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25 January 2025, Volume 41 Issue 2
Basic Research
The effect of remimazolam on modulating the ROS/RAGE/NF-κB signaling pathway in LPS-induced microglial inflammation
Xingwei WU,Jianying WANG,Chengxiao GUO,Ziyi LIU,Chao SUN,Fei. YU
2025, 41(2):  153-161.  doi:10.3969/j.issn.1006-5725.2025.02.001
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Objective To investigate the anti?inflammatory protective effects of remimazolam on microglial cells and elucidates the potential molecular mechanisms underlying these effects. Methods The mouse microglial cell line (BV2) was selected as the research object. The following groups were set up: the control group (complete medium), the Rema group (200 μg/mL remimazolam), the model group (1 μg/mL lipopolysaccharide, LPS), and different?concentration administration groups (1 μg/mL LPS + 50, 100, 200 μg/mL remimazolam). In the Rema group, cells were treated with 200 μg/mL remimazolam alone for 26 h. In the model group, cells were treated with LPS for 24 h. In the different?concentration administration groups, cells were pre?treated with different concentrations of remimazolam for 2 h, and then treated with LPS for 24 h. The effects of LPS and remimazolam on the morphology of BV2 cells were observed and evaluated using an optical microscope. Cell viability was determined using the CCK?8 assay, while the expression and secretion of inflammatory cytokines were quantified by quantitative real?time PCR and ELISA. Reactive oxygen species (ROS) levels were measured using a fluorescent probe. Additionally, malondialdehyde (MDA) content, superoxide dismutase (SOD) activity, and glutathione peroxidase (GSH) activity were evaluated using respective assay kits. Western blot analysis was conducted to examine the protein expression levels of Bax, Bcl?2, IL?1β, RAGE, NF?κB, p?NF?κB, IκBα, p?IκBα, iNOS, and Arg?1. Immunofluorescence staining was employed to visualize NF?κB nuclear translocation and M1/M2 polarization in the cells. Results Compared to the control group, LPS?treated BV2 cells demonstrated significantly reduced cell viability, elevated expression and secretion of inflammatory cytokines (TNF?α, IL?6, IL?1β), decreased activities of SOD and GSH, and increased intracellular levels of MDA and ROS. Additionally, RAGE protein levels were upregulated, along with enhanced phosphorylation of IκBα and NF?κB, leading to observable NF?κB nuclear translocation. The expression of the M1 marker iNOS was upregulated, while that of the M2 marker Arg?1 was downregulated. In contrast, in the LPS+Rema group, cell viability was restored, expression and secretion of inflammatory cytokines were attenuated, SOD and GSH activities were improved, and levels of MDA and ROS were reduced compared to the LPS group. Furthermore, RAGE protein expression and phosphorylation levels of IκBα and NF?κB were diminished, inhibiting NF?κB nuclear translocation. The expression of the M1 marker iNOS was downregulated, while that of the M2 marker Arg?1 was upregulated. Conclusion Remimazolam mitigates LPS?induced inflammation by facilitating the transition of microglial cells from the M1 to the M2 phenotype via modulation of the NF?κB pathway and reduction of ROS production.

Gypenosides LI down⁃regulates CPT1B through the pathway of lipid metabolism to inhibit the growth of colon cancer
Wenyu ZHU,Hongwei ZHANG,Decai TANG,Fangyuan CHEN,Hua JIANG,Haiyan MIN,Jie. DING
2025, 41(2):  162-169.  doi:10.3969/j.issn.1006-5725.2025.02.002
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Objective To elucidate the mechanism through which Gypenoside L inhibits the growth of colon cancer by modulating carnitine palmitoyltransferase 1B (CPT1B), a pivotal enzyme in the fatty acid metabolism pathway. Methods Through in vitro experiments, various concentrations of Gypenoside LI LI were applied to intervene in colon cancer RKO and SW620 cells. The effects of Gypenoside LI on these cells were comprehensively evaluated using the CCK?8 assay, wound healing assay, colony formation assay, and live?dead cell staining, focusing on its impact on cell proliferation, migration, and apoptosis. Additionally, a human colon cancer tissue microarray (TMA) was utilized in conjunction with multiplex fluorescence immunohistochemistry to analyze the expression of CPT1B in colon cancer and adjacent tissues. SW620 cells were transfected with siRNA, and the mRNA and protein expression levels of CPT1B post?transfection were assessed using quantitative real?time PCR (qPCR) and Western blotting. Furthermore, an in vivo nude mouse colon cancer model was established to investigate the inhibitory effect of Gypenoside LI LI on colon cancer growth. Results In vitro experiments demonstrated that Gypenoside LI LI effectively inhibited the proliferation and migration of RKO and SW620 cells in a concentration? and time?dependent manner. Additionally, multiple fluorescence immunohistochemistry analyses revealed that the expression level of CPT1B in colon cancer tissues was significantly higher than that in adjacent non?tumor tissues. Gypenoside LI LI promoted ROS accumulation by inhibiting CPT1B expression. In vivo experiments further confirmed that Gypenoside LI LI could inhibit tumor formation in nude mice and reduce CPT1B expression. Conclusions This study elucidates the mechanism by which Gypenoside LI inhibits the growth of colon cancer cells. Specifically, it downregulates CPT1B, leading to increased accumulation of reactive oxygen species (ROS), disruption of fatty acid oxidation metabolism, and ultimately inducing apoptosis in colon cancer cells. These findings offer valuable insights into colon cancer treatment, suggesting new therapeutic strategies and potential drug targets.

