1.Effects of subanesthetic dose of esketamine on postoperative anxiety and recovery in patients undergoing laparo-scopic cholecystectomy
Zhangzhen ZHONG ; Xian ZHENG ; Ting XU ; Jie WANG ; Hui CAO ; Xinggen ZHOU ; Hui LI ; Jiacheng ZHAO ; Hui LIU ; Chao ZHANG
China Pharmacy 2026;37(2):204-209
OBJECTIVE To investigate the effects of subanesthetic dose of esketamine on postoperative anxiety and recovery in patients undergoing laparoscopic cholecystectomy. METHODS A total of 200 patients scheduled for laparoscopic cholecystectomy at Suzhou Ninth Hospital Affiliated to Soochow University from January 2023 to December 2024 were randomly assigned to control group (n=100) and observation group (n=100). One minute before the initiation of anesthesia, patients in the control group received intravenous injections of Propofol emulsion injection, Sufentanil citrate injection, and Succinylcholine chloride injection. On this basis, patients in the observation group received an intravenous injection of Esketamine hydrochloride injection. The anxiety status of patients in both groups was compared, along with their general intraoperative conditions (including sufentanil dosage, duration of pneumoperitoneum, operative time, anesthesia time, and extubation time), postoperative recovery, incidence of adverse reactions, and the need for dezocine rescue analgesia. Heart rate and mean arterial pressure, entropy index (state entropy and response entropy), inflammatory marker levels [interleukin-6 (IL-6) and C-reactive protein (CRP)], numerical rating scale (NRS) for pain intensity were compared between the two groups at different time points. RESULTS No significant differences were found between the two groups in pneumoperitoneum duration, operative time, anesthesia time,extubation time, incidence of postoperative dry mouth, entropy index or length of stay in the post-anesthesia care unit (P>0.05). Compared with the control group, the observation group showed significantly lower postoperative STAI-S scores, reduced intraoperative sufentanil consumption, decreased incidence of postoperative nausea, vomiting, and shivering, the need for dezocine rescue analgesia, as well as lower plasma IL-6 and CRP levels at 24 h after surgery, and NRS (P<0.05). The heart rate and mean arterial pressure of patients in the observation group at the start of surgery, end of surgery, and during extubation were all significantly higher than those in the control group (P<0.05). CONCLUSIONS Subanesthetic dose of esketamine can effectively alleviate postoperative anxiety, reduce intraoperative opioid consumption, suppress postoperative inflammatory response, relieve postoperative pain, and promote recovery in patients undergoing laparoscopic cholecystectomy.
2.The Neural Circuit Characteristics of Repetitive Transcranial Magnetic Stimulation Over The Dorsolateral Prefrontal Cortex for The Treatment of Migraine
Chen-Xia JIN ; Bo-Lin TAN ; Yang YE ; Ji-Qing HE ; Ling-Yan WANG ; Zhong-Ming GAO ; Yu-Jun WANG ; Hui-Li LIU ; Yong-Xing YAN ; Xian-Wei CHE
Progress in Biochemistry and Biophysics 2026;53(7):1953-1968
ObjectiveMigraine is a leading neurological disorder and the fourth most common cause of years lived with disability worldwide, affecting nearly 116 million individuals. Although pharmacological treatments are available, their efficacy is often limited by side effects and variable response rates. Repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) offers a safe, non-invasive alternative for migraine management. However, the neurophysiological mechanisms, particularly how rTMS modulates local cortical excitability and distributed pain-related circuits, remain poorly understood. Elucidating these mechanisms is essential for optimizing treatment protocols and improving clinical outcomes. MethodsThis study employed concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) to investigate neuroplastic and neurocircuitry mechanisms of DLPFC-rTMS in migraine. Study 1 compared 30 migraineurs and 28 healthy controls to identify abnormalities in TMS-evoked potentials (TEPs) and significant current density (SCD) within sensory-discriminative regions including the primary somatosensory cortex (S1) and posterior insula (pINS), cognitive-affective regions including the anterior insula (aINS) and midcingulate cortex (MCC), and a descending modulatory region, the periaqueductal gray (PAG). Study 2 used a single-blind, crossover, sham-controlled design in 34 healthy participants. Each participant received both