1.Research on Detection Method for Constituent Content of Fresh Tea Leaf Based on Residual Attention Convolutional Neural Network
Hai-Liang ZHANG ; Yan ZHOU ; Wei LUO ; Bai-Shao ZHAN ; Jing ZHANG ; Xue-Mei LIU
Chinese Journal of Analytical Chemistry 2025;53(5):842-851
The rapid and non-destructive detection of constituent content of fresh tea leaves shows an important reference value for quality identification of tea.Visible near infrared(Vis-NIR)spectroscopy has been used for qualitative and quantitative analysis of chemical components in plant samples with the advantages such as simple,rapid and non-destructive detection.In this study,residual attention convolutional neural network(RACNN)was used to predict the internal constituent content of fresh tea leaves.Firstly,the reflectance spectral data of the samples in the Vis-NIR band range and the constituent contents of gallic acid(GA),gallocatechin(GC),epigallocatechin(EGC),and epigallocatechin gallate(ECG)in fresh tea leaves were collected.Based on the preprocessing of the spectral data,the contents of the four components were predicted using a partial least squares regression(PLSR)model,and the optimal preprocessing was determined.Subsequently,the characteristic bands were extracted using the random forest(RF)algorithm.Finally,the performances of PLSR,convolutional neural network(CNN)and RACNN models were compared.The results showed that for GA,the RACNN model worked best with a validation set coefficient of determination(R2)of 0.946 and a root mean square error of the prediction set(RMSEP)of 1.173;for GC,the RACNN model works best with a validation set R2 of 0.928 and RMSEP of 6.081;for EGC,the RACNN model works best with a validation set R2 of 0.891 and a RMSEP of 15.197;for ECG,the RACNN model worked best with a validation set R2 of 0.878 and a RMSEP of 7.837.The RACNN model established by Vis-NIR spectroscopy combined with chemometrics could realize the accurate detection of the contents of components in fresh tea.
2.Sensitive Detection of Nitrofurazone by Electrochemical Sensor Based on Platinum Nanoparticles Functionalized Zeolitic Imidazolate Frameworks-derived Porous Carbon and Carbon Nanotubes
Tong CHANG ; Feng-Lin ZHANG ; Mei-Jie GUO ; Yi-Yan BAI ; Jian-Fang QIN ; Hai-Ying YANG
Chinese Journal of Analytical Chemistry 2025;53(11):1908-1920,中插49-中插52
Nitrofurazone(NFZ)is an antibiotic that is used as a veterinary drug in aquaculture.NFZ abuse can lead to a series of environmental and health issues,making it crucial to establish a rapid and highly sensitive method for NFZ detection.In this study,platinum nanoparticle(PtNPs)-loaded zeolitic imidazolate framework(ZIF-8)was used as a precursor,and PtNPs functionalized nitrogen doped porous carbon(NC)was obtained through pyrolysis.Pt@NC was combined with multi-walled carbon nanotubes(MWCNTs)and cast onto a glassy carbon electrode(GCE)surface to construct an electroch-emical sensor.Electrochemical tests revealed that Pt@NC/WCNT/GCE exhibited an electrochemical active area of 0.066 cm2 and a heterogeneous electron transfer rate constant(k0)of 2.03×10-3 cm/s,which were higher than other materials.Compared with the electrodes modified by other materials,the NFZ generated the highest peak current of irreversible reduction peak on the Pt@NC/WCNT/GCE electrode.In comparison with Pt@ZIF-8/WCNT/GCE,after pyrolysis and carbonization treatment,the reduction current of NFZ increased by 2.19 times,and the reduction peak potential shifted positively by 19 mV simultaneously.When compared with NC/WCNT/GCE,the PtNPs in the composite material enhanced the NFZ current by 4.25 times.Additionally,the experimental conditions for detecting NFZ using the sensor were optimized,including the carbonization temperature of Pt@ZIF-8,ratio of Pt@NC to CNT,loading amount of the modified material,and electrolyte pH.Under the optimized conditions,the sensor demonstrated a linear detection range for NFZ of 0.20-240 μmol/L,a sensitivity of 9.995 μA/((μmol/L)?cm2)and a limit of detection(LOD)of 0.06 μmol/L.The sensor exhibited excellent anti-interference capability,good reproducibility,and stability,with spiked recoveries for NFZ in water samples ranging from 94.6%to 105.6%.This study provided a novel electrochemical sensing approach for NFZ detection.
