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10 December 2024, Volume 40 Issue 23
Basic Research
The effect of melatonin on the maturation level of oocytes and mitochondrial dynamics in mice exposed to benzophenone⁃3
Ruojin SHI,Yuying XIONG,Xueling ZHANG,Long JIN,Haiying. ZHU
2024, 40(23):  3275-3283.  doi:10.3969/j.issn.1006-5725.2024.23.001
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Objective To investigate the effects and mechanisms of melatonin (MT) on improving oocyte quality in mice exposed to benzophenone-3 (BP-3). Methods In this study, 6 ~ 12-week-old female ICR mice were cultured in vitro in M16 culture, 0.8 μmol/L BP-3 medium and 1 × 10-7 mol/L MT + 0.8 μmol/L BP-3 mixed culture. Female ICR mice were randomly segregated into three groups: control, BP-3, and BMT. The control group received 0.5 mL of purified water, the BP-3 group was administered 0.5 mL of a 0.8 μmol/L BP-3 solution, and the BMT group received 0.5 ml of a combination of 0.8 μmol/L BP-3 and 15 mg/kg MT solution via gavage once daily for four weeks, to facilitate in vivo experimentation. Subsequently, the oocyte maturity rate, transcription levels and protein expression levels of mitochondrial dynamics-related genes Mfn1, Opa1, Fis1 and Drp1, mitochondrial membrane potential and spindle morphology were detected in the three groups to explore the rescue effect of MT on the mitochondria of BP-3-exposed mice. Results Compared to the control group, MT treatment markedly enhanced the transcription and protein levels of the mitochondrial fusion genes Mfn1 and Opa1 in oocytes, while concurrently down-regulating the mRNA and protein levels of the mitochondrial fission genes Fis1 and Drp1. Additionally, the BMT group exhibited significantly lower levels of ROS and abnormal spindle morphology in their oocytes compared to the BP-3 group, yet their mitochondrial membrane potential was notably elevated. Conclusion Physiological concentration of BP-3 exposure was toxic for reproduction, but the addition of appropriate concentrations of MT could significantly improve the mitochondrial dynamics and developmental potential of oocytes in BP-3-exposed mice.

Effect of mangiferin on differentiation of bone marrow mesenchymal stem cells induced by homocysteine
Suzhen CHAO,Nian ZHOU,Xinyi SHI,Yili ZHOU,Junjie XIA,Bo LIU,Mingshi REN,Zihan. LI
2024, 40(23):  3284-3290.  doi:10.3969/j.issn.1006-5725.2024.23.002
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Objective To establish a lipid differentiation model of primary rat bone marrow mesenchymal stem cells (rBMSCs) in vitro using homocysteine (Hcy), and analyze the specific effects of Hcy on lipid and bone differentiation of BMSCs; to comprehensively explore the effects of mangiferin on lipid and bone differentiation of BMSCs, and further reveal the potential mechanism of mangiferin in the treatment of osteoporosis through the intervention of Hcy-induced BMSCs by different concentrations of mangiferin. Methods First, rBMSCs were extracted and isolated. The rBMSCs that were well-cultured to a certain generation were placed in culture medium containing different concentrations of Hcy (0.125, 0.250, 0.5, 1, 2, 4 mmol/L) to establish lipid differentiation model of rBMSCs. Then, different concentrations of mangiferin (37.5, 75, 150 μmol/L) were applied to the experimental cells for intervention. After culture for a certain period of time, the cells were collected for the following tests: The accumulation of lipids in the cells was detected by semi-quantitative method of oil red O dye solution to evaluate the degree of lipid differentiation; The activity of alkaline phosphatase (ALP) was measured by ρNPP method; The expression of bone morphogenetic protein-2 (BMP-2) and type I collagen (ColⅠ) were detected by western blot assay to evaluate the degree of bone differentiation. Results Mangiferin could significantly up-regulate the expression of BMP-2 and ColⅠ in vitro, increase the level of ALP, and promote bone differentiation of rBMSCs. Hcy promoted lipid differentiation of rBMSCs by increasing lipid accumulation, and down-regulated the expression of BMP-2 and ColⅠ, reduced the intracellular ALP level, thereby inhibiting bone differentiation of rBMSCs. However, the above Hcy-related effects could be successfully reversed by mangiferin. Conclusion Mangiferin can significantly promote bone differentiation of rBMSCs in vitro, while Hcy can inhibit bone differentiation of rBMSCs and promote its lipid differentiation. Mangiferin has the ability to reverse this effect, indicating that mangiferin has certain potential in the treatment of osteoporosis-related diseases.

The inhibitory effect and molecular mechanism of 6-gingerol on human multiple myeloma cells
Chunfang KONG,Anna LI,Bo KE,Weirong DING,Tingting LIU,Huan FU,Tingting ZHANG,Chenghao JIN,Mei. WU
2024, 40(23):  3291-3297.  doi:10.3969/j.issn.1006-5725.2024.23.003
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Objective To investigate the inhibitory effect and elucidate the molecular mechanism of 6?gingerol on human multiple myeloma cells. Methods The human multiple myeloma cell lines RPMI 8226 and ARH77 were cultured in vitro, followed by treatment with varying concentrations (50, 100, 200, 300, 400 μmol/L) of 6?gingerol. The inhibitory effect on cell proliferation was assessed using the CCK?8 assay. Flow cytometry was employed to evaluate cell apoptosis and cycle distribution. Additionally, qRT?PCR and Western blotting techniques were utilized to analyze gene and protein expression levels. Results The proliferation of RPMI 8226 and ARH77 cells was dose? and time?dependently inhibited by 6?gingerol, leading to the induction of apoptosis with statistically significant differences (P < 0.05). Further mechanistic investigations revealed that treatment with 6?gingerol arrested RPMI 8226 cells in the G0/G1 phase, resulting in a significant increase in Bax levels and a decrease in Bcl?2 mRNA and c?Myc mRNA levels (P < 0.05). Additionally, it significantly upregulated the expression of Bax, Cleaved?PARP, Cleaved?caspase3, P53, and p?AKT proteins while down regulating the expression of Bcl?2 protein (P < 0.05). Conclusions The compound 6?Gingerol exhibits inhibitory effects on the proliferation and induction of apoptosis in MM cells, as well as cell cycle arrest at the G0/G1 phase. Its mechanism of action is likely associated with the suppression of the AKT signaling pathway, downregulation of Bcl?2 family protein expression, and inhibition of c?Myc expression.