active (10 Hz, 80% RMT, 1 500 pulses) and sham DLPFC-rTMS in counterbalanced order. TMS-EEG and cold pain tolerance were assessed before and after each session. ResultsIn Study 1, migraineurs showed a significantly less negative N120 amplitude compared to healthy controls (P=0.027, Cohen’s d=0.60), indicating local intracortical disinhibition. No group differences were observed for N40, P60, or P180 components. At the source level, migraineurs exhibited significantly higher SCD in the S1, pINS, aINS, and MCC (allQ<0.05), but not in the ventroposterior thalamus (vpTHAL), mediodorsal thalamus (mdTHAL), or PAG. In Study 2, active rTMS significantly reduced SCD from pre- to post-stimulation in the S1, aINS, and MCC (all Q<0.05). Sham stimulation also reduced SCD in the S1 (Q<0.05) but not in the aINS or MCC. Although no significant group-level analgesic effect was observed between active and sham conditions (P=0.107), correlation analyses revealed that greater SCD reductions in the S1 and MCC were significantly associated with higher post-rTMS pain tolerance (R=-0.487 and -0.495, both Q<0.01) and larger improvements in pain tolerance(R=-0.487 and -0.451, both Q<0.05). No such correlations were found following sham stimulation, suggesting that the behavioural relevance of neural changes is specific to active rTMS. ConclusionThis study provides novel evidence that migraineurs exhibit both local neuroplastic abnormalities (reduced N120 amplitude) and hyperactivity in key pain-processing regions (S1, pINS, aINS, MCC). A single session of DLPFC-rTMS reduced hyperactivity in the aINS, MCC, and S1. Notably, greater reductions in the S1 and MCC were associated with improved pain tolerance. These findings identify distinct cortical circuitries, particularly within the cognitive-affective pain network, that may serve as potential biomarkers for optimizing rTMS treatment in migraine and other chronic pain conditions. Future studies should validate these results in patient populations experiencing spontaneous migraine attacks and explore multi-session or accelerated rTMS protocols.
3.Individual monitoring results of occupational external exposure for radiation workers in Beijing pet hospital, 2022–2024
Hongfeng ZHAO ; Xian XUE ; Jiejun LI ; Yanhui GAO ; Yaning LIU ; Yiyun WANG ; Yibing TIAN ; Hui XU
Chinese Journal of Radiological Health 2026;35(3):336-342
Objective To analyze personal external exposure dose monitoring results of pet hospital radiation workers in Beijing from 2022 to 2024, and to provide scientific evidence for developing effective monitoring protocols, standardizing radiological practices in pet hospitals, and protecting the health of both workers and the public. Methods Personal dose equivalents, Hp(10), were measured using GR-200A thermoluminescent dosimeters. Monitoring included radiation workers at 286 pet hospitals across all 16 districts of Beijing from 2022 to 2024. Each monitoring cycle lasted no more than 90 days. Annual effective doses were calculated by summing the results of four consecutive quarterly cycles. Data were processed and analyzed using Access and TLPS 6.41 software. All evaluations complied with national laws, regulations, and technical standards. Results A total of 1,579 person-time measurements were recorded. Only 51.87% of workers completed the full four-cycle annual monitoring schedule. Over the study period, the mean annual effective dose was 0.29 mSv, and the median dose was 0.14 mSv. The collective effective dose was 238.34 man-mSv. Notably, 94.26% of workers had annual effective doses below 1.0 mSv, and only 0.12% had doses at or above 5 mSv. Dose levels showed a statistically significant downward trend (P<0.05). Both independent and chain-branded clinics had a median annual effective dose of 0.14 mSv. In independent clinics, the proportion of workers with doses below 1.0 mSv increased from 80.77% in 2022 to 98.82% in 2024. In chain-branded clinics, this proportion rose from 96.88% to 98.11% over the same period. Conclusion Radiation exposure among pet hospital workers in Beijing remains at low levels, well below regulatory limits, and shows an overall declining trend. The disparity in personal doses between independent and chain-branded pet hospitals has diminished over time. Nevertheless, the industry still faces challenges such as high staff turnover and low monitoring completion rates. Expanding monitoring coverage and harmonizing protection standards would provide a scientific basis for precise, nationwide regulation.