Effect of Neuritin on angiogenesis of chicken embryo alantoic membrane and humar umbilical vein endothelial cells
Fuhua LIANG,Yunhua ZHANG,Xuan YANG,Yanmeng HOU,Guizhen LYU,Wenjie TANG,Li. YANG
2025, 41(2):  170-177.  doi:10.3969/j.issn.1006-5725.2025.02.003
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Objective To investigate the effects of neurotrophic factor Neuritin overexpression on the angiogenic effects of chicken embryonic allantoic membrane (CAM) and human umbilical vein endothelial cells (HUVECs), and to provide a new direction for the treatment of angiogenic diseases. Methods Thirty fresh yellow-skinned breeding eggs were selected to establish a CAM model, which were divided into three groups by randomized numerical table method: positive control group (bFGF), negative control group (NS) and experimental group (Neuritin), with 10 eggs in each group. The positive control group was loaded with 2 500 U/mL of bFGF, the experimental group was loaded with 10 μg/mL of Neuritin protein, and the negative control group was loaded with NS. 10 μL loading volume was loaded into each group, and all CAMs were incubated at the same temperature, relative humidity, and time, and the vascular branching, number, and size of the CAMs in each group were recorded after 72 h of incubation. Fresh umbilical cords from healthy pregnant women were selected to produce primary HUVECs, which were divided into three groups: transfected with recombinant plasmid (HUVEC-neu group), transfected with empty vector (HUVEC-3.1 group), and untransfected (HUVEC group). Primary HUVECs in the HUVEC-neu group were transfected with the recombinant plasmid Neuritin, and those in the HUVEC-3.1 group were transfected with the empty vector. HUVEC-3.1 group was transfected with the empty vector plasmid, and HUVEC group was not given any special treatment, and all three groups received the same culture regimen. Western blot was used to detect the protein expression level of Neuritin in HUVEC-3.1 and HUVEC-neu groups. CCK-8 assay, cell scratch assay, Transwell assay, and tube formation assay were used to detect protein expression level of Neuritin in HUVEC-3.1 group and HUVEC-neu group, and HUVEC-neu groups for cell proliferation, migration and tube formation. Results (1) The number of CAM vessel branch points and microvessels in the experimental group was significantly increased compared with that in the negative control group (P < 0.01), but there was no statistically significant difference in the number of large and medium-sized vessels between the two groups (P > 0.05); (2) Neuritin was successfully overexpressed in HUVECs in the HUVEC-neu group. (3) Compared with the HUVEC-3.1 group, the proliferation vigor of cells in the HUVEC-neu group was decreased (P < 0.05), but their migration and tube formation abilities were significantly enhanced (P < 0.01). Conclusion Neuritin overexpression promotes angiogenesis and participates in the regulation of neovascularization by affecting cell proliferation, migration, and tube formation ability.

Study on the mechanism of tetramethylpyrazine pretreatment umbilical cord mesenchymal stem cell transplantation in the treatment of ischemic stroke
Huiling CAO,Jie ZHANG,Xiaofei ZHU,Shining QIAN,Yunfeng. CHEN
2025, 41(2):  178-185.  doi:10.3969/j.issn.1006-5725.2025.02.004
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Objective To investigate the therapeutic effect, underlying mechanism, and key genes involved in tetramethylpyrazine-pretreated umbilical cord mesenchymal stem cell (ucMSC) transplantation in a rat model of ischemic stroke. Methods The rat MCAO model was established, and umbilical cord-derived mesenchymal stem cells (ucMSCs) pretreated with or without tetramethylpyrazine were transplanted via the tail vein. Neurological function scores, TTC staining, and infarct rates were assessed. Localization of ucMSCs in brain tissue was observed. Experimental groups were analyzed using chip technology, and sample data were standardized. Bioinformatics analysis was employed to identify differential genes, which were subsequently validated by PCR. Results The treatment effect in ucMSCs pretreated with tetramethylpyrazine group was significantly superior to that of the untreated group, as evidenced by a significant reduction in neurological function score, infarct rate, and infarct area observed through TTC staining. Moreover, the treated group exhibited a significantly higher number of ucMSCs located within brain injury tissues compared to the untreated group. Subsequently, 2905 differential mRNA were screened based on predetermined criteria, including 1 754 up-regulated and 1 151 down-regulated genes. Among these differentially expressed genes related to the chemokine signaling pathway (identified using a multiple change value ≥ 2.0 and P value ≤ 0.05), we identified 27 genes of interest. Notably, our analysis revealed activation of four genes closely associated with cell migration: Ccr6Ccr3Cxcr1 and Ccl6 respectively. Random verification experiments further confirmed a significant increase in gene expression for both Ccr3 and Cxcr1. Conclusions Pretreatment of umbilical cord-derived mesenchymal stem cells (ucMSCs) with tetramethylpyrazine significantly augmented the therapeutic efficacy in a rat model of ischemic stroke. Following pretreatment, there was a substantial increase in the migration of ucMSCs towards the site of brain injury. Our analysis suggests that this effect may be attributed to the activation of multiple chemokines, including Ccr6, Ccr3, Cxcr1, and Ccl6, by tetramethylpyrazine.

