1.Notoginsenoside R1 modulates mitophagy in human cardiomyocytes viathe Pink1/Parkin pathway after hypoxia/reoxygenation
Xiaoman XIONG ; Huan WU ; Shanglin LU ; Yong WANG ; Yuhua ZHENG ; Yi XIANG ; Haiyan ZHOU ; Xingde LIU
Acta Universitatis Medicinalis Anhui 2026;61(1):53-59
ObjectiveTo investigate the mechanism by which Notoginsenoside R1 (NGR1) ameliorates hypoxia/reoxygenation (H/R)-induced injury in AC16 human cardiomyocyte cell lines through the regulation of mitophagy. MethodsCommon genes linked to hypoxia/reoxygenation injury and mitophagy were identified by intersecting data from GeneCards and MitoCarta databases. AC16 cell viability was assessed via CCK-8 assay under varying NGR1 concentrations (0, 6.25, 12.5, 25, 50, 100, 200, 300, 400, 500 μmol/L). AC16 cells were divided into the following groups: control group (Control), model group (H/R), and treatment groups (H/R + NGR1 at 100, 200 and 300 μmol/L). Mitochondrial membrane potential (ΔΨm) was measured using 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) staining. Transcriptional levels of mitophagy-related genes (Parkin, Pink1, P62) were quantified by reverse transcription-quantitative PCR (RT-qPCR). Protein expression of mitophagy-related markers (Parkin, Pink1, P62, and LC3BⅡ) was evaluated via Western blot analysis. Mitochondrial ultrastructure was visualized by transmission electron microscopy (TEM). ResultsCompared to the control group, cell viability in the H/R group significantly decreased (P<0.01). Treatment with NGR1 at concentrations above 100 μmol/L significantly enhanced the cell viability of AC16 cells compared to the H/R group (P<0.01). H/R induced a significant decrease in mitochondrial membrane potential (P<0.01), which was restored by NGR1 treatment (P<0.01). The mRNA levels of Parkin, Pink1, and P62 in the H/R group were upregulated compared to the control group (P<0.05), while NGR1 intervention downregulated their expression (P<0.05). Protein expression levels of Parkin, Pink1, and LC3BⅡ in the H/R group significantly increased, while P62 expression decreased compared to the control group (P<0.01). In contrast, different doses of NGR1 treatment significantly reduced the expression of Parkin, Pink1, and LC3BⅡ while increasing P62 expression (P<0.05). TEM revealed that the mitochondrial structure in the H/R group was severely disrupted, with fragmented and disorganized cristae, which was alleviated by NGR1. ConclusionNGR1 ameliorates H/R-induced AC16 cell injury, and its mechanism may be associated with modulating the Pink1/Parkin pathway to suppress excessive mitophagy.
2.Compact Fundus Imaging System Using Shack-Hartmann Wavefront Sensing for High-speed Auto-focus
Zhe-Kai LIN ; Long CHEN ; Geng-Yong ZHENG ; Jin-Tian HUANG ; Jia-Xin DONG ; Shang-Pan YANG ; Wen-Zheng DING ; Ding-An HAN ; Xue-Hua WANG ; Ya-Guang ZENG
Progress in Biochemistry and Biophysics 2026;53(4):1076-1086
ObjectiveThe widespread adoption of portable fundus cameras for primary care and community screening is hindered by limitations in current autofocus(AF) technologies. Image-based methods relying on sharpness evaluation require iterative searches, resulting in slow convergence, while projection-based techniques are susceptible to optical artifacts and calibration errors. To address these challenges, this study introduces a novel AF system based on direct wavefront sensing, designed to deliver simultaneous high speed, high precision, and operational robustness within the compact form factor essential for portable ophthalmic devices. MethodsOur approach fundamentally reimagines the AF process by directly measuring the ocular wavefront aberration. We developed a custom portable fundus camera integrating a miniaturized Shack-Hartmann wavefront sensor (SHWS) into the optical path. An 850 nm laser diode projects a point source onto the retina via oblique illumination to minimize corneal reflections. Light scattered from this spot carries the eye’s refractive error through the imaging optics and is directed to the SHWS, positioned at a