Type Ⅱ alveolar epithelial cell⁃derived exosomal miR⁃21⁃5p targeting SKP2 alleviate bronchopulmonary dysplasia
Yan JIANG,Xiaoqin WANG,Hong MEI,Xinxin LIU,Zhenliang LIAO,Kun YU,Banghai FENG,Song QIN
2024, 40(23):  3298-3305.  doi:10.3969/j.issn.1006-5725.2024.23.004
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Objective To investigate the impact of exosomal (Exos)-miR-21-5p (miR-21) targeting S-phase kinase associated protein 2 (SKP2) derived from Type Ⅱ alveolar epithelial cells (AEC?Ⅱ) on the pathogenesis of bronchopulmonary dysplasia (BPD). Methods A total of 60 SD rats aged 6 ~ 8 weeks were utilized in this study, with 30 of them subjected to extraction and culture through differential adherent centrifugation. Density gradient centrifugation was employed for the isolation of AEC?Ⅱ derived exosomes, while vesicles from AEC?Ⅱ medium were extracted using density gradient centrifugation. These isolates were subsequently confirmed by transmission electron microscopy and particle size analysis, and the targeting relationship between miR-21 and SKP2 was validated through dual-fluorescein reporter gene assay. The remaining 30 mice were combined in a male-to-female ratio of 3∶1 to facilitate pregnancy testing. These neonatal mice were randomly assigned into four experimental groups: air control group (Con group), hyperoxia group (BPD + PBS group), hyperoxia-treated mice receiving exosomes (BPD + Exos-miR-21 group), and hyperoxia combined with exosome miR-21 inhibitor treatment group (BPD + Exos-AV-miR-21 group). Neonatal SD rats will be exposed to 85% oxygen to establish a BPD model. Following 14 days of high oxygen treatment, the expression levels of miR-21 in lung tissues and exosomes will be assessed using RT-qPCR. HE staining will be employed to observe pathological changes in lung tissue, while mean alveolar linear intercept (MLI) and radial alveolar count (RAC) will be calculated. Superoxide dismutase (SOD), malondialdehyde (MDA), and total antioxidant capacity (T-AOC) levels will be determined spectrophotometrically, whereas reactive oxygen species (ROS) levels will be measured via fluorescence spectrophotometry. Additionally, Western blot analysis will assess the expression levels of SKP2, NR2F2, and VEGF-A proteins. Results The results obtained from electron microscopy and particle size analysis demonstrated that the vesicle structure isolated from AEC?Ⅱ cells corresponded to exosomes. Moreover, there was a significant upregulation of miR-21 expression in exosomes (P < 0.01). Subsequently, the dual luciferase gene reporter assay confirmed SKP2 as the target of miR-21. Comparative analysis revealed that compared to the Con group, both BPD + PBS and BPD + Exos-AV-miR-21 groups exhibited disordered lung tissue structure with enlarged and simplified alveoli, increased levels of ROS, MDA, and MLI along with elevated expression of SKP2 protein (P < 0.01). Conversely, RAC, SOD, T-AOC levels were downregulated alongside miR-21 expression while NR2F2 and VEGF-A protein expressions decreased significantly (P < 0.01). In contrast to the BPD+PBS group, the number of alveoli without alveoli increased in the BPD+Exos-miR-21 group leading to improved degree of alveolar simplification accompanied by reduced MLI, ROS, MDA levels as well as decreased SKP2 protein expression (P < 0.01). Additionally ROC,SOD,T-AOC,and miR-21 expressions were upregulated while NR2F2and VEGF-A expressions were increased(P < 0.01). Conclusions The exosomal miR-21 derived from AEC?Ⅱ may potentially target SKP2, thereby inhibiting oxidative stress and promoting alveolar development. Consequently, it can improve BPD by enhancing the protein expression of NR2F2 and VEGF-A.