Effect of miR⁃378⁃5p on angiogenesis of glioma
Jiayi CAI,Siyu CHEN,Nyulue CAI,Wende. LI
2025, 41(2):  186-194.  doi:10.3969/j.issn.1006-5725.2025.02.005
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Objective To investigate the effect of miR-378-5p on glioma angiogenesis and its molecular mechanism. Methods The expression of miR-378-5p were detected by qRT-PCR in four glioma cells. The levels of VEGF were analyzed by ELISA. HUVECs were treated conditioned medium which collected by glioma cells supernatant. The effects of miR-378-5p on the proliferation, migration, invasion, and angiogenesis of HUVECs were detected by CCK-8, Transwell assay, and tubular formation assay. Results U251 was the highest expression of miR-378-5p, while U87 MG was the lowest expression. Glioma-conditioned media increased miR-378-5p levels significantly promoted the proliferation, migration, invasion, and angiogenesis of HUVECs. The results were contrary with glioma-conditioned media decreased miR-378-5p levels. miR-378-5p promoted the release of VEGF-A from glioma cells. The proliferation, migration, invasion, and angiogenesis of HUVECs treated-VEGF neutralizing antibody were significantly downregulated. Conclusion miR-378-5p promoted HUVECs proliferation, migration, invasion, and angiogenesis by increasing the release of VEGF from glioma cells.

Clinical Research
The association between early peripheral perfusion and acute kidney injury in patients admitted to the intensive care unit following major noncardiac surgery
Yujian CUI,Yuke LI,Sainan ZHU,Shuangling LI,Nan. LI
2025, 41(2):  195-201.  doi:10.3969/j.issn.1006-5725.2025.02.006
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Objective To investigate the association between early peripheral perfusion index (PPI) and acute kidney injury (AKI) in patients admitted to the intensive care unit (ICU) following major noncardiac surgery. Methods This retrospective cohort study was conducted at a single center. Adult patients consecutively enrolled were those admitted to the ICU after major noncardiac surgery. PPI measurements were collected within the first 6 hours post-surgery. The primary outcome assessed was the occurrence of AKI within 7 days after surgery. Multivariate logistic regression analysis was employed to adjust for confounding factors, while receiver operating characteristic (ROC) curve analysis determined the most predictive cutoff PPI. Results The study included a total of 444 patients who underwent noncardiac surgery. The incidences of postoperative AKI and severe AKI were 9.23% and 1.13%, respectively. Early postoperative PPI levels exhibited a skewed distribution, with a median value of 3.02 (2.02, 4.24). After adjusting for various perioperative variables, PPI was found to be independently correlated with the occurrence of postoperative AKI (OR = 0.734, 95% CI: 0.580~0.930, P = 0.010), as indicated by an area under the ROC curve of 0.680 2 (95% CI: 0.602 2 ~ 0.758 2, P < 0.001). Using a cutoff value of ≤ 2 .04 for PPI, the sensitivity and specificity for predicting postoperative AKI were determined to be approximately at 53.7 % and 77.2 % respectively. Further analysis revealed that patients with PPI ≤ 2.04 had a higher incidence of severe postoperative complications as well as prolonged mechanical ventilation duration and hospital stay. Conclusions A prompt reduction in postoperative PPI usage was found to be linked with the incidence of AKI occurring within 7 days following major noncardiac surgery.

Effects of short⁃term insemination and early rescue ICSI on pregnancy and neonatal outcomes
Hui WANG,Zhiheng CHEN,Li YANG,Yunhao LIANG,Huijiao WU,Yu JIANG,Shuai. LIU
2025, 41(2):  202-207.  doi:10.3969/j.issn.1006-5725.2025.02.007
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Objective This study aims to explore the impacts of short-term insemination and early rescue intracytoplasmic sperm injection (E-RICSI) on clinical and neonatal outcomes for IVF patients. Methods A retrospective analysis was conducted on the clinical data from the patients who underwent fresh embryo transfer at the Reproductive Center from January 2019 to December 2023. Patients were divided into four groups based on fertilization method: short-term IVF group (n = 204), conventional IVF group (n = 208), E-RICSI group (n = 13) and conventional ICSI group (n = 92). The fertilization rates, embryo development, pregnancy outcomes, and neonatal outcomes were compared between the short-term IVF and conventional IVF groups, and between the E-RICSI and conventional ICSI groups. Results There were no statistically significant differences in embryo development, clinical pregnancy, miscarriage, ectopic pregnancy, live birth rates, neonatal sex, and birth weight between the short-term IVF group and conventional IVF group. Similarly, no significant differences were observed in the E-RICSI group compared to the conventional ICSI group (P > 0.05). However, the fertilization rate (79.11% vs. 84.39%, P < 0.001) and the rate of 2PN zygotes (63.98% vs. 70.83%, P < 0.001) were significantly lower in the short-term IVF group compared to the conventional IVF group; The fertilization rate (65.49% vs. 91.68%, P < 0.001) and the rate of 2PN zygotes (57.75% vs. 88.35%, P < 0.001) were significantly lower in the E-RICSI group compared to the conventional ICSI group. Conclusions Although the fertilization rate of short-term insemination and E-RICSI is lower than that of conventional IVF and ICSI, it has no effect on embryonic development, pregnancy outcome and neonatal outcome. Short-term insemination combined with early rescue ICSI is an effective and safe technology to prevent complete fertilization failure.