3.Application of perioperative enhanced recovery after surgery clinical pathway for percutaneous vertebro plasty
Xuehu XIE ; Zhiwu ZHANG ; Jisheng LIN ; Hai MENG ; Tianyu BAI ; Zihan FAN ; Nan SU ; Jiashen SHAO ; Jinjun LI ; Guoyu NI ; Feng JIN ; Yong YANG ; Qi FEI
International Journal of Surgery 2025;52(6):415-422
Objective:To evaluate the perioperative application effect of enhanced recovery after surgery (ERAS) clinical pathway in percutaneous vertebro plasty (PVP).Methods:The clinical data of 274 patients who underwent PVP treatment for osteoporotic vertebral compression fracture (OVCF) in Beijing Friendship Hospital, Capital Medical University from May 2023 to August 2024 were retrospectively analyzed. The patients were divided into two groups according to the different numbers of surgical segments: the single-segment group ( n=211) and the multisegment group ( n=63). Patients in the single-segment group underwent single-segment surgery, while patients in the multisegment group underwent surgery on ≥2 segments. The core points of the ERAS clinical pathway adopted in this study include perioperative education, pain management, early mobilization, application of "outfast", and joint guidance from the departments of nutrition and rehabilitation. Comparison was made between the two groups of patients in terms of visual analog scale (VAS) scores for low back pain at preoperative, 2 h, 6 h, 24 h postoperatively, and on the day of discharge; Oswestry disability index (ODI) scores preoperatively and on the day of discharge; time to first ambulation postoperatively, total length of hospital stay, postoperative length of stay, perioperative complications, and perioperative application of Opioid consumption. Measurement data were expressed as mean±standard deviation ( ± s), and the independent sample t-test was used for comparison between groups; count data were expressed as cases and percentage, and the Chi-square test was used for comparison between groups. The VAS pain scores at each stage of the perioperative period were evaluated using repeated measures analysis of variance or generalized estimating equations. Results:Compared with that before the operation [(6.17±0.93) points, (6.29±0.83) points], the VAS scores of low back pain of patients in the single-segment group and the multisegment group at 2 hours after surgery [(3.09±0.82) points, (3.27±0.65) points], 6 hours after surgery [(2.60±0.79) points, (2.62±0.55) points], and 24 hours after surgery [(1.89±0.77) points, (1.97±0.72) points] and on the day of discharge [(1.72±0.71) points, (1.81±0.64) points] were significantly decreased, and the differences were statistically significant ( P<0.05). At the same stage, the VAS scores of low back pain in both groups were not statistically significant ( P>0.05). The ODI scores of patients in the single-segment group and the multisegment group on the day of discharge [(24.21±2.35) points, (24.63±3.31) points] were significantly lower than those before the operation [(64.50±4.81) points, (65.52±4.08) points], and the differences were statistically significant ( P<0.05). There were no statistically significant differences in perioperative complications and the proportion of Opioid drug application between the two groups of patients ( P>0.05). Conclusion:For patients with single-segment or multisegment OVCF, PVP surgical treatment under ERAS clinical pathway management can achieve immediate pain relief, early ambulation exercise, and satisfactory perioperative efficacy.