Metformin exerts a protective effect on articular cartilage in osteoarthritis rats by activating the SIRT1/p53 signaling pathway
Xiang JIA,Tianjie XU,Jiaxin FAN,Xiaoling GUO,Kainan LIU,Hui ZHANG,Yongsheng WANG,Qian. WANG
2024, 40(23):  3306-3316.  doi:10.3969/j.issn.1006-5725.2024.23.005
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Objective To investigate the underlying mechanism of metformin's protective effect on articular cartilage in rats afflicted with osteoarthritis. Methods Thirty male SD rats were randomly divided into three groups (n = 10 per group) to establish a rat model of knee osteoarthritis. The metformin group received metformin via gavage [200 mg/(kg·d)], while the control and model groups received saline as a control. After 4 weeks, morphological staining was used to observe articular cartilage morphology, and immunohistochemical staining, immunofluorescence staining, and Western blot were employed to detect the expression of factors related to the SIRT1/p53 signaling pathway, inflammation, and apoptosis. Results Compared to the model group, the metformin group exhibited significantly reduced cartilage structural damage, characterized by a smoother cartilage surface, increased chondrocyte population, and enhanced proteoglycan content. Immunohistochemical staining, immunofluorescence staining, and Western blot analysis revealed significantly higher expression levels of SOX9, Aggrecan, Bcl?2, and SIRT1 proteins in the metformin?treated cartilage tissue compared to the model group. Conversely, lower expression levels of IL?6 TNF?α BAX Caspase?9 and p53 proteins were observed in the metformin group compared to the model group. TUNEL staining results demonstrated a significant reduction in apoptotic chondrocytes within the metformin?treated group when compared with the model group. Conclusion Metformin exerts a protective effect on articular cartilage in SD rat models of osteoarthritis by activating the SIRT1/p53 signaling pathway, leading to decreased chondrocyte apoptosis and inhibition of extracellular matrix degradation.

Clinical Research
Effect of different methods of hemodynamic support for patients with cardiac shock complicating acute myocardial infarctionduring percutaneous coronary intervention process
Minghua LUO,Yushan CHEN,He WANG,Huaimin GUAN,Jinhong. XIE
2024, 40(23):  3317-3322.  doi:10.3969/j.issn.1006-5725.2024.23.006
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Objective To evaluate the effect of extracorporeal membrane oxygenation combined with intra-aortic balloon pump mechanical circulatory support for patients with cardiogenic shock complicating acute myocardial infarction during PCI process. Methods Patients with cardiogenic shock complicating myocardial infarction who underwent PCI in the hospital from January 2015 to December 2019 were selected. Those who were under support of extracorporeal membrane oxygenation combined with intra-aortic balloon pump were enrolled in the observation group, the patients under support of only intra-aortic balloon pump were selectedin the control group. The differences of clinical features and prognosis were compared. Results A total of 40 patients were enrolled, 11 were in the observation group and 29 in the control group. Compared with control group, more patients were complicated with old myocardial infarction (5/11 vs. 2/29, P = 0.016), more patients were diagnosed as non-ST elevated myocardial infarction (8/11 vs. 11/29, P = 0.049) and left ventricular ejecting fraction was lower [(38.5 ± 10.10) vs. (48.55 ± 8.86), P = 0.01] in observation group. Moreover, the proportion of patients with EF < 35% was higher in the observation group (5/11 vs. 3/29, P = 0.01). The observation group has significantly higher rates of multi-vessel disease and Syntax scores compared to the control group (multi-vessel disease: 10/11 vs. 11/29, P = 0.02; Syntax score: [(33.36 ± 13.37) vs. (25.74 ± 5.75), P = 0.015]; the observation group exhibited a higher proportion of patients achieving complete revascularization(9/11 vs. 8/29,P = 0.002). Mechanical complications were higher in observation group(6/11 vs. 5/29, P = 0.02), The survive rate in observation group is higher than that in control group(91.00% vs.55.17%, P = 0.03)at one-year follow-up. Conclusion Compared with only IABP, ECMO combined with IABP hemodynamic support during PCI process for patients with cardiogenic shock complicating acute myocardial infarction enjoys more complete revascularization and better mortality outcome, although it has relatively higher mechanical complications.

The relationship between AGI event grading and short⁃term prognosis in patients with acute ischemic stroke of different severity levels
Shaohui LIU,Xi WU,Siyuan WEI,Zhixin WU,Shaojuan HUANG,Yi SU,Yuanyi LI,Wending FAN,Qingyu. WU
2024, 40(23):  3323-3330.  doi:10.3969/j.issn.1006-5725.2024.23.007
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Objective To explore the grading of acute gastrointestinal injury (AGI) events in patients with different severities of acute ischemic stroke (AIS) and correlation of short-term prognosis. Methods AIS patients admitted from the Advanced Stroke Center of the Eighth Clinical Medical College of Guangzhou University of Chinese Medicine from January 2023 to November 2023 were retrospectively selected, and depending on the degree of nerve function defect (NIHSS) scores. AIS patients were divided into two groups: NIHSS ≤ 14 group and NIHSS > 14 group.The National Institute of Health Stroke Scale (NIHSS) score, general baseline data, clinical test indicators, AGI event classification and short-term prognosis were collected at admission. Results A total of 270 patients were included, with an average age of (64.95 ± 13.65) years, 70.0% males and 30.0% females. The proportion of AIS patients with AGI incident accounted for 66.30%. AIS patients after AGI incidents, 90 days after the onset of the modified Rankin rating scale (mRS) score > 2 points of 83 people, accounting for 30.7%; The poor clinical outcomes of 270 AIS patients with different AGI event grades were significantly different (P < 0.05), among which AGI grade 0 and AGI gradeⅠwere significantly different from AGI grade Ⅲand AGI grade Ⅳ, respectively. The incidence of poor prognosis of AGI grade Ⅲ and AGI grade Ⅳ is significantly higher than that of AGI grade 0 and AGI grade Ⅰ. In AIS patients with NIHSS > 14 group, there were significant differences in the adverse clinical outcomes between AGI grade 0, AGI gradeⅠand AGI grade Ⅲ (P < 0.05), and the incidence of poor prognosis of AGI grade Ⅲ was significantly higher than that of AGI grade 0 and AGI gradeⅠ. Multivariate Logistic regression analysis showed that NIHSS score was an independent risk factor for AGI events in AIS patients (P < 0.05). The higher the NIHSS score, the higher the risk of AGI events in AIS patients. And age, NIHSS score, systolic blood pressure is 90 days after AGI events affect AIS patients independent risk factors of poor prognosis (P < 0.05), the higher the age, the greater the NIHSS score, the higher systolic blood pressure of patients with AIS 90 days after AGI events are at higher risk of poor prognosis. Conclusion AGI event grading in patients with AIS of different severity is associated with short-term prognosis.

