; Humans ; Blood Platelets/drug effects* ; Apolipoproteins E/deficiency* ; Thrombospondin 1/metabolism* ; CD36 Antigens/metabolism* ; Platelet Activation/drug effects* ; Male ; Mice ; Mice, Inbred C57BL