4.Pathological Roles and Regulatory Mechanisms of Macrophage Polarization Imbalance in Steroid-associated Osteonecrosis of The Femoral Head
Hui LI ; Duo-Xian WANG ; Wei-Chuang LIU ; Bo-Bo TUO ; Xin CHEN ; Jian-Jun LIU
Progress in Biochemistry and Biophysics 2026;53(9):2392-2401
Steroid-associated osteonecrosis of the femoral head (SANFH) is a progressive osteoarticular disorder associated with prolonged or high-dose glucocorticoid exposure. Its development involves local ischemia, oxidative stress, dysregulated bone metabolism, and disruption of the osteoimmune microenvironment. Macrophages exhibit marked phenotypic plasticity, and their polarization is essential for maintaining the dynamic balance among inflammation, angiogenesis, and bone remodeling. Persistent glucocorticoid stimulation, hypoxia, excessive reactive oxygen species, and damage-associated signals released from necrotic tissues can shift macrophages toward a pro-inflammatory phenotype. Classically activated macrophages (M1 macrophages) predominantly mediate inflammatory responses. By releasing tumor necrosis factor-α, interleukin-1β, interleukin-6, and other mediators, promoting osteoclast activation, suppressing the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), and impairing vascular endothelial function, M1 macrophages accelerate trabecular destruction and expansion of the necrotic lesion. In contrast, alternatively activated macrophages (M2 macrophages) contribute to inflammation resolution, neovascularization, osteogenic repair, and tissue remodeling, thereby supporting regeneration within the necrotic region. Macrophage-derived exosomes further influence disease progression through intercellular communication. Exosomes from different macrophage phenotypes can differentially regulate adipogenic differentiation, neutrophil extracellular trap formation, and endothelial phenotypic transition, thereby affecting the repair capacity of the necrotic area. These findings indicate that macrophage polarization shapes the local microenvironment not only through soluble mediators but also through vesicle-mediated communication with BMSCs, neutrophils, endothelial cells, and other cell populations. At the molecular level, the nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3(NLRP3) inflammasome, nuclear factor kappa B (NF‑κB), Janus kinase/signal transducer and activator of transcription (JAK/STAT), and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathways jointly regulate macrophage polarization and its downstream osteoimmune effects. Dysregulation of these pathways may sustain inflammatory activation, aggravate oxidative and vascular injury, inhibit osteogenesis, and impair tissue repair. NLRP3 inflammasome activation links danger signals and oxidative stress to inflammatory cytokine maturation and pyroptotic injury; NF-κB signaling promotes pro-inflammatory gene transcription and M1 polarization; JAK/STAT signaling participates in the balance between inflammatory and reparative macrophage programs; and PI3K/Akt/mTOR signaling regulates cellular metabolism, survival, autophagy, and regeneration. Notably, the biological effects of PI3K/Akt/mTOR signaling are cell-type dependent, and Akt-mediated repair signaling should be distinguished from mTOR-related autophagy regulation. The pathological significance of macrophage polarization in SANFH is not determined simply by an increase or decrease in a single phenotype. Rather, disease progression appears to result from an imbalance between persistent pro-inflammatory activity and insufficient reparative responses at different stages of the disease. Such an imbalance disrupts the coordinated coupling of inflammation resolution, vascular regeneration, and bone remodeling, ultimately contributing to structural deterioration of the femoral head. This review summarizes the pathological roles, signaling regulation, and exosome-mediated intercellular communication associated with macrophage polarization imbalance in SANFH. A more precise understanding of these mechanisms may clarify the osteoimmune basis of SANFH and support the development of macrophage-targeted interventions. However, most available evidence is derived from cellular and animal studies, and the temporal evolution of macrophage phenotypes in patients remains insufficiently characterized. Therapeutic strategies should therefore move beyond the simple suppression of M1 macrophages or enhancement of M2 macrophages and instead aim to restore a stage-appropriate balance between inflammatory control and tissue repair while promoting angiogenesis and bone reconstruction.