Predictive value of Cys C, HMGB1, GDF-15 levels for early infection after flap reconstruction for diabetic foot ulcer
Hongtao FENG,Xiaoping JIAO,Wenxuan SHANG,Hongpu. LI
2024, 40(23):  3331-3336.  doi:10.3969/j.issn.1006-5725.2024.23.008
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Objective To explore the predictive value of cystatin C (Cys C), high mobility group box 1 (HMGB1), and growth differentiation factor?15 (GDF?15) levels for early infection after flap reconstruction for diabetic foot ulcer (DFU). Methods From July 2021 to March 2024, 155 DFU patients treated in our hospital were included in DFU group. DFU patients were assigned into non?infection group (104 cases) and infection group (51 cases) according to whether there was infection at the operation site within one week after flap reconstruction. Control group included 85 patients with diabetes but without foot ulcer. Latex immunoturbidimetry was applied to detect serum Cys C level; enzyme linked immunosorbent assay to detect serum levels of HMGB1 and GDF?15;multivariate logistic regression to analyze the factors affecting early infection after flap reconstructionfor DFU, and receiver operating characteristic (ROC) curve to analyze the predictive value of serum Cys C, HMGB1, and GDF?15 levels for early infection after flap reconstruction for DFU. Results The expression levels of serum Cys C, HMGB1, and GDF?15 were obviously higher in the DFU group (P < 0.05) when compared with those in the control group. The expression levels of FPG, CRP, Cys C, HMGB1, and GDF?15 were obviously higher in the infection group (P < 0.05) when compared with those in the non?infection group. Cys C, HMGB1, GDF?15, FPG, and CRP were all independent risk factors for early infection after flap reconstruction for DFU (P < 0.05). The AUC predicted by serum Cys C, HMGB1, and GDF?15 alone for early infection after flap reconstruction for DFU was 0.810, 0.850, and 0.828, respectively. The AUC predicted by the combination of these three markers was 0.930, which was better than that predicted by the three markers alone (ZCys C?three combination = 3.381, ZHMGB1?three combination = 2.588, ZGDF?15?three combination = 2.857, all P < 0.05). Conclusions Cys C, HMGB1, and GDF-15 are upregulated in the serum of DFU patients, and all the three are factors affecting early infection after flap reconstruction for DFU. The combination of the three has high predictive value for early infection after DFU flap repair.

Analysis of the effects of different personalized cutting modes of SPT⁃Trans PRK on visual quality and corneal higher order aberrations after myopic astigmatism surgery
Yu FENG,Xin LI,Zhenjia ZHANG,Xinping JIA,Qingxin. ZHAO
2024, 40(23):  3337-3342.  doi:10.3969/j.issn.1006-5725.2024.23.009
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Objective To investigate and analyze the impact of three personalized surgical design schemes for SPT trans PRK on postoperative visual quality and higher-order aberrations in individuals with myopic astigmatism, aiming to provide a foundation for more rational selection of personalized design schemes. Methods The 96 cases (96 eyes) with myopic astigmatism were divided into three groups based on three personalized design schemes and a conventional mode. Specifically, 24 eyes were assigned to the personalized group 1, which focused on coma elimination; another 24 eyes belonged to personalized group 2, where the aim was to minimize spherical aberration elimination; and the remaining 24 eyes were further categorized into personalized group 3 based on a model that aimed at minimizing spherical aberration. Additionally, there were also 24 eyes in the control group treated using the conventional mode. The study compared and analyzed various parameters including best corrected visual acuity, spherical aberration, coma, total higher-order aberration of the anterior corneal surface, as well as differences in corneal ablation thickness between personalized and conventional schemes within the surgical design software. Results (1) The postoperative visual acuity of the personalized group was significantly superior to that of the control group (P < 0.05); (2) Among the personalized groups, Group 2 exhibited a reduced amount of corneal tissue ablation compared to other groups (P < 0.01); (3) Group 2 demonstrated lower values than the other groups after surgery (P < 0.05). (4) Coma: The control group showed a significantly higher level of coma compared to preoperative measurements (P < 0.01). No significant differences were observed between Groups 1, 2, and 3 after surgery (P > 0.05). (5) Total higher-order aberrations: All groups experienced a significant increase in total higher-order aberrations following surgery (P < 0.01). Group 2 exhibited lower values than the other groups postoperatively (P < 0.05). Conclusion For myopic astigmatism, SPT trans PRK incorporates the personalized surgical scheme with a focus on minimizing spherical aberration elimination mode, resulting in enhanced optimization of postoperative high-order aberration and improved visual quality, while preserving corneal tissue.