Efficacy of ultrasound therapy combined with muscle imbalance adjustment training in patients with adhesive capsulitis oftheshoulder
Runhong CUI,Yan CHI,Di ZHANG,Hexiao GAO,Xue. JIANG
2025, 41(2):  208-214.  doi:10.3969/j.issn.1006-5725.2025.02.008
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Objective To explore the short and long term efficacy of ultrasound therapy combined with muscle imbalance adjustment training in patients with adhesive capsulitis(AC) ofthe shoulder. Methods A total of 60 AC patients were divided into an observation group and a control group, both each consisting of 30 cases. The observation group underwentultrasound therapy along with muscle imbalance adjustment training, while the control group received acupuncture treatment, both for a duration of 20 days. The Visual Analogue Scale(VAS), goniometer for ROM, Manual Muscle Testing(MMT),Constant-Murley Shoulder Score, and modified Barthel index were used to access shoulder jointpain level, range of motion (ROM), peripheral muscle strength, shoulder joint function, and daily living abilities, respectively. The Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD) were utilized to evaluate the levels of anxiety and depression.All the assessments were conducted and compared between the two groups before treatment, at the end of treatment, and at 6 and 12 months after treatment. Results Both groups showed varying degrees of improvement in ROM, MMT, VAS, Constant-Murley score, modified Barthel index, and emotional status compared to pre-treatment. The observation group demonstrated superior outcomes in posterior shoulder extension strength, VAS, Constant-Murley score, modified Barthel index, HAMA, and HAMD scores at the end of treatment (P < 0.05). At 6 months post-treatment, the observation group showed better shoulder joint flexion, extension, abduction, and adduction ROM, as well as muscle strength in flexion, external rotation, and internal rotation, VAS, Constant-Murley score, modified Barthel index, HAMA, and HAMD scores. At 12 months after treatment, the observation group continued to show superior outcomes in all the aforementioned indexes (P < 0.05). Conclusion The combination of ultrasound therapy and muscle imbalance adjustment training can effectively reduce shoulder joint pain, improve ROM, enhance muscle strength around the shoulder joint, improve shoulder joint function, alleviate anxiety and depression, and ultimately enhance the quality of life for patients with AC.

Changes in the ocular surface of patients with trigeminal neuralgia treated with percutaneous balloon compression of the trigeminal ganglion
Rui LIU,Shijuan WANG,Tieniu ZHENG,Wensheng. CHEN
2025, 41(2):  215-219.  doi:10.3969/j.issn.1006-5725.2025.02.009
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Objective To investigate the effect of percutaneous balloon compression on the ocular surface in the treatment of trigeminal neuralgia (TN). Methods A total of 30 patients (60 eyes) diagnosed with TN who underwent parallel balloon compression surgery from May 2023 to June 2024 were included in the study. Corneal sensation, Schirmer I test results, tear film break-up time (TBUT), and corneal fluorescein staining scores were evaluated in both eyes one day before and one day after the surgery. Results The tear secretion values and TBUT in both eyes of TN patients were lower than normal. Preoperatively, there were no statistically significant differences in various ocular examinations between the two eyes (P = 0.144, P = 0.072, P = 0.069, P = 1.000). One day postoperatively, the corneal sensitivity, tear secretion value, and TBUT of the affected eye were significantly lower compared to the contralateral eye (P < 0.01, P < 0.01, P < 0.01), while the fluorescein staining score showed a slight increase but was not statistically significant (P = 0.157). Compared to preoperative levels, the postoperative corneal sensitivity, tear secretion value, and TBUT of the affected side were significantly reduced (P < 0.01, P < 0.01, P < 0.01), while the fluorescein staining score showed a slight increase but remained non?significant (P = 0.157). Conclusions TN patients patients exhibit reduced bilateral tear secretion and compromised tear film stability. Following balloon compression surgery, the corneal sensitivity of the affected eye diminishes, leading to a further decline in tear secretion and tear film stability. Consequently, it is imperative that TN patients receive ophthalmic intervention, treatment, and regular follow?up, irrespective of whether they undergo surgery.

Clinical efficacy of testicular fascial compartment decompression in the treatment of testicular torsion in children
Peng XU,Yun ZHOU,Rong JIA,Can QI,Linmeng SHI,Jingda GAO,Dengwei CHU,Xu. GAO
2025, 41(2):  220-224.  doi:10.3969/j.issn.1006-5725.2025.02.010
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Objective To compare the efficacy of testicular repositioning and fixation combined with decompression of the testicular fascial compartment (testicular leucotomy + sheath flap repair) versus conventional testicular repositioning and fixation in surgery for testicular torsion in children. Methods Fifty-six patients with testicular torsion admitted to Hebei Provincial Children's Hospital from January 2019 to October 2023 were selected and divided into the observation group (26 cases) and the control group (30 cases), and the observation group was treated with testicular reorientation and fixation + testicular fascial compartment decompression, while the control group was treated with conventional testicular reorientation and fixation. There was no statistically significant difference in the age and left and right sides of the patients in the two groups (P > 0.05). The intraoperative bleeding, postoperative testicular atrophy, the presence of postoperative scrotal infection and postoperative hospitalization time of the two groups were compared. Results All patients successfully completed the operation without intraoperative complications. There was no statistically significant difference between the observation group and the control group in terms of intraoperative bleeding, postoperative scrotal infection rate and postoperative hospitalization time (P > 0.05); the postoperative testicular atrophy rate of the observation group was significantly lower than that of the control group (P < 0.05). Conclusions Testicular restoration and fixation + testicular fascial compartment decompression can effectively reduce the pressure of testicular fascial compartment, reduce the ischemia-reperfusion injury of testis, and reduce the occurrence of testicular atrophy, which is safe and effective in the treatment of testicular torsion in children.