plane optically conjugate to the primary color CMOS imaging sensor. A microlens array within the SHWS samples the incident wavefront, generating a pattern of focal spots on a CCD. Real-time centroid analysis of these spots provides a map of local wavefront slopes. These measurements are processed through a singular value decomposition (SVD) algorithm to fit a Zernike polynomial basis set, enabling real-time reconstruction of the wavefront phase. The defocus component (S) is extracted from the second-order Zernike coefficients, providing a direct, quantitative measure of the refractive error in diopters. This value serves as a precise error signal in a closed-loop control system, which commands a voice-coil actuated focusing lens to its null position in a single, deterministic step, eliminating the need for iterative search algorithms. ResultsComprehensive evaluation demonstrated the system’s high performance. Testing on a calibrated model eye (OEMI-7) established a highly linear relationship between the computed defocus S and the focusing lens position across a ±20 Diopter (D) compensation range, achievable within a 5 mm mechanical travel. The system achieved a focusing precision of 0.08 D, corresponding to an 18-fold improvement over a conventional projection spot-size method tested under identical conditions. The total focus acquisition time, encompassing wavefront measurement, computation, and lens actuation, averaged under 0.5 s. Clinical validation with 25 human volunteers (50 eyes, refractive range -15 D to +10 D) confirmed practical efficacy. The wavefront-sensing AF succeeded in 92% of attempts with a mean time of 0.5 s, substantially outperforming a projection-based benchmark which achieved only a 32% success rate with an average time of 4.25 s. The system provided instantaneous directional guidance and maintained stability during minor ocular movements. Objective assessment of image quality, via amplitude contrast of retinal vasculature, showed consistent and significant enhancement following AF correction across the entire tested diopter range. ConclusionThis work successfully implements and validates a direct wavefront-sensing autofocus paradigm for portable fundus cameras. By directly quantifying and compensating for the optical defocus aberration, this method bypasses the fundamental limitations of image-processing and projection-based techniques, enabling rapid, precise, and deterministic diopter compensation. The developed system delivers an exceptional combination of a wide operational range (±20 D), high accuracy (0.08 D), fast convergence (0.5 s), and a compact physical footprint. This technology provides a practical and high-performance focusing solution capable of enhancing the reliability, throughput, and diagnostic utility of portable retinal imaging in large-scale screening applications. Future efforts will be directed towards system cost optimization and performance adaptation for diverse ocular conditions.
3.Pre-operative risk assessment of hepatocellular carcinoma recurrence in liver transplant recipients by non-invasive detection of pre-existing genetic lesions
Suqin YANG ; Sunbin LING ; Jianhua LI ; Yan WANG ; Jiapei WANG ; Qiwei HUANG ; Fanming LIU ; Yiqi ZHUANG ; Yingyu ZHENG ; Rui WANG ; Zhe YANG ; Xiaoping ZHENG ; Kai WANG ; Zhikun LIU ; Jun CHEN ; Jianguo WANG ; Haiyang XIE ; Lin ZHOU ; Leiming CHEN ; Guoqiang CAO ; Dandan CHEN ; Junfang JI ; Bin ZHAO ; Chao JIANG ; Di LU ; Xuyong WEI ; Hangjin JIANG ; Qiaonan SHAN ; Hengbo SHI ; Yong-Zhen XU ; Shusen ZHENG ; Zhengxin WANG ; Shengda LIN ; Xiao XU
Clinical and Molecular Hepatology 2026;32(2):884-903
Background/Aims:
Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy.
Methods:
We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues.
Results:
We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts.
Conclusion
Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.
4.Efficacy and Safety of Systemic Thrombolysis in the Treatment of Lower Extremity Fracture Complicated With Distal Deep Vein Thrombosis.