4.Investigation on the preoperative nutritional status and analysis of risk factors of patients with osteoporotic vertebral compression fracture based on the MNA-SF scoring tool
Tianyu BAI ; Guoyu NI ; Feng JIN ; Hai MENG ; Jisheng LIN ; Zihan FAN ; Qi FEI
International Journal of Surgery 2025;52(7):456-460
Objective:To evaluate preoperative malnutrition risk in patients with osteoporotic vertebral compression fracture (OVCF) based on mini nutritional assessment short form (MNA-SF) and analyze the related clinical risk factors.Methods:A cross-sectional study was conducted using clinical data from 129 OVCF patients who underwent percutaneous vertebroplasty at Beijing Friendship Hospital, Capital Medical University, between May 2023 and December 2023. The cohort included 26 males and 103 females, aged (74.71±9.13) years(ranging from 48-98 years). According to MNA-SF scoring method, they were divided into three groups, the malnutrition group ( n=6), the nutritional risk group ( n=40), and the good nutrition group ( n=83). Nutritional risk and malnutrition rates were evaluated using the MNA-SF score. Measurement data with normal distribution were expressed as mean±standard deviation ( ± s) and compared using one-way ANOVA. The comparison between groups of count data was conducted using chi-square test. Univariate analysis and multivariate logistic regression were performed to identify independent risk factors for malnutrition and nutritional risk. Results:According to the MNA-SF score, among 129 patients, the malnutrition rate was 4.7%, the nutritional risk rate was 31.0%, and 64.3% exhibited adequate nutrition based on MNA-SF scores. The results of one-way ANOVA showed that gender ( P=0.023) and BMI ( P<0.001) were significantly correlated with malnutrition and nutritional risk; Logistic regression analysis suggested that the influencing factors of nutritional risk included gender ( P=0.002) and BMI ( P<0.001), while the only dangerous factor of malnutrition was BMI ( P<0.001). Conclusions:Bsed on MNA-SF, OVCF patients undergoing percutaneous vertebroplasty have a higher incidence of malnutrition and nutritional risk. The risk factors for nutritional risk in patients are gender and BMI, while the risk factor for malnutrition is only BMI.
5.Antipyretic effects of ethanol extracts of Arisaematis Rhizoma fermented with bile from different sources.
Run ZOU ; Fa-Zhi SU ; En-Lin ZHU ; Chen-Xi BAI ; Yan-Ping SUN ; Hai-Xue KUANG ; Qiu-Hong WANG
China Journal of Chinese Materia Medica 2025;50(7):1781-1791
This study aims to investigate the antipyretic effects and mechanisms of ethanol extracts from Arisaematis Rhizoma fermented with bile from different sources on a rat model of fever induced by a dry-yeast suspension. The rat model of fever was established by subcutaneous injection of 20% dry-yeast suspension into the rat back. The levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6) in the serum, as well as prostaglandin E_2(PGE_2) and cyclic adenosine monophosphate(cAMP) in the hypothalamus, were determined by ELISA. Metabolomics analysis was then performed on serum and hypothalamus samples based on UPLC-Q-TOF MS to explore the potential biomarkers and metabolic pathways. The results showed that the body temperatures of rats significantly rose 4 h after modeling. After oral administration of high-dose ethanol extracts of Arisaematis Rhizoma fermented with bovine bile(NCH) and porcine bile(ZCH), the body temperatures of rats declined(P<0.05), and the NCH group showed better antipyretic effect than the ZCH group. Additionally, compared with the model group, the NCH and ZCH groups showed lowered levels of IL-1β, IL-6, TNF-α, PGE_2, and cAMP(P<0.01). The results of serum and hypothalamus metabolomics analysis indicated that both NCH and ZCH exerted antipyretic effects by regulating phenylalanine metabolism, sphingolipid metabolism, arachidonic acid metabolism, and steroid hormone biosynthesis. Collectively, both NCH and ZCH can play an obvious antipyretic role in the rat model of dry yeast-induced fever, and the underlying mechanism might be closely associated with inhibiting inflammation and regulating metabolic disorders. Moreover, NCH demonstrates better antipyretic effect.
Animals
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Rats
;
Male
;
Fermentation
;
Rats, Sprague-Dawley
;
Rhizome/metabolism*
;
Drugs, Chinese Herbal/chemistry*
;
Bile/chemistry*
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Antipyretics/chemistry*
;
Fever/metabolism*
;
Cattle
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Swine
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Tumor Necrosis Factor-alpha/metabolism*
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Ethanol/chemistry*
;
Interleukin-6/blood*
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Interleukin-1beta/blood*
6.Hypolipidemic effect and mechanism of Arisaema Cum Bile based on gut microbiota and metabolomics.