Therapeutic effects of robot⁃assisted training combined with neural mobilization on upper limb functions in stroke patients
Yonglin HU,Yongping HUA,Ying MA,Anmin LU,Yuhua XIAO,Xinjian SONG,Su. LIU
2025, 41(2):  225-231.  doi:10.3969/j.issn.1006-5725.2025.02.011
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Objective To explore the effects of robot assisted training (RAT) combined with neural mobilization (NM) training on the recovery of upper limb functions in stroke patients. Methods A total of 110 stroke patients who met the inclusion criteria were selected as the subjects and randomly divided into a control group (n = 28), RAT group (n = 27), NM group (n = 28), and combination group (n = 27). All patients underwent routine upper limb occupational therapy. Additionally, the patients in the RAT group were treated with upper limb rehabilitation robots, those in the NM group underwent neural mobilization for treatment, those in the combination group were managed with robot-assisted training for upper limb rehabilitation and neural mobilization. Before treatment and 4 weeks after treatment, the modified Ashworth scale (MAS), Fugl-Meyer assessment upper extremity (FMA-UE), functional test for the hemiplegic upper extremity Hong Kong version (FTHUE-HK), and modified Barthel index (MBI) were used to assess the effects. The surface electromyographic signals of the biceps and triceps at the maximum isometric voluntary contraction (MIVC) position during elbow flexion and extension were measured, the integrated electromyographic values (iEMG) were recorded and the synergistic contraction rate (CR) was calculated. Results There was no statistically significant difference (P > 0.05) between the four groups in the general information and pre-treatment assessments of MAS, FMA-UE, FTHUE-HK, MBI, iEMG, and CR.After 4 weeks, significant improvements were observed in all indicators compared to the pre-treatment assessments (P < 0.05), with the exception of the triceps brachii CR, biceps brachii CR, and elbow extension MIVC biceps brachii iEMG in the control group.Among the group comparisons, all indicators showed statistically significant differences in mean or distribution (P < 0.05), except for MAS and triceps brachii CR. The RAT group, NM group, and combination group all demonstrated significant improvements compared to the control group (P < 0.05). Notably, the combination group exhibited a greater degree of improvement than the RAT and NM groups. Conclusion RATcombined with NM can reduce upper limb muscle tone in stroke patients. This approacheffectively promotes the establishment of normal movement patterns, improve upper limb motor function, and enhance activities of daily living. This combination is effective and worthy of further clinical promotion and application.

Expression of ACTN1 in cutaneous squamous cell carcinoma and its correlation with clinicopathological features and prognosis
Jinlan GUO,Xiaoning ZHANG,Jiahui JIANG,Tao. YUAN
2025, 41(2):  232-237.  doi:10.3969/j.issn.1006-5725.2025.02.012
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Objective To investigate the expression of ACTN1 in cutaneous squamous cell carcinoma (CSCC) and its association with clinicopathological features and prognosis. Methods A total of 150 patients with cutaneous squamous cell carcinoma (CSCC) and 100 healthy controls were enrolled in this study. The serum expression levels of ACTN1 were measured using ELISA. All CSCC patients underwent post?surgical follow?up and were categorized into a poor prognosis group (n = 69) and a good prognosis group (n = 81). Additionally, the 69 patients in the poor prognosis group were further classified into an ACTN1 lower expression subgroup (n = 35) and an ACTN1 higher expression subgroup (n = 34) based on the median expression level of ACTN1. Logistic regression analysis was employed to identify risk factors associated with poor prognosis in CSCC patients. ROC curve analysis was conducted to evaluate the clinical utility of serum ACTN1 expression levels in predicting poor prognosis in CSCC patients. Kaplan?Meier (K?M) survival analysis was utilized to assess the relationship between serum ACTN1 expression levels and the median time to poor prognosis in the 69 patients with poor prognosis. Furthermore, 40 additional CSCC patients were recruited to compare the expression levels of ACTN1 in CSCC tissues and adjacent tissues using immunohistochemistry. Results The serum expression levels of ACTN1 in the Control group and the CSCC group were (12.12 ± 2.26) ng/mL and (4.56 ± 1.02) ng/mL, respectively. Compared to the Control group, the serum expression level of ACTN1 in the CSCC group was significantly decreased, and the difference was statistically significant (t = 31.37, P < 0.001)。 In the poor prognosis group, the proportion of tumors with a diameter ≥ 5 cm, low degree of tumor cell differentiation, subadipocyte invasion depth, lymph node metastasis incidence, and serum ACTN1 expression levels were all significantly higher compared to the good prognosis group, with statistical significance (P < 0.05). Logistic regression analysis revealed that lymph node metastasis (OR = 3.253) and elevated ACTN1 expression (OR = 2.894) were independent risk factors for poor prognosis following CSCC surgery. The area under the curve (AUC) for serum ACTN1 expression in predicting poor prognosis post?surgery in CSCC patients was 0.911. At a cut?off value of 13.19 ng/mL for ACTN1, the diagnostic sensitivity and specificity were 89.78% and 92.12%, respectively. The median time to poor prognosis was 25 months in the ACTN1 low?expression group and 18.5 months in the ACTN1 high?expression group, respectively. The median time to poor prognosis was significantly shorter in the ACTN1 high?expression group compared to the low?expression group (HR = 6.627, P < 0.001). Among 40 CSCC tissue samples, 32 cases exhibited higher ACTN1 expression, while 8 cases showed lower expression. In contrast, among 40 paracancerous tissue samples, 11 cases had higher ACTN1 expression and 29 cases had lower expression. The higher expression rate of ACTN1 in CSCC tissues was significantly elevated compared to paracancerous tissues (χ2 = 22.175, P < 0.001). Conclusion The serum expression level of ACTN1 in CSCC patients was significantly elevated, suggesting its potential as a biomarker for assessing post?surgical prognosis in CSCC patients.