5.Electroacupuncture for hot flashes in early menopause: A randomized sham-controlled trial.
Hui-Xian WANG ; Xin-Tong YU ; Jing HU ; Jin-Jia CHEN ; Yu-Ting MEI ; Yun-Fei CHEN
Journal of Integrative Medicine 2025;23(5):519-527
BACKGROUND:
Electroacupuncture (EA) may affect the severity of hot flashes (HFs) associated with natural menopause and provide additional benefits for postmenopausal women. However, the evidence for its effectiveness in the management of early postmenopausal HFs remains inadequately understood.
OBJECTIVE:
We designed this trial to assess the efficacy and safety of EA for relieving early postmenopausal HFs.
DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS:
This randomized sham-controlled trial involved 72 women with HFs. The participants were divided equally into the intervention and control groups. The intervention group was treated with EA, while the control group was treated with sham acupuncture. The main acupoints used were Hegu (LI4), Guanyuan (RN4), Sanyinjiao (SP6), Taixi (KI3), Fuliu (KI7) and Shenshu (BL23). All participants received 18 treatment sessions, distributed across a 6-week period. The treatment was administered on three occasions per week, adhering to a fixed weekday schedule (Monday, Wednesday, Friday or Tuesday, Thursday, Saturday) with a minimum interval of one day between sessions. Each patient received a 12-week follow-up.
MAIN OUTCOME MEASURES:
The HF score was the primary outcome. Participants documented the frequency and severity of HFs in a 7-day symptom diary, which provided data for calculating the HF score. Secondary outcomes were the Menopause Rating Scale (MRS), Menopause-Specific Quality of Life Questionnaire (MENQOL), Pittsburgh Sleep Quality Index (PSQI) and Traditional Chinese Medicine Syndrome Score Scale (TCMSSS), as well as estradiol (E2), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels.
RESULTS:
Both groups demonstrated significant reductions in HF scores after the treatment and during the follow-up (P < 0.001). Immediately after completion of the 6-week treatment cycle and at 12 weeks post-intervention, the HF scores were similar in both groups. At week 6, the intervention group showed significantly greater improvements in MRS, MENQOL (vasomotor, psychosocial, and physical), PSQI and TCMSSS scores (P < 0.05). The improvements in the MENQOL (vasomotor, and psychosocial) and PSQI total scores persisted through the follow-up (P < 0.05). However, the results showed no significant inter- or intragroup differences in sexual scores on the MENQOL (P > 0.05). EA did not significantly decrease E2, LH or FSH levels compared to placebo. The incidence of adverse events was similar in both groups.
CONCLUSION:
EA does not significantly improve HFs in early postmenopausal patients. However, it enhances the quality of sleep and decreases menopausal symptoms across vasomotor, psychosocial and physical domains.
TRIAL REGISTRATION
Chinese Clinical Trial Registry (http://www.chictr.org.cn); Trial ID: ChiCTR2300072002. Please cite this article as: Wang HX, Yu XT, Hu J, Chen JJ, Mei YT, Chen YF. Electroacupuncture for hot flashes in early menopause: A randomized sham-controlled trial. J Integr Med. 2025; 23(5):519-527.