Shi-Qiang LIAO ; Shu-Ming SHI ; Qiang ZHANG ; Chuan-Yong LI ; Guang-Feng ZHENG ; Zhi-Chang PAN ; Jian-Jie RONG
Acta Academiae Medicinae Sinicae 2025;47(2):237-243
Objective To evaluate the efficacy and safety of systemic thrombolysis(ST)and standard anticoagulation(SA)in the treatment of lower extremity fracture complicated with distal deep vein thrombosis(DDVT).Methods We retrospectively analyzed the clinical data of 60 patients with lower extremity fracture complicated with DDVT treated from January 2021 to December 2023.When the lower limb venography indicated a calf thrombus burden score ≥3 points,a retrievable inferior vena cava filter(IVCF)was successfully placed in the healthy femoral vein before orthopedic surgery.The patients who received further anticoagulant or thrombolytic therapy after surgery were allocated into a ST group(n=30,urokinase ST and SA)and a SA group(n=30,only SA).The two groups were compared in terms of calf thrombus burden score,thrombus dissolution rate,IVCF placement time,IVCF retrieval rate,intercepted thrombi,hemoglobin level,platelet count,D-dimer level,and complications.Results There was no statistically significant difference in the calf thrombus burden score between the two groups before treatment(P=0.431).However,after treatment,the scores in both groups decreased(both P<0.001),with the ST group showing lower score than the SA group(P=0.002).The thrombus dissolution rate in the ST group was higher than that in the SA group(P<0.001).There was no statistically significant difference in the IVCF placement time between the two groups(P=0.359),and the IVCF retrieval rate was 100% in both groups.The ST group had fewer intercepted thrombi than the SA group(P=0.002).There was no statistically significant difference in hemoglobin level(P=0.238),platelet count(P=0.914),or D-dimer level(P=0.756)between the two groups before treatment.However,after treatment,both groups showed an increase in platelet count(both P<0.001)and a decrease in D-dimer level(both P<0.001).There was no statistically significant difference in the occurrence of complications between the two groups(P=0.704).Conclusions Both SA and ST demonstrate safety and efficacy in the treatment of lower extremity fractures complicated with DDVT,serving as valuable options for clinical application.Compared with SA,ST not only enhances the thrombus dissolution in the calf but also mitigates the risk of thrombosis associated with IVCF.
Humans
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Venous Thrombosis/therapy*
;
Retrospective Studies
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Thrombolytic Therapy/methods*
;
Male
;
Female
;
Middle Aged
;
Fractures, Bone/complications*
;
Lower Extremity/injuries*
;
Anticoagulants/therapeutic use*
;
Aged
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Treatment Outcome
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Adult
5.Comparison of 24 h Ambulatory Blood Pressure Control Among Hypertensive Patients in Communities in Different Time Periods and Analysis of Its Influencing Factors.
Xiang HUANG ; Hua-Jie YANG ; Yong-Jun ZHENG ; Yu-Ting LI ; Jie-Zhen FENG ; Hao-Xiang WANG ; Ling WANG
Acta Academiae Medicinae Sinicae 2025;47(5):811-821
Objective To assess the blood pressure control and its influencing factors among hypertensive patients in communities in different time periods by 24 h ambulatory blood pressure monitoring(24 h ABPM)and provide reference for optimizing the health management services for hypertension in communities. Methods A total of 765 hypertensive patients registered in the hypertension management project of national essential public health services in Sanxiang Town,Zhongshan City from October 2022 to September 2023 were identified as target subjects.The 24 h ABPM devices were distributed for blood pressure monitoring and a questionnaire survey was conducted to analyze the influencing factors of blood pressure control. Results Of all the participants,16.5% did not monitor blood pressure regularly,and 59.2% monitored blood pressure 1-2 times per week.The patients who were not on night shifts/staying up late had higher mean rates of achieving the target blood pressure and the circadian rhythm of blood pressure during 24 h,nighttime,and early morning than those who were on night shifts/staying up late(all P<0.05).The patients who never drank alcohol had higher rate of achieving the target blood pressure in early morning than those who drank alcohol(P=0.012).The average blood pressure during daytime,nighttime,and 24 h were different by sex(all P<0.05).The average blood pressure during nighttime was different by age and job types(all P<0.05).The average blood pressure during daytime,nighttime,and 24 h were different in patients with different body weight types(all P<0.05).The results of the multivariate logistic regression analysis showed that uncontrolled blood pressure during daytime was more likely to occur in male patients(OR=1.394,95%CI=1.045-1.858,P=0.024),and that during nighttime was more likely to be associated with male patients(OR=1.573,95%CI=1.088-2.275,P=0.016)and night shifts(OR=2.467,95%CI=1.198-5.077,P=0.014).It was difficult to achieve blood pressure control in early morning for the patients who drank alcohol for more than three times per week(OR=4.567,95%CI=1.629-12.807,P=0.004),woke up at night(OR=1.800,95%CI=1.125-2.878,P=0.014),and had night shifts(OR=1.579,95%CI=1.102-2.465,P=0.044).The patients on night shifts were more likely to have abnormal circadian rhythm of blood pressure(OR=1.753,95%CI:1.018-3.018,P=0.043). Conclusions The personal characteristics and lifestyle of hypertensive patients significantly affect the blood pressure control in different time periods(daytime,nighttime,and early morning)and the circadian rhythm of blood pressure.The family doctor team of community healthcare institutions can implement targeted and precise intervention measures for hypertensive patients according to the influencing factors of blood pressure control in different time periods,so as to achieve better management effects.