Correlation between plasma ADAMTS13 level, disease severity and prognosis in patients with endometriosis
Ke XU,Mingzhe ZHANG,Mingyang WANG,Song. LIU
2025, 41(2):  238-243.  doi:10.3969/j.issn.1006-5725.2025.02.013
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Objective To investigate the relationship between plasma von willebrand factory-lytic protease (ADAMTS13) level and the severity of the disease and its prognostic value in patients with endometriosis (EMS). Methods 130 patients with EMS treated in the hospital from January 2019 to December 2022 were retrospectively selected. Plasma ADAMTS13 level was detected by enzyme-linked immunosorbent assay (ELISA), and its correlation with American Fertility Society (r-AFS) stage and endometriosis Health Status Scale (EHP-30) score was analyzed. The 1-year prognosis was recorded, and the risk factors of poor prognosis were analyzed by logistic regression. Receiver operating characteristic curve (ROC) was plotted to evaluate the predictive value of plasma ADAMTS13 levels in patients with EMS. Results The plasma ADAMTS13 level of EMS patients decreased significantly with the increase of r-AFS stage, and was negatively correlated with the score of EHP-30 (P < 0.001). Multiple factors showed that low plasma ADAMTS13 level, bilateral location of pelvic lesions and high r-AFS stage were independent risk factors for poor prognosis (all P < 0.05). ROC analysis showed that the area under the curve (AUC) of plasma ADAMTS13 was 0.889 (cut-off point 13.315, sensitivity 0.931, specificity 0.690). Conclusion Plasma ADAMTS13 level is negatively correlated with the severity of EMS, and is an independent risk factor for poor prognosis of EMS patients, and has a certain predictive value for prognosis of EMS patients.

Elderly acute progressive cerebral infarction patients′ serum PLA2, called S100B levels and the relationship between carotid plaques
Yanyan JIA,Yijia SUN,Di ZHAO,Yan. SONG
2025, 41(2):  244-249.  doi:10.3969/j.issn.1006-5725.2025.02.014
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Objective To explore the relationship between serum phospholipase A2(PLA2), S100 calcium-binding protein B(S100B) and carotid plaque in elderly patients with acute progressive cerebral infarction. Methods From January 2021 to June 2022, 120 elderly patients with acute progressive cerebral infarction were enrolled in the study group, while 115 patients with non-progressive cerebral infarction were classified as non-progressive group and 100 healthy people as healthy group. The study group was divided into three groups: no plaque group (34 cases), stable plaque group (45 cases) and unstable plaque group (41 cases). To analyze the relationship between serum PLA2 and S100B levels and carotid plaque. ROC analysis of their predictive value for carotid plaque. Follow-up for 1 year, the survival rate was analyzed with recurrence and death as the end points. Results The levels of serum PLA2 and S100B in stable and unstable plaque groups were higher than those in non-plaque group, and the difference was statistically significant (P < 0.05). Serum PLA2 and S100B were positively correlated with carotid plaque. ROC showed that the value of joint prediction was higher (P<0.05). Conclusion The levels of serum PLA2 and S100B are increased in elderly patients with acute progressive cerebral infarction, which is closely related to carotid plaque.

Drugs and Clinic Practice
Changes in complex networks of brain functions associated with sodium channel blocker drug treatment in temporal lobe epilepsy
Cuimi LUO,Zirong CHEN,Dongying HUANG,Jin′ou. ZHENG
2025, 41(2):  250-257.  doi:10.3969/j.issn.1006-5725.2025.02.015
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Objective To investigate the changes in the complex network of brain functions associated with sodium channel blocker (SCB) treatment and the neural mechanisms underlying the effects on executive control functions. Methods Twenty-one patients with temporal lobe epilepsy taking SCB (TLE-SCB) and 12 patients with temporal lobe epilepsy not taking SCB (TLE-N) were enrolled in the study along with 18 healthy controls (HC). Resting-state functional magnetic resonance imaging (rsfMRI) and attentional network testing (ANT) were completed, and graph theoretic methods were applied to study the changes in the complex networks of brain function in the three groups of subjects, and to investigate the relationship between changes in brain networks and executive function. Results The TLE-SCB and TLE-N groups showed executive function impairment compared to the HC group. Analysis of brain network topological properties showed that multiple node median centrality was reduced in the TLE-SCB group compared to the TLE-N group (all Bonferroni corrected, P < 0.017); right amygdala node clustering coefficient, and local efficiency of the left suboccipital gyrus were reduced (t = -2.953, P = 0.006; t = -2.597, P = 0.0142). The TLE-SCB compared to the HC group had decreased multiple node median centrality (all Bonferroni corrected, P < 0.017); increased node clustering coefficients in the left orbital middle frontal gyrus (t = 2.861, P = 0.007); and decreased localized efficiency in the left inferotemporal gyrus (t = -2.870, P = 0.007). The TLE-N group compared to the HC group had decreased right paracentral lobule mediator centrality, local efficiency increased (t = 2.644, P = 0.013; t = 3.464, P = 0.002); right amygdala node clustering coefficient increased (t = 2.884, P = 0.007). Correlation analysis showed that decreased centrality of left suboccipital gyrus mediators was negatively correlated with executive efficiency in the TLE-SCB group (P = 0.045, r = -0.441). Conclusion Patients using SCB medication showed impairment of brain functional network topological properties, with the left suboccipital gyrus as an important node; altered brain functional network topological properties may underlie the network of cognitive impairment in SCB.