Relationship between changes of serum neurotransmitters and stress hormones and secondary brain injury during acute cerebral hemorrhage
Han XU,Yue LU,Pu. YUAN
2024, 40(23):  3343-3348.  doi:10.3969/j.issn.1006-5725.2024.23.010
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Objective To investigate the relationship between the changes of serum neurotransmitters and stress hormones and secondary brain injury (SBI) in acute stage of cerebral hemorrhage. Methods The data of 149 patients with intracerebral hemorrhage admitted to the hospital from January 2020 to December 2023 were retrospectively analyzed. The patients with intracerebral hemorrhage who developed SBI 5 days after treatment were divided into the group with SBI and the group without SBI. Serum neurotransmitters and stress hormones were measured before treatment and 3 days after treatment. The levels of serum neurotransmitters and stress hormones in patients with and without SBI were compared, the factors affecting the occurrence of SBI were analyzed, and the value of serum neurotransmitters and stress hormones in predicting the occurrence of SBI in patients with cerebral hemorrhage was analyzed. Results Logistic regression analysis showed acute physiological and chronic health status score Ⅱ, cerebral hemorrhage volume, gamma-aminobutyric acid (GABA) level and adrenocorticotropin releasing hormone (CRH) were the factors affecting the complication of SBI in patients with cerebral hemorrhage (P < 0.05). ROC curve analysis results showed that the sensitivity of GABA, CRH and their combined prediction of SBI in patients with cerebral hemorrhage were 68.29%, 70.73% and 85.37%, the specificity was 70.37%, 72.22% and 89.81%, and the AUC was 0.708 (95%CI: 0.604 ~ 0.813), 0.711 (95%CI: 0.597 ~ 0.825), 0.882 (95%CI: 0.812 ~ 0.951). Conclusion Serum neurotransmitter GABA and stress hormone CRH are related to the complication of SBI in patients with cerebral hemorrhage, and the combination of GABA and CRH is effective in predicting the complication of SBI in patients with cerebral hemorrhage.

Logistic regression versus CART decision tree model for predicting pulmonary infection in elderly patients with heart failure with reduced left ventricular ejection fraction
Min LI,Hongqiang ZHAO,Bin CAO,Lili LIU,Yuzhen BAO,Fengyong. YANG
2024, 40(23):  3349-3355.  doi:10.3969/j.issn.1006-5725.2024.23.011
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Objective To analyze the risk factors of pulmonary infection in elderly patients with heart failure with reduced left ventricular ejection fraction heart failure, and establish a risk predicting model of pulmonary infection in those patients by decision tree CART algorithm. Methods 320 elderly patients with heart failure with reduced left ventricular ejection fraction admitted from January 2020 to December 2022 were retrospectively selected as study objects, and were divided into an infection group and a non-infection group according to whether the patients were complicated with pulmonary infection. Logistic regression model and decision tree CART model were used to construct a prediction model of heart failure with reduced left ventricular ejection fraction complicated with pulmonary infection, and 5-fold cross-validation method was used for internal verification. The prediction efficiency of the models was compared. Results In the 320 patients, the incidence of pulmonary infection was 30.94%. The data on age, smoking history, diabetes mellitus, cardiac function grades, COPD, invasive procedures, length of hospital stay were compared between the infection and non-infection groups (P < 0.05). logistic regression analysis showed that age of ≥ 75 years smoking history, complications with diabetes or/and COPD, cardiac function grade Ⅲ/Ⅳ, invasive procedures, and hospital stay of ≥14 days were independent risk factors for pulmonary infection in the patients (P < 0.05). Probability forecasting model P = 1/[1 + e(-3.368+0.763*X1+0.814*X2+0.652*X3+1.085*X4+0.865*X5+1.027*X6+0.652*X7)], with an overall accurate rate of prediction of 80.9%. The Omnibus test showed P < 0.001. The accuracy of prediction was 73.6% after the cross-validation of 5 fold. The decision tree model showed that invasive procedures were the most important influencing factors for pulmonary infection in elderly patients with heart failure with reduced left ventricular ejection fraction, with an information gain of 0.280. The ROC showed that the AUC value of logistic regression model was slightly higher than that of the decision tree (Z = 2.850, P = 0.004), and the prediction efficiency of both models was medium. Conclusions Age, smoking history, complications with diabetes mellitus or/and COPD, cardiac function grades, invasive procedures, and length of hospital stay are all influencing factors for pulmonary infection in elderly patients with heart failure with reduced left ventricular ejection fraction. The decision tree model constructed in this study has a better efficiency for risk prediction, and it can provide reference for early clinical screening and intervention of heart failure with reduced left ventricular ejection fraction.

Predictive efficacy of free mitochondrial DNA and miR⁃146a expression in peripheral blood in assessing short term prognosis of sepsis
Haiyan WU,Baoyu WANG,Baohui JIA
2024, 40(23):  3356-3361.  doi:10.3969/j.issn.1006-5725.2024.23.012
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Objective To explore the value of free mitochondrial deoxyribonucleic acid (DNA) and micro ribonucleic acid (miRNA, miR)?146a expression in peripheral blood in assessing short?term prognosis of sepsis. Methods Totally 145 patients with sepsis admitted to the hospital from March 2021 to February 2023 were selected to detect the free mitochondrial DNA and miR?146a expression in peripheral blood. The incidence of poor prognosis after 28 days was counted, and the patients were then divided into poor prognosis group and good prognosis group. The general data and the free mitochondrial DNA and miR?146a expression in peripheral blood of the two groups were compared. Logistic regression analysis was used to explore the influencing factors of poor prognosis in patients. Receiver operating characteristic (ROC) curve was drawn to analyze the predictive efficacy of free mitochondrial DNA and miR?146a expressionin assessing the short?term prognosis of sepsis. Results The incidence of poor short?term prognosis in the 139 patients who completed the study was 28.78%. Concurrent diabetes (OR = 1.765, 95%CI:1.181 ~ 2.637), acutephysiology and chronic health evaluation (APACHE Ⅱ) score (OR = 1.972, 95%CI:1.317 ~ 2.953), free mitochondrial DNA in peripheral blood (OR = 2.416, 95%CI:1.524 ~ 3.829), and miR?146a expression (OR = 2.462, 95%CI:1.431 ~ 4.237) were risk factors for poor short?term prognosis of patients with sepsis (P < 0.05). The sensitivity, specificity and area under curve (AUC) of free mitochondrial DNA and miR?146a expression in peripheral blood to predict poor short?term prognosis were higher than those of APACHE Ⅱ score (P < 0.05), and the sensitivity and AUC of free mitochondrial DNA and miR?146a expressions in peripheral blood to predict poor short?term prognosis were higher than those of both alone (P < 0.05). Conclusions Free mitochondrial DNA and miR?146a expression in peripheral blood are related to poor short?term prognosis of sepsis. The efficacy of both of them in assessing poor short?term prognosis of sepsis is better than that of APACHE Ⅱ score, and their combined prediction efficacy is even better.