Humans
;
Female
;
Electroacupuncture
;
Hot Flashes/therapy*
;
Middle Aged
;
Acupuncture Points
;
Quality of Life
;
Menopause
;
Treatment Outcome
;
Adult
6.Application of mindfulness-based stress reduction on the patients treated with image fusion-guided prostate biopsy
Qiang JI ; Jun HU ; Xiao-hong WANG ; Yun LI ; Fan WANG ; Jie LIU ; Hui-xian WEI ; Ying-chun HUANG ; Ying LI
National Journal of Andrology 2025;31(9):812-817
Objective:To evaluate the application effect of mindfulness-based stress reduction(MBSR)therapy on the patients treated with image fusion-guided transperineal prostate biopsy.Methods:A total of 160 patients who underwent image fusion-guided transperineal prostate biopsy in the Urology Department from April 2023 to April 2024 were included.Patients were randomly assigned to a control group and an observation group,with 80 cases in each group.The control group received routine care,while the observa-tion group received combined MBSR on the basis of routine care.The surgical indicators,pain levels,psychological states,nursing satisfaction,and postoperative complication rates of both groups were compared.Results:There was no statistically significant differ-ence in general personal information and clinical data between the two groups(P>0.05).The surgery duration,secondary fusion rate,and postoperative complication rate in the observation group were all lower than those in the control group([23.54±2.07]min vs[26.25±1.69]min,P<0.05;8.75%vs 22.50%,P=0.017;17%vs 29%,P=0.036),and nursing satisfaction was higher in the observation group than in the control group(77%vs 69%,P=0.025).The VAS scores biopsy(5.11±0.93 vs 6.27±1.32,P=0.041),discharge(0.74±0.67 vs 1.85±0.95,P=0.004),and scores of SDS(47.76±2.06 vs 50.46±2.07,P=0.009)and SAS(46.89±2.68 vs 49.75±2.83,P=0.031)in the observation group were all lower than those in the control group.Conclusion:The application of MBSR in image fusion-guided prostate biopsy can synergistically utilize the advantages of minimally in-vasive technology,significantly optimize surgical indicators,and improve patients' psychological experiences,which is worthy of clinical application and promotion.
7.Pathological relationship between circulating tumor DNA and EGFR,KRAS and NRAS mutant resectable non-small cell lung cancer
Lei WANG ; Xian LIU ; Qing-hui WU ; Ke GAO
Journal of Regional Anatomy and Operative Surgery 2025;34(2):154-158
Objective To investigate the relationship between the circulating tumor DNA(ctDNA)and the clinicopathological features of epidermal growth factor receptor gene(EGFR),Kirsten rat sarcoma viral oncogene(KRAS),and neuroblastoma RAS viral oncogene(NRAS)in patients with mutant resectable non-small cell lung cancer(NSCLC).Methods Thirty-six patients with NSCLC who underwent surgical resection in our hospital and had matched plasma samples in the biobank were included for mutation analysis.The EGFR,KRAS and NRAS mutations of plasma ctDNA and biopsy tissue were analyzed by peptide nucleic acid clamp PCR to explore the relationship between plasma ctDNA shedding and clinicopathological features of patients.Results The consistency of EGFR,KRAS and NRAS in biopsy tissue and plasma samples of 36 patients was 63.89%(23/36),88.89%(32/36)and 86.11%(31/36),respectively.In mutant tumors,the sensitivity of EGFR,KRAS and NRAS mutation detection in plasma ctDNA was 23.53%(4/17),33.33%(2/6)and 40.00%(2/5),respectively.In patients with adenocarcinoma,plasma ctDNA shedding was associated with higher tumor stage,N stage,TNM stage,tumor necrosis rate,mitotic count 10HPFs,larger maximum tumor diameter and tumor volume(P<0.05).In subgroup analysis of lung adenocarcinoma patients,ctDNA shedding was significantly associated with higher N stage,vascular invasion rate,tumor necrosis rate,and mitotic count 10HPFs,as well as larger maximum tumor diameter and tumor volume(P<0.05).Conclusion The shedding of ctDNA in lung adenocarcinoma is associated with primary tumor diameter,volume,and aggressive histological features(such as necrosis and high mitotic count).