Humans
;
Blood Pressure Monitoring, Ambulatory
;
Hypertension/physiopathology*
;
Male
;
Female
;
Middle Aged
;
Circadian Rhythm
;
Blood Pressure
;
Surveys and Questionnaires
;
Adult
;
Aged
;
Time Factors
6.Multi-center clinical study on the efficacy and safety of combined lienal polypeptide injection therapy in children with Mycoplasma pneumoniae pneumonia
Qi CHENG ; Yunxiao SHANG ; Han ZHANG ; Jiujun LI ; Ning CHEN ; Lishen SHAN ; Nan YANG ; Lihua NING ; Xuemei BAI ; Jianhua LIU ; Yuling HAN ; Jichun WANG ; Jing LI ; Yong FENG ; Liyun LIU ; Li CHEN ; Si LIU ; Qinzhen ZHANG ; Jia ZHENG ; Fengchao LI ; Sukun LU ; Yun ZHANG ; Xiaoyi CHAI
International Journal of Pediatrics 2025;52(3):204-210
Objective:To observe the efficacy and safety of combined lienal polypeptide injection therapy in the treatment of Mycoplasma pneumoniae pneumonia(MPP)in children aged 3 to 14 years old in multiple clinical centers.Methods:A randomized,controlled,multi-center clinical study design was adopted.A total of 240 hospitalized children aged 3 to 14 years old with MPP from 7 hospitals from September 1,2023 to January 31,2024 were included.According to the severity of pneumonia,they were divided into the mild MPP group with 80 cases and the severe MPP/refractory MPP(SMPP/RMPP)group with 160 cases,and then randomly divided into the control group and the experimental group at a ratio of 1 ∶1,using the random number table method.After screening,subjects entered a treatment period of 5 to 7 days.The control group was treated with azithromycin,while the experimental group was treated with azithromycin plus lienal polypeptide injection .The recovery of lung CT,length of hospital stay,duration of fever,cough score,whether mild cases developed into severe or refractory cases,duration of hormone use,use of intravenous immunoglobulin(IVIG),bronchoscopy treatment,and immune function were observed between the two groups to evaluate the efficacy of lienal polypeptide injection.Adverse events after medication,vital signs,blood routine,urine routine,liver function,myocardial enzymes,renal function,and electrocardiogram were observed to evaluate the safety. Results:A total of 231 subjects have completed the trial in the 7 hospitals,including 118 cases in the experimental group and 113 cases in the control group.Main observation index:the rate of lung CT aggravation in the experimental group was lower than that in the control group(2.6% vs 15.3%, P<0.01),and the difference was statistically significant.Secondary indexes:there were no statistically significant differences in the length of hospital stay,duration of fever,cough score,duration of hormone use,whether IVIG treatment was used,the number of bronchoscopy treatment cases,and immunoglobulin between the two groups(all P>0.05).However,the rate of cases of plastic bronchitis(PB)found under bronchoscopy in the experimental group was lower than that in the control group(0 vs 18.8%, P=0.03),and the difference was statistically significant.Among the mild MPP(72 cases),there were no statistically significant differences in the length of hospital stay,duration of fever,cough score,duration of hormone use,whether IVIG treatment was used,the number of bronchoscopy treatment cases,and the improvement rate of lung CT between the two groups(all P>0.05).However,compared with the control group,the rate of cases developing into SMPP/RMPP in the experimental group was less(24.3% vs 48.6%, P=0.03),and the difference in IgG before and after treatment was small[0.53(-0.04,1.18)g/L vs 1.33(0.48,2.25)g/L, P=0.01].Among the SMPP/RMPP cases(159 cases),the rate of cases of PB found under bronchoscopy in the experimental group was less than that in the control group(0 vs 20%, P=0.04),and the rate of cases with aggravated lung CT in the experimental group was less than that in the control group(1.3% vs 19.5%, P<0.01),and the improvement rate of lung CT in the experimental group was higher than that in the control group(88.8% vs 75.3%, P=0.03),with statistically significant differences.There were no statistically significant differences in the length of hospital stay,duration of fever,cough score,duration of hormone use,whether IVIG treatment was used,the number of bronchoscopy treatment cases,and immunoglobulin between the two groups(all P>0.05).Two cases in the experimental group developed rashes,which improved after the drug was discontinued.There were no serious adverse reactions such as abnormal vital signs like dyspnea and cyanosis due to the use of lienal polypeptide injection.There were no obvious changes in blood routine,liver function,myocardial enzymes,renal function,electrocardiogram,and urine routine values before and after medication compared with the baseline. Conclusion:The combined use of lienal polypeptide injection in the treatment of MPP in children can reduce the probability of the transformation from mild cases to SMPP/RMPP,reduce the rate of aggravation of the image findings,promote the absorption of lung inflammation,reduce the rate of PB found under bronchoscopy,and has good safety.