Drugs and Clinic Practice
Effect of tiopronin on renal function during antituberculosis therapy
Lixiu LIU,Guofeng LI,Honglan ZHONG,Huaying HUANG,Xiuzhen WEN,Xiang. LI
2024, 40(23):  3362-3366.  doi:10.3969/j.issn.1006-5725.2024.23.013
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Objective To investigate the effect of tiopronin on renal function during anti?tuberculosis liver protection therapy. Methods Clinical data of patients with initially treated sensitive tuberculosis treated in our hospital from September 2019 to September 2022 and whose anti?tuberculosis regimen was only isoniazid, rifampicin, pyrazinamide and ethambutol were retrospectively analyzed. The patients were divided into study group and control group according to whether tiopronin was used. The baseline data, blood creatinine (Scr), blood urea nitrogen (BUN), urine protein, creatinine clearance, drug combination and related adverse reactions of the two groups were compared. Results Patients obtained based on inclusion and exclusion criteria were divided into a study group (n = 102) (antitubercular drugs + tiopronin) and a control group (n = 105) (antitubercular drugs + glutathione). There were no statistically significant differences (P > 0.05) in ALT, AST, DBIL, and TBIL levels between the two groups before treatment, at Middle and late treatment. At the later stage of treatment, serum Scr, BUN, creatinine clearance and urinary protein showed statistical differences between the study group and the control group (P < 0.05). The abnormal rate of indicators and the incidence of adverse reactions in the study group were higher than those in the control group at the later stage of treatment (P < 0.05). Conclusion For patients undergoing tuberculosis treatment, the efficacy of tiopronin and glutathione in protecting the liver is comparable. However, in terms of renal function, long?term use of tiopronin is associated with more pronounced damage. Due to the relatively low cost of tiopronin, for families with heavy economic burdens, short?term use of the drug can ensure safety, while long?term use requires close monitoring of renal function changes and timely adjustments to medication.

Medical Examination and Clinical Diagnosis
Correlation between the ratio of tumor volume to uterine volume and the expression of Ki⁃67 and p16 protein in tissues with the pathological features and recurrence of endometrial carcinoma
Liping CHEN,Juyu LUO,Zhangyan PENG,Xiulan WU,Yuhong YANG,Lianyan SHI,Xiaoyun LI,Ling. WANG
2024, 40(23):  3367-3372.  doi:10.3969/j.issn.1006-5725.2024.23.014
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Objective To investigate the correlation between the ratio of lesion volume to uterine volume (T/U), the expression levels of Ki-67 and p16 proteins in lesion tissue, and the recurrence risk of endometrial cancer. Methods A total of 150 patients diagnosed with endometrial carcinoma through pathological examination at Qiandongnan Prefecture People's Hospital were enrolled for follow-up observation. Among them, 28 patients experienced recurrence after a 2-year follow-up period, while 122 patients remained recurrence-free. The expression differences of Ki-67 protein and p16 protein in T/U and lesion tissues during surgery were compared between the two groups. Furthermore, these indexes were analyzed based on different pathological features, and the variation in relapse-free survival time was assessed among patients with distinct T/U status as well as Ki-67 and p16 protein expressions. Results The T/U value and the positive expression rate of Ki-67 protein were significantly higher in the relapsed group compared to the non-relapsed group, while the positive expression rate of p16 protein was significantly lower in the relapsed group (P < 0.05). Additionally, patients with T/U ≥ 0.18 had a significantly higher proportion of stage Ⅲ patients and patients with low histological differentiation compared to those with T/U < 0.18 (P < 0.05). Furthermore, patients with positive expression of Ki-67 protein exhibited a significantly higher proportion of stage Ⅲ patients, patients with low histological differentiation, and lymph node metastasis compared to those with negative expression of Ki-67 protein (P < 0.05). The proportion of stage Ⅲ patients exhibiting positive p16 protein expression, low histological differentiation, and lymph node metastasis was significantly lower compared to those with negative p16 protein expression (P < 0.05). Patients with endometrial cancer having a T/U ≥ 0.18 experienced shorter recurrence-free survival time 2 years post-surgery in comparison to patients with T/U < 0.18 (χ2 = 6.962, P = 0.008). Patients displaying positive Ki-67 expression had a shorter recurrence-free survival time 2 years after surgery than those with negative Ki-67 expression (χ2 = 4.815, P = 0.028). The recurrence-free survival time 2 years after surgery for patients expressing p16 protein positively was longer than that for patients expressing it negatively (χ2 = 4.279, P = 0.039). The presence of FIGO stage Ⅲ, lymph node metastasis, depth of myographic invasion ≥1/2, T/U value ≥ 0.18, and positive expression of Ki-67 protein were identified as significant risk factors for postoperative recurrence in endometrial cancer (P < 0.05). Conversely, the positive expression of p16 protein was found to be a protective factor against recurrence in endometrial carcinoma following surgery (P < 0.05). Conclusion The expression of T/U, Ki-67 protein, and p16 protein in endometrial cancer patients is associated with tumor progression and may augment the risk of postoperative recurrence.