Peng ZHANG ; Fa-Zhi SU ; En-Lin ZHU ; Chen-Xi BAI ; Bao-Wu ZHANG ; Yan-Ping SUN ; Hai-Xue KUANG ; Qiu-Hong WANG
China Journal of Chinese Materia Medica 2025;50(6):1544-1557
Based on the high-fat diet-induced hyperlipidemia rat model, this study aimed to evaluate the lipid-lowering effect of Arisaema Cum Bile and explore its mechanisms, providing experimental evidence for its clinical application. Biochemical analysis was used to detect serum levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), triglycerides(TG), and total cholesterol(TC) to assess the lipid-lowering activity of Arisaema Cum Bile. Additionally, 16S rDNA sequencing and metabolomics techniques were employed to jointly elucidate the lipid-lowering mechanisms of Arisaema Cum Bile. The experimental results showed that high-dose Arisaema Cum Bile(PBA-H) significantly reduced serum ALT, AST, LDL-C, TG, and TC levels(P<0.01), and significantly increased HDL-C levels(P<0.01). The effect was similar to that of fenofibrate, with no significant difference. Furthermore, Arisaema Cum Bile significantly alleviated hepatocyte ballooning and mitigated fatty degeneration in liver tissues. As indicated by 16S rDNA sequencing results, PBA-H significantly enhanced both alpha and beta diversity of the gut microbiota in the model rats, notably increasing the relative abundance of Akkermansia and Subdoligranulum species(P<0.01). Liver metabolomics analysis revealed that PBA-H primarily regulated pathways involved in arachidonic acid metabolism, vitamin B_6 metabolism, and steroid biosynthesis. In summary, Arisaema Cum Bile significantly improved abnormal blood lipid levels and liver pathology induced by a high-fat diet, regulated hepatic metabolic disorders, and improved the abundance and structural composition of gut microbiota, thereby exerting its lipid-lowering effect. The findings of this study provide experimental evidence for the clinical application of Arisaema Cum Bile and the treatment of hyperlipidemia.
Animals
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Gastrointestinal Microbiome/drug effects*
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Rats
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Male
;
Metabolomics
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Hyperlipidemias/microbiology*
;
Drugs, Chinese Herbal/administration & dosage*
;
Rats, Sprague-Dawley
;
Hypolipidemic Agents/pharmacology*
;
Liver/metabolism*
;
Humans
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Alanine Transaminase/metabolism*
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Triglycerides/metabolism*
;
Aspartate Aminotransferases/metabolism*
7.Clinical study on the efficacy of unicompartmental knee arthroplasty in elderly patients with medial osteoarthritis and anterior cruciate ligament deficiency.
Hai-Song LIANG ; Dong SHENG ; Xiao-Su HUI ; Xin-Wen BAI ; Yu DENG ; Cong-Ke SHU ; Fa-Song XIANG
China Journal of Orthopaedics and Traumatology 2025;38(4):336-342
OBJECTIVE:
To investigate the short-and med-term clinical efficacy of unicompartmental knee arthroplasty(UKA)for the treatment of medial knee osteoarthritis (OA) in elderly patients with anterior cruciate ligament deficiency(ACLD).
METHODS:
A retrospective analysis was conducted on 31 patients aged over 75 years old with primary medial knee OA and ACLD who underwent UKA between January 2018 and December 2022. The cohort included 12 males and 19 females, aged from 75 to 91 years with an average age of (79.56±4.54) years, with 13 left knee, 16 right knee, and 2 bilateral knees. Clinical outcomes were assessed preoperatively and at final follow-up using the visual analogue scale (VAS), Hospital for Special Surgery(HSS) score, range of motion (ROM), hip-knee-ankle angle (HKA), and tibial component posterior slope angle (TCPSA). Complications such as infection, prosthesis wear, prosthesis loosening, and dislocation were also recorded.
RESULTS:
All 31 patients were followed up from 12 to 63 months with an average of (28.34±10.56) months. The average postoperative TCPSA was (4.83±1.31)° ranged from 2.5° to 6.8°. At the final follow-up, there was significant improvement in VAS (3.24±0.53) vs. (6.59±0.69), HSS score (85.19±4.45) vs. (64.38±5.94), ROM (118.83±5.38)° vs. (98.85±4.08)°, and HKA (176.83±5.16)° vs. (169.57±6.28)° compared to preoperative values (P<0.05). No cases of infection, prosthesis loosening, or dislocation were reported.
CONCLUSION
UKA provides favorable short-and mid-term outcomes for elderly patients with medial knee OA and ACLD . However, long-term clinical efficacy needs further investigation through extended follow-up.
Humans
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Male
;
Female
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Arthroplasty, Replacement, Knee/methods*
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Aged
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Osteoarthritis, Knee/physiopathology*
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Retrospective Studies
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Aged, 80 and over
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Range of Motion, Articular
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Anterior Cruciate Ligament Injuries/surgery*
8.Shexiang Tongxin Dropping Pill Improves Stable Angina Patients with Phlegm-Heat and Blood-Stasis Syndrome: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.