Medical Examination and Clinical Diagnosis
Evaluation of plasma PPARγ as a potential diagnostic marker for female interstitial cystitis/painful bladder syndrome and its predictive model
Zhao WANG,Jiepeng ZUO,Hang CHE,Lingyun REN,Zhe XU,Lei. WANG
2025, 41(2):  258-263.  doi:10.3969/j.issn.1006-5725.2025.02.016
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Objective To investigate the correlation between PPARγ and female interstitial cystitis/bladder pain syndrome (IC/BPS) and to establish a predictive model. Methods Clinical data were collected from 89 female IC/BPS patients (observational group) admitted to the hospital from June 2022 to December 2023, and 90 healthy female volunteers undergoing physical examinations during the same period (control group). Plasma levels of inflammatory factors, total antioxidant capacity (TAC), total glutathione (GSH), malondialdehyde (MDA), and PPARγ levels were measured. Significant clinical features were identified using LASSO regression and fitted into a multivariate logistic regression model. The diagnostic efficacy was assessed through receiver operating characteristic (ROC) curves. Results Compared to the control group, the observation group exhibited significantly elevated age, BMI, NLR, absolute neutrophil count, IFN-α, IL-1β, IL-6, IL-8, TNF-α and CD3+CD4+T expression levels, while absolute lymphocyte count, IL-10, TAC, GSH and plasma PPARγ expression levels were significantly decreased (all P < 0.05). LASSO regression identified 8 variables, including NLR, IFN-α, absolute neutrophil count, IL-1β, IL-6, TNF-α, CD3+CD4+T and PPARγ, which were incorporated into the predictive model. Multivariate binary logistic regression analysis revealed that elevated levels of IL-1β, TNF-α and CD3+CD4+T cells, along with reduced PPARγ levels, were independent risk factors for IC/BPS. ROC curve analysis indicated that the diagnostic efficacy of the combined PPARγ and clinical parameters (age, IL-1β, TNF-α and CD3+CD4+T) (AUC = 0.901) was superior to PPARγ alone (AUC = 0.839). Conclusion Plasma PPARγ levels are significantly reduced in female IC/BPS patients and serve as a potential diagnostic marker, with combined clinical parameters enhancing diagnostic accuracy.

Clinical significance of CT perfusion imaging combined with artificial intelligence in evaluating reperfusion injury after cerebral infarction
Wei LU,Pan ZHANG,Yushu. QIN
2025, 41(2):  264-270.  doi:10.3969/j.issn.1006-5725.2025.02.017
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Objective To analyze the significance of CT perfusion imaging combined with artificial intelligence (AI) in evaluating reperfusion injury after cerebral infarction. Methods 106 patients with cerebral infarction admitted to the hospital from January 2019 to October 2023 were prospectively selected as the study objects. Patients were divided into reperfusion injury group and no perfusion injury group according to whether reperfusion injury occurred after 14 days of thrombolytic therapy. CT perfusion imaging and AI parameters were compared between reperfusion injury group and non-perfusion injury group. The factors affecting reperfusion injury in cerebral infarction patients after thrombolytic therapy were analyzed. The value of CT perfusion imaging parameters combined with AI in predicting reperfusion injury after thrombolytic therapy in cerebral infarction patients was analyzed. Results 31 cases had reperfusion injury, and the other 75 cases had no perfusion injury. CBF, average CT value and entropy level in the reperfusion injury group were lower than those in the non-perfusion injury group (P < 0.05), CBV, MTT, TTP and kurtosis were higher than those in the non-perfusion injury group (P < 0.05). Logistic regression analysis showed that NIHSS (OR = 5.228, 95%CI: 2.151 ~ 12.705), CBF(OR = 3.777, 95%CI: 1.554 ~ 9.180), CBV(OR = 3.699, 95%CI: 1.522 ~ 9.989) and average CT value (OR = 4.125, 95%CI: 1.697 ~ 10.024) were the influencing factors of reperfusion injury in cerebral infarction patients after thrombolytic therapy (P < 0.05). ROC curve results showed that the sensitivity of CBF, CBV, average CT value and their combination in predicting reperfusion injury after thrombolytic therapy in cerebral infarction patients were 67.74%, 70.97%, 77.42%, 87.10%, and the specificity were 70.67%, 74.67%, 77.33%, 90.67%, AUC values were 0.665, 0.667, 0.744 and 0.908. Conclusion CT perfusion imaging combined with AI is effective in evaluating reperfusion injury after cerebral infarction.