Correlation of high signal intensity of infrapatellar fat pad on symptoms and structure of knee osteoarthritis
Yuke SONG,Jinfan XU,Xiaoming HE,Tianye LIN,Mincong HE,Qiushi. WEI
2024, 40(23):  3373-3378.  doi:10.3969/j.issn.1006-5725.2024.23.015
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Objective To analyze the correlation between high signal intensity of infrapatellar fat pad (IPFP) and symptoms and structural changes of osteoarthritis of the knee in patients with osteoarthritis of the knee based on image digitization. Methods Imaging and clinical data of patients with knee osteoarthritis (KOA) were retrospectively analyzed. The differences in knee osteoarthritis symptoms and structural changes in patients with different IPFP high signal intensities were compared, and the relationship between IPFP high signal intensity changes and knee osteoarthritis symptoms as well as structural changes was also analyzed. Results A total of 219 patients (268 knees) were collected and completed imaging measurements and evaluations, and the median IPFP high signal intensity (27.40%) was used to compare the groups. The IPFP high signal intensity ≥ 27.40% group had a significantly higher degree of tibial cartilage damage, changes in knee angle, pain, and total scores on the osteoarthritis index (western ontario and mcMaster). universities osteoarthritis index (WOMAC) were significantly higher than those in the IPFP high signal intensity < 27.40% group, with a statistically significant difference (P < 0.05); IPFPF high signal intensity changes were associated with knee pain, joint line convergence angle, JLCA, and knee joint angle. Angle (JLCA), knee kellgren?Lawrence (KL) classification, and the degree of femoral and tibial cartilage damage were significantly positively correlated (P < 0.05). Conclusion In patients with KOA, there is a significant correlation between IPFP high signal intensity changes and knee pain symptoms as well as structural changes, which may be an important factor influencing the progression of KOA.

Modernization of Traditional Chinese Medicine
Clinical study on myofascial release for the treatment of upper limb spastic paralysis after stroke
Yangting LÜ,Yiwen. YIN
2024, 40(23):  3379-3383.  doi:10.3969/j.issn.1006-5725.2024.23.016
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Objective To investigate the clinical efficacy of myofascial release in the management of upper limb spastic paralysis after stroke (SPAS) and its impact on the central nervous system. Methods The patients with upper limb spasticity who visited Second Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine from January 2023 to March 2024 were randomly divided into a control group (n = 50) receiving conventional treatment and acupuncture, and a treatment group (n = 50) receiving conventional treatment and myofascial release. The clinical response rate was assessed by comparing the modified Ashworth Spasticity Scale (MAS) scores between the two groups. Additionally, changes in simplified Fugl-Meyer Assessment (FMA) scores, electromyographic F-waves, and serum gamma-aminobutyric acid (GABA) levels were compared. Results The total effective rate of the treatment group was 96%, while that of the control group was 86%, showing no statistically significant difference (P = 0.08). However, the effective rate in the treatment group was significantly higher than that in the control group (P < 0.05). Following treatment, both groups exhibited a significant reduction in MAS scores (P < 0.001), with a notably greater decrease observed in the observation group compared to the control group (P < 0.05). Moreover, after treatment, there was a significant increase in FMA scores for both groups (P < 0.05), and this increase was significantly more pronounced in the observation group than in the control group (P < 0.05). After treatment, both groups exhibited a significant reduction in electromyographic F-waves amplitude and a significant increase in threshold (P < 0.05). Moreover, the observation group demonstrated a significantly greater degree of change compared to the control group (P < 0.05). Following treatment, serum GABA levels significantly decreased in both groups (P < 0.001), with the observation group showing a markedly higher decrease than the control group (P < 0.001). Conclusion In comparison to conventional acupuncture, myofascial release demonstrates superior efficacy in improving muscle tension and limb motor function for the treatment of upper limb SPAS, while also facilitating central nervous system regulation.

Clinical Nursing
Impacts of cognitive behavioral therapy based on 5G internet of things on rehabilitation and kinesiophobia in elderly patients with coronary artery diseasefollowing PCI
Jie LI,Nian DENG,Guofeng SHI,Tao XU,Li YANG,Yu ZHANG,Yueyue SONG,Yuanzhu LIAO,Yixia. ZHOU
2024, 40(23):  3384-3388.  doi:10.3969/j.issn.1006-5725.2024.23.017
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Objective To explore the effects of cognitive behavioral therapy based on 5G internet of things (IOT) on rehabilitation and kinesiophobia in elderly patients after percutaneous coronary intervention (PCI) for coronary artery disease. Methods Sixty elderly postoperative PCI patients with coronary artery disease admitted from June to December 2023 were selected as study subjects and randomly divided into the control group and the 5G group, with 30 cases in each group.The control groupreceived conventional nursing intervention, while the 5G group receivedcognitive behavioral therapy based on 5G IOT in addition to traditional nursing. Left ventricular ejection fraction (LVEF), 6-minute walking distance (6MWD), the Tampa Scale for kinesiophobia Heart (TSK-SV Heart) scores, the Seattle Angina Questionnaire (SAQ) scores, and rehabilitation compliance were compared between the two groups. Results 12 weeks afterintervention, LVEF and 6MWD in the 5G groupwere significantly improved as compared with those in the control group (P < 0.05). The TSK-SV Heart scores in the 5G group werelower than those in the control group (P < 0.05),but the SAQ scores were higher (P < 0.05). And the rate of better rehabilitation compliance in the 5G group was significantly higher than thatin the control group (P < 0.05). Conclusions Cognitive behavioral therapy based on 5G IOT helps to improve the rehabilitation effect in elderly patients with coronary artery disease after PCI, reduce kinesiophobia, improve quality of life, and enhance rehabilitationcompliance, thus promoting the rehabilitation process of the patients.