8.Effect of hospital-family chain rehabilitation management mode on self-management and quality of life in elderly patients with coronary heart disease
Jing WANG ; Chun-xia WANG ; Xing-fang CHEN ; Hui-xian TIAN
Chinese Journal of cardiovascular Rehabilitation Medicine 2025;34(1):129-133
Objective:To investigate effect of hospital-family chain rehabilitation management mode on self-man-agement and quality of life in elderly patients with coronary heart disease(CHD).Methods:This randomized con-trolled study enrolled 220 elderly CHD patients admitted in Hai'an Hospital of Traditional Chinese Medicine between December 2020 and August 2022.They were divided into control group(n=110,routine nursing)and intervention group(n=110,hospital-family chain rehabilitation management mode nursing).After 6-month intervention,scores of Coronary Self-Management Scale(CSMS),China Questionnaire of Quality of life in patients with Cardio-vascular diseases(CQQC)and Perceived Social Support Scale(PSSS)were compared between two groups as well as incidence of adverse cardiovascular events.Pearson method was employed to analyze the association among total scores of CSMS,CQQC and PSSS.Results:After 6-month nursing,compared with patients in control group,those in intervention group had significant higher CSMS total score[(116.03±5.41)points vs.(89.97±4.21)points],CQQC total score[(107.30±6.99)points vs.(80.86±6.38)points],PSSS total score[(69.05±7.42)points vs.(57.05±5.19)points]and each dimensional score(P<0.001 all).Pearson correlation analysis indica-ted that total scores of CSMS,CQQC and PSSS were positively correlated with each other(r=0.437~0.562,P<0.001 all).Incidence of adverse cardiovascular events in intervention group was significantly lower comparing to that of control group(2.73%vs.13.64%,P=0.003).Conclusion:Hospital-family chain rehabilitation manage-ment mode could improve the self-management ability and quality of life,increase the patient's social support,and reduce incidence of adverse cardiovascular events in elderly patients with coronary heart disease.
9.Genetic profiling and intervention strategies for phenylketonuria in Gansu, China: an analysis of 1 159 cases.
Chuan ZHANG ; Pei ZHANG ; Bing-Bo ZHOU ; Xing WANG ; Lei ZHENG ; Xiu-Jing LI ; Jin-Xian GUO ; Pi-Liang CHEN ; Ling HUI ; Zhen-Qiang DA ; You-Sheng YAN
Chinese Journal of Contemporary Pediatrics 2025;27(7):808-814
OBJECTIVES:
To investigate the molecular epidemiology of children with phenylketonuria (PKU) in Gansu, China, providing foundational data for intervention strategies.
METHODS:
A retrospective analysis was conducted on 1 159 PKU families who attended Gansu Provincial Maternity and Child Care Hospital from January 2012 to December 2024. Sanger sequencing, multiplex ligation-dependent probe amplification, whole exome sequencing, and deep intronic variant analysis were used to analyze the PAH gene.
RESULTS:
For the 1 159 children with PKU, 2 295 variants were identified in 2 318 alleles, resulting in a detection rate of 99.01%. The detection rates were 100% (914/914) in 457 classic PKU families, 99.45% (907/912) in 456 mild PKU families, and 96.34% (474/492) in 246 mild hyperphenylalaninemia families. The 2 295 variants detected comprised 208 distinct mutation types, among which c.728G>A (14.95%, 343/2 295) had the highest frequency, followed by c.611A>G (4.88%, 112/2 295) and c.721C>T (4.79%, 110/2 295). The cumulative frequency of the top 23 hotspot variants reached 70.28% (1 613/2 295), and most variant alleles were detected in exon 7 (29.19%, 670/2 295).
CONCLUSIONS
Deep intronic variant analysis of the PAH gene can improve the genetic diagnostic rate of PKU. The development of targeted detection kits for PAH hotspot variants may enable precision screening programs and enhance preventive strategies for PKU.
Humans
;
Phenylketonurias/epidemiology*
;
Female
;
Male
;
Retrospective Studies
;
Phenylalanine Hydroxylase/genetics*
;
Mutation
;
Child, Preschool
;
China/epidemiology*
;
Child
;
Infant
10.Effect of downregulating Hsa-circ-0101216 expression on gemcitabine chemoresistance in pancreatic cancer and its mechanism
Hai-Chao LIU ; Shao-Peng LIU ; Hong-Xian YAN ; Ming-Hui BAI ; Ji-Xiang ZHANG ; Ying-Bo LI ; Chuang WANG ; Kai ZOU
Medical Journal of Chinese People's Liberation Army 2025;50(6):656-664
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.

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