7.The correlation between the levels of APC,TXB2,and sB7-H3 in peripheral blood of elderly patients with pneumonia and the severity and prognosis of the disease
Fuxia ZHENG ; Lijun MIAO ; Fengxiang HUANG ; Shifu HUANG ; Zengyan GAO ; Ruixia ZHANG ; Yong MENG
The Journal of Practical Medicine 2025;41(7):1056-1061
Objective To investigate the correlation between the levels of activated protein C(APC),thromboxane B2(TXB2),and soluble B7-H3(sB7-H3)in the peripheral blood of elderly patients with pneumonia and the severity as well as prognosis of the disease.Methods One hundred elderly pneumonia patients admitted to our hospital from March 2022 to June 2024 were enrolled as the study group,and 100 healthy volunteers during the same period were selected as the control group.The levels of APC,TXB2,and sB7-H3 in peripheral blood were com-pared between the two groups.Study group patients were further categorized into low-risk,medium-risk,and high-risk subgroups based on the CURB-65 score(Confusion,Uremia,Respiratory rate,Blood pressure,Age≥65 years).The levels of APC,TXB2,and sB7-H3 in peripheral blood were compared among patients with varying disease severities.Pearson correlation analysis was performed to evaluate the correlation between the levels of APC,TXB2,and sB7-H3 in peripheral blood and disease severity.The study group was followed up for 30 days and subsequently divided into good prognosis and poor prognosis subgroups according to their clinical outcomes.Clinical data and peripheral blood levels of APC,TXB2,and sB7-H3 were compared between patients with different prognoses.Partial correlation analysis was conducted to assess the relationship between peripheral blood levels of APC,TXB2,and sB7-H3 and prognosis.Finally,the predictive value of these biomarkers was evaluated using the Receiver Oper-ating Characteristic(ROC)curve.Results The level of APC in the peripheral blood of the study group was signifi-cantly lower than that of the control group,whereas the levels of TXB2 and sB7-H3 were significantly higher(P<0.05).The severity of the disease in the study group was assessed using the CURB-65 score,which categorized patients into 33 mild cases,39 moderate cases,and 28 severe cases.Severe patients exhibited a lower level of APC in peripheral blood compared to moderate and mild patients.Additionally,the levels of TXB2 and sB7-H3 in moderate patients were higher than those in mild patients,while severe patients demonstrated even higher levels of TXB2 and sB7-H3 compared to both moderate and mild patients(P<0.05).Pearson correlation analysis revealed that peripheral blood APC was negatively correlated with the CURB-65 score,whereas TXB2 and sB7-H3 were positively correlated with the CURB-65 score(P<0.05).During a 30-day follow-up period,the research team identified 79 patients with good prognoses and 21 patients with poor prognoses.Significant differences were observed in diabetes prevalence,disease severity,and APACHEⅡ scores between the poor prognosis subgroup and the good prognosis subgroup(P<0.05).The levels of APC in peripheral blood were significantly lower in the poor prognosis subgroup compared to the good prognosis subgroup,whereas the levels of TXB2 and sB7-H3 were significantly higher(P<0.05).Partial correlation analysis revealed that peripheral blood APC,TXB2,and sB7-H3 were significantly associ-ated with prognosis(P<0.05).The AUC values for predicting the prognosis of elderly pneumonia patients using peripheral blood APC,TXB2,and sB7-H3 were 0.752,0.738,and 0.761,respectively,with sensitivities of 66.67%,76.19%,and 66.67%,and specificities of 78.48%,67.09%,and 78.48%.When combining these three indicators for prognostic prediction,the AUC increased to 0.918,with a sensitivity of 85.71%and a specificity of 87.34%,demonstrating a significant improvement in predictive accuracy compared to each indicator used alone(Z=2.207,2.666,2.109,P=0.027,0.008,0.035).Conclusion The levels of APC,TXB2,and sB7-H3 in the peripheral blood of elderly patients with pneumonia are significantly associated with the severity and prognosis of the disease.Combined detection of these biomarkers can serve as a reliable predictor of clinical outcomes.