Ying-Qiang ZHAO ; Yong-Fa XING ; Ke-Yong ZOU ; Wei-Dong JIANG ; Ting-Hai DU ; Bo CHEN ; Bao-Ping YANG ; Bai-Ming QU ; Li-Yue WANG ; Gui-Hong GONG ; Yan-Ling SUN ; Li-Qi WANG ; Gao-Feng ZHOU ; Yu-Gang DONG ; Min CHEN ; Xue-Juan ZHANG ; Tian-Lun YANG ; Min-Zhou ZHANG ; Ming-Jun ZHAO ; Yue DENG ; Chang-Jiang XIAO ; Lin WANG ; Bao-He WANG
Chinese journal of integrative medicine 2025;31(8):685-693
OBJECTIVE:
To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents.
METHODS:
This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs).
RESULTS:
This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed.
CONCLUSION
STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans
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Double-Blind Method
;
Drugs, Chinese Herbal/adverse effects*
;
Male
;
Female
;
Middle Aged
;
Angina, Stable/physiopathology*
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Aged
;
Syndrome
;
Treatment Outcome
;
Placebos
;
Tablets
9.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.
10.Causal relationship between methylation levels of CpG site in BDNF gene and risk of acute stress disorder:a two-sample Mendelian randomization analysis
Yu-Qing TANG ; Wei XIE ; Hai-Hua BAI ; Rui QIAO
Medical Journal of Chinese People's Liberation Army 2025;50(8):925-934
Objective To investigate the potential association between methylation levels of CpG locus of brain-derived neurotrophic factor(BDNF)gene and risk of acute stress disorder(ASD)[post-traumatic stress disorder(PTSD)or post-traumatic depression].Methods(1)30 specific pathogen-free(SPF)-grade male ICR mice were randomly divided into control group,24 h restraint stress(Res)group,and Res+5-Aza-2'deoxycytidine(Res+5-Aza-cdR)group,with 10 mice in each group.An ASD mouse model was established using 24h restraint stress.The body weight of the mice was recorded daily.At 24 h and 48 h after the successful establishment of the model,open field tests were conducted to evaluate locomotor activity level and anxiety-like behavior of the mice.Reverse transcription-polymerase chain reaction(RT-PCR)and Western blotting were used to detect BDNF mRNA and protein expression levels in the hippocampus of mice in each group.(2)Relevant genome-wide association study(GWAS)summary data were utilized for instrumental variable(IV)selection.A two-sample Mendelian randomization(TSMR)approach was applied to analyze the causal relationship between CpG site methylation of BDNF gene and ASD risk.The leave-one-out method was used to verify the results.Results(1)The results of body weight monitoring and the open field test showed that compared with control group,the body weight,the residence time in the central area,the total movement distance,and the activity times of mice in Res group were significantly decreased(P<0.001).Compared with Res group,the body weight,the residence time in the central area,the total movement distance and activity times of mice in Res+5-Aza group were significantly increased(P<0.00l).The results of RT-qPCR and Western blotting showed that compared with control group,the expression levels of BDNF mRNA and protein in the hippocampus of the mice in Res group were significantly decreased(P<0.05).Compared with Res group,the expression level of BDNF mRNA and protein in Res+5-Aza group was significantly higher(P<0.001).(2)TSMR analysis results showed that the cg10635145 site in BDNF gene(OR=0.862,95%CI 0.793-0.938,P=0.043)was negatively correlated with the risk of PTSD.The cg08362738 site(OR=0.975,95%CI 0.960-0.992,P=0.003)was negatively correlated with the risk of trauma-related depression,whereas the cg18117895 site(OR=1.008,95%CI 1.000-1.016,P=0.047)was positively correlated with the risk of trauma-related depression.The results of Leave-one-out test showed that the causal relationship between the single nucleotide polymorphism(SNP)of CpG site in BDNF gene and ASD was not affected by a strong Ⅳ.Conclusion The CpG loci cg1063145 and cg08362738 of BDNF gene maybe protective factors for ASD-related diseases,while cg18117895 maybe a riskfactor.

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