Reviews
Research progress on the treatment of osteoarthritis with small molecules derived from traditional Chinese medicine:A review of literatures
Gang DENG,Lixin ZHU,Jiasong GUO,Yizhou. XU
2024, 40(23):  3389-3393.  doi:10.3969/j.issn.1006-5725.2024.23.018
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Osteoarthritis (OA) is a prevalent chronic degenerative disease in clinical practice, posing significant health threats while lacking specific effective treatments. In recent years, an increasing number of small molecules derived from traditional Chinese medicine have been utilized in experimental studies and clinical treatment of OA. The utilization of these small molecules aligns to a certain extent with traditional Chinese medical theories related to OA treatment. Moreover, due to their well?defined chemical structures and the reproducibility of their effects, along with relatively well?understood mechanisms, these compounds are gaining growing attention in the fields of OA research and clinical practice. To advance this field's development, this article systematically reviews the therapeutic efficacy and underlying mechanisms of various small molecules used for treating OA including curcumin, atractylenolide, resveratrol etc., aiming to provide relevant background information and insights for researchers and clinicians.

Advances in the role and mechanism of ISG15 in malignant tumours of the gastrointestinal tract
Ping JIANG,Xiaoqin LUO,Shaoqian ZHAI,Chengzhu CAO,Zhanhai. SU
2024, 40(23):  3394-3404.  doi:10.3969/j.issn.1006-5725.2024.23.019
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Interferon?stimulating gene 15 (ISG15), an ubiquitin?like molecule belonging to the superfamily of ubiquitin?like proteins, is highly expressed in various malignant tumors and induced by type I interferon. However, its specific regulatory mechanism remains unclear. Numerous studies have demonstrated its close association with tumorigenesis and development. In this study, we provide a comprehensive review on the role of ISG15 protein in hepatocellular carcinoma, esophageal carcinoma, gastric carcinoma, colorectal carcinoma, and other cancers. Our aim is to identify new therapeutic targets for gastrointestinal malignancies and improve prognostic assessment.

The pathogenetic diagnostic techniques and research progress in patients with fever of unknown origin
Xiaoyan SONG,Ruishan WU,Wenzhong ZHAO
2024, 40(23):  3405-3410.  doi:10.3969/j.issn.1006-5725.2024.23.020
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Fever is a common pathophysiological response of the body to foreign pathogens or substances, and it is also one of the most important clinical manifestations in the progression of diseases. The diagnosis of fever of unknown origin (FUO) is a clinical challenge, and infectious diseases (ID) are among the most common causes of FUO. Through diagnostic techniques in microbiology, the occurrence and nature of infections can be rapidly determined. The latest diagnostic technologies have accelerated the identification of pathogenic microorganisms and antimicrobial susceptibility analysis, enabling early disease assessment, precise treatment, and facilitating the rapid recovery of patients. This article reviews the causes of FUO, infectious diseases that cause fever, microbiological diagnostic methods, and research progress, aiming to provide reference for the accurate and rapid diagnosis of FUO.

Research progress on chorioamnionitis and related neonatal diseases
Binghui LI,Qiong MENG
2024, 40(23):  3411-3418.  doi:10.3969/j.issn.1006-5725.2024.23.021
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Chorioamnionitis (CAM) refers to an inflammatory condition resulting from pathogen infection of the chorion, amnion, and decidua of the placenta. CAM is associated with preterm birth and an increased risk of adverse outcomes in neonates, including respiratory distress syndrome, bronchopulmonary dysplasia, and elevated perinatal mortality rates. Therefore, early identification, diagnosis, and treatment of CAM are crucial for optimizing therapeutic success in pregnant women and newborns while enhancing the quality of life and disease prognosis for neonates. This review aims to elucidate the correlation between CAM and neonatal diseases as well as provide insights into current prevention strategies and treatment approaches to offer novel clinical perspectives for improved management of CAM?related newborns.

Dual role and new strategies of pyroptosis in cancer therapy
Xiao XIAO,Fangyi LONG,Gang. WANG
2024, 40(23):  3419-3426.  doi:10.3969/j.issn.1006-5725.2024.23.022
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Pyroptosis is a form of programmed cell death with inflammatory characteristics, which has attracted wide attention in the biomedical field in recent years. Pyroptosis plays a crucial role in activating host defenses, promoting inflammatory responses, regulating immune responses, and influencing the tumor microenvironment. In cancer research, the dual role of pyroptosis is particularly significant, which can both inhibit tumor growth and promote tumor development in certain instances. Furthermore, research on pyroptosis offers new perspectives for cancer treatment, particularly in enhancing the efficacy of traditional chemoradiotherapy, boosting anti-tumor immune responses, and applying nanotherapeutic strategies. This article reviews the regulatory role of pyroptosis in cancer progression, as well as its theoretical basis and practical applications as a potential anti-cancer strategy, with the aim of providing new insights and directions for the development of cancer treatment strategies in the future.