8.Effects of high-altitude hypoxia exposure on brain injury in rats based on oxidative stress and aquaporins
Xin-jue ZHANG ; Wang-jie CAO ; Yun SU ; Hong-xia GONG ; Yong HUANG ; Yong-qi LIU ; Jian-zheng HE ; Jia-wang GUO ; Neng-xian ZHANG
The Chinese Journal of Clinical Pharmacology 2025;41(1):81-85
Objective To explore the brain damage of SD rats under different time points of hypobaric hypoxia exposure.Methods A rat high-altitube cerebral edema(HACE)model was constructed by simulating an altitude of 6 000 m in a hypobaric hypoxia animal experimental chamber.Thirty-six SD male rats were randomly divided into the control group and the hypobaric hypoxia exposure 3,7 and 14 d groups,with 9 rats in each group.Except for the control group,the rats in each group were continuously exposed to hypobaric hypoxia for 3,7,and 14 d.At the end of the modeling period,serum was collected by blood sampling via the abdominal aorta,and brain tissue samples were taken.The wet-to-dry ratio(W/D)of brain tissue was calculated,and the levels of relevant oxidative enzymes in serum and brain tissue were measured.The expression levels of hypoxia-inducible factor-1α(HIF-1α)and aquaporin 4(AQP4)mRNAs in brain tissue were detected by real-time fluorescence quantitative polymerase chain reaction.Results The W/D of brain tissues in the control group and the group exposed to hypobaric hypoxia for 3,7 and 14 d were 4.46±0.12,4.98±0.16,5.07±0.18 and 4.95±0.07;the superoxide dismutase contents were(111.86±2.45),(90.73±1.48),(79.64±2.56)and(55.33±1.45)U·g-1;the glutathione contents were(126.91±5.18),(125.26±1.53),(56.20±2.17)and(122.73±1.78)μg·mL-1;the malondialdehyde contents were(230.94±2.00),(362.65±3.28),(407.34±3.47)and(237.50±1.59)nmol·g-1;the relative expression levels of HIF-1 α mRNA were 1.00±0,2.99±0.49,4.72±0.49 and 1.91±0.28;the relative expression levels of AQP4 mRNA were 1.00±0,2.62±0.34,8.38±0.84 and 5.27±0.42,respectively.Statistically significant differences were found between the above indexes in the 3,7 and 14 d of hypobaric hypoxia exposure group compared with the control group(P<0.05,P<0.01).Conclusion Different time of hypobaric hypoxia exposure can up-regulate the expression of AQPs proteins in HACE rats and cause the disruption of the blood-brain barrier,and the HACE model constructed in the hypobaric hypoxia chamber with 6 000 m intervention for 7 d was more stable.
9.Eplerenone alleviates rheumatoid arthritis in mice by inhibiting macrophage M1 polarization through Kv1.3/Bcl-2/NF-κB pathway
Chi XIAO ; Jing CAI ; Zi-hang WANG ; Yong-zheng ZHANG ; Jing YANG ; Lu-feng CHENG
Chinese Pharmacological Bulletin 2025;41(4):726-737
Aim To investigate the effect of eplerenone(EPL)on the alleviation of rheumatoid arthritis(RA)based on voltage-gated potassium channel 1.3(Kv1.3)/B-cell lymphoma-2(Bcl-2)/nuclear factor-κB(NF-κB)to inhibit macrophage M1 polarization in mice.Methods Bioinformatics technology was used to screen disease pathways and targets,and the binding affinity and stability of EPL-Kv1.3 complex system were calculated.A mouse model of RA was established and treated with EPL by intragastric administration for 42 days.The indicators reflecting drug remission of RA were recorded and detected.RAW264.7 cells were treated with EPL to detect the indicators reflecting the effect of drugs on macrophage M1 polarization,and to verify the upstream and downstream key targets of re-lated signaling pathways mediated by drugs.Results Bioinformatics analysis showed that the disease targets were mainly involved in inflammatory response and NF-κB signaling pathway,and EPL-Kv1.3 had high affinity and stable binding.In animal experiments,the detec-tion of anti-cyclic citrullinated peptide antibody(CCP-Ab)and joint score indicated the successful establish-ment of the model.Compared with the model group,EPL could reduce the toe redness and swelling score,alleviate the plantar redness and swelling,synovial swelling,and reduce fibrosis and inflammatory cell in-filtration in mice.The medium-dose and high-dose EPL groups reduced the HE staining score(P<0.05,P<0.01),and the high-dose EPL group reduced the serum RF in mice(P<0.01).CCK-8 results showed that low,medium and high doses of EPL had no effect on the activity of RAW264.7 macrophages(P>0.05).Compared with the model group,EPL treatment significantly reduced the contents of IL-6,TNF-α and NO in supernatant of the cells(P<0.01),reduced the nuclear translocation of NF-KB-p65 in the high-dose EPL group,reduced the M1 polarization and increased the proportion of M2 polarization in the medium and high-dose EPL groups(P<0.01).The mRNA levels of MyD88,IκB-α,NF-κB-p65,NF-KB-p50,IL-1 β and iNOS were significantly reduced in each dose group of EPL(P<0.01).EPL significantly increased the pro-tein expression of Bcl-2(P<0.01)and decreased the protein expression of Kv1.3,MyD88,p-IκB-α/IκB-α,p-p65/p65,IL-1 β and iNOS(P<0.05).Conclusion EPL may play an immunomodulatory role in relieving RA in mice by regulating Kv1.3/Bcl-2/NF-κB path-way,reducing macrophage M1 polarization and amelio-rating macrophage-associated inflammatory response.
10.Cost-effectiveness of PD-L1 testing to guide immunotherapy for patients with non-small cell lung cancer in China
Yuan LI ; Lingchuan GUO ; Yong YUAN ; Qiang ZHENG ; Yan JIN ; Jian MING
China Oncology 2025;35(2):237-248
Background and purpose:According to the latest data from the National Cancer Center,the incidence rate and mortality of lung cancer in China rank first among all malignant tumors,and 85%are non-small cell lung cancer(NSCLC).In recent years,immunotherapy based on programmed cell death protein-1(PD-1)/programmed death ligand-1(PD-L1)immune checkpoint inhibitors(ICIs)has made breakthrough progress in lung cancer,bringing more survival benefits to lung cancer patients.This study aimed to evaluate the cost-effectiveness of three major PD-L1 testing assays in guiding immunotherapy for patients with NSCLC,and to provide empirical evidence to guide the selection of cost-effective diagnosis and ICIs monotherapy regimens for NSCLC patients in China.Methods:From a healthcare system perspective,a decision-tree model was constructed to simulate the cost and effectiveness(percentage of the patients who were successfully diagnosed and who were correctly prescribed and underwent correct treatment according to China treatment guidelines)of employing Ventana PD-L1 IHC(SP263)assay,PD-L1 IHC 22C3 pharmDx,and Dako 22C3 antibody concentrate in early to mid-stage and advanced NSCLC patients in China,respectively.The cost-effectiveness of SP263 assay compared to other testing methods was assessed through the incremental analysis.The robustness of the base case analysis results was validated by using one-way sensitivity analysis and probabilistic sensitivity analysis.Results:When considering atezolizumab monotherapy following chemotherapy for early to mid-stage(Ⅱ A-Ⅲ B)NSCLC patients,in comparison to the 22C3 assay or 22C3 antibody concentrate,the SP263 assay incurred an additional cost of 9 449 yuan per successfully diagnosed and treated patient.The SP263 assay,which can guide multiple ICIs monotherapies(e.g.,atezolizumab,pembrolizumab)for advanced(Ⅳ)NSCLC patients,was dominant by achieving a higher percentage of successfully diagnosed and treated patients at a lower cost compared to Dako 22C3 assay and Dako 22C3 antibody concentrate.One-way sensitivity analysis and probabilistic sensitivity analysis both confirmed the robustness of the results.Conclusion:The Ventana PD-L1 IHC SP263 assay was cost-effective,compared to Dako PD-L1 IHC 22C3 assay and Dako 22C3 antibody concentrate for the immunotherapy treatment for both stage Ⅱ A-Ⅲ B and stage Ⅳ NSCLC patients in China.

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