Screening of anti⁃fetal hemoglobin monoclonal antibodies based on trailing count method and its application in preliminary diagnostic method for β⁃thalassemia
Moli YIN,Jingzhe XU,Yu YAN,Zhenxiao TONG,Lei LIU,Huiyan. WANG
2025, 41(2):  271-277.  doi:10.3969/j.issn.1006-5725.2025.02.018
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Objective To establish an initial diagnostic method for β-thalassemia (BT) using a double antibody sandwich ELISA approach. Methods The hybridoma producing monoclonal antibodies against anti-HbF were screened using a trailing count method. The mAbs were evaluated through ELISA, modified immunocytochemistry, and Western blot analysis. A double antibody-sandwich ELISA assay was established by labeling the pairs of mAbs with ALP using the glutaral method, and this detection system was used to analyze 40 serum samples. Results The results demonstrate the successful generation of nine hybridoma cell lines capable of secreting highly active anti-HbF monoclonal antibodies (mAbs). Specifically, four mAbs (3F7, 4G1, 6C1, and 9H7) exhibited exclusive reactivity towards HbF without any cross-reactivity with hemoglobin variants (HbA and HbA2). These four HbF-specific mAbs displayed exceptional specificity and sensitivity, with a maximum titer of 1∶256 000 and the highest affinity constant (Ka) recorded at 2.36×108 L/mol. Among these mAbs, optimal antibody pairing was achieved using capture antibody 3F7 in conjunction with ALP-4G1 for the development of a sandwich ELISA detection method. By employing this approach, fetal and healthy human blood samples were successfully quantified for HbF levels with an impressive detection sensitivity reaching up to 80%. Conclusion This sandwich ELISA demonstrated precise quantification of HbF levels, making it suiTab.for both research and diagnostic purposes in the field of β-thalassemia.

Investigations
Study on the association between gaseous pollutants and cardiovascular disease hospitalization, hospitalization costs, and hospitalization days in seven cities of Guangdong province
Xingyu CHEN,Ying XIAO,Hualiang LIN,Lawrence Lam.
2025, 41(2):  278-287.  doi:10.3969/j.issn.1006-5725.2025.02.019
Abstract ( 127 )   HTML ( 5)   PDF (1115KB) ( 45 )  
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Objective To investigate the impact of gaseous pollutants (SO2, NO2, CO, O3) on hospital admissions, hospitalization costs, and length of stay for cardiovascular diseases in seven cities of Guangdong Province. Methods A total of 2,010,905 patients with cardiovascular diseases from seven cities in Guangdong Province between January 2017 and December 2019 were included. Demographic characteristics and hospitalization data for cardiovascular disease inpatients were obtained from the Guangdong Province Electronic Healthcare Information System. Daily exposure concentrations of SO2, NO2, CO and O3 were extracted from the China High?Air?Pollution Dataset. The impact of air pollutants on cardiovascular diseases in the seven cities of Guangdong Province was estimated using a multi?step time?series analysis. Results SO2, NO2, and CO concentrations on the day of admission (lag0) were positively associated with the risk of cardiovascular admissions, hospitalization costs, and length of stay, with NO2 exhibiting the strongest effect. Additionally, there was a lagged negative impact of NO2 and CO, while O3 concentrations were inversely correlated with the number of cardiovascular admissions, hospitalization costs, and length of stay over the lag0?7 period. Conclusions Short?term exposures to SO2, NO2, and CO are likely positively associated with the disease burden in CVD patients. Furthermore, given the more substantial adverse effects of NO2, enhanced monitoring of NO2 remains essential. However, as this study is retrospective, additional research is warranted.

Reviews
Research progress on the antitumor effects of immune checkpoint inhibitors
Qiang FU,Zhongqi LU,Ying CHANG,Tiefeng JIN,Meihua. ZHANG
2025, 41(2):  288-293.  doi:10.3969/j.issn.1006-5725.2025.02.020
Abstract ( 193 )   HTML ( 11)   PDF (470KB) ( 525 )  
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Tumor immunotherapy has emerged as a highly esteemed and rapidly evolving field in recent years, marked by the development of numerous significant therapeutic approaches. Among these, immune checkpoint inhibitors stand out as a pivotal strategy, attracting considerable attention due to their substantial research progress. This article provides a comprehensive review of the current research advancements in ten key immune checkpoints related to anti?tumor therapy, including PD?1/PD?L1, CTLA?4, LAG?3, TIM?3, TIGIT, and VISTA. By conducting an in?depth analysis of their mechanisms of action, clinical applications, and future research directions, this review aims to offer valuable insights and guidance for optimizing strategies in tumor immunotherapy.

Research advances of mesenchymal stem cells in the bone marrow microenvironment of acute myeloid leukemia
Xingyu WAN,Nan LI,Shuiqing LIU,Xi. ZHANG
2025, 41(2):  294-299.  doi:10.3969/j.issn.1006-5725.2025.02.021
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Acute myeloid leukemia (AML) is a highly heterogeneous hematological malignancy, driven by multiple gene mutations and characterized by high incidence and mortality rates. Mesenchymal stem cells (MSCs), which possess self?renewal and multidirectional differentiation potentials, play crucial roles within the bone marrow microenvironment. Emerging research has demonstrated that MSCs contribute to AML development through various mechanisms, including mitochondrial transfer, transmission of extracellular vesicles, adipogenic differentiation, and secretion of pro?cancer proteins. This review provides a comprehensive summary of the involvement of MSCs in the AML bone marrow microenvironment and offers insights for developing novel therapeutic strategies targeting MSCs in AML treatment.

Research progress on skin grafting for the treatment of stable vitiligo
Lu CAO,Yang. ZHAO
2025, 41(2):  300-304.  doi:10.3969/j.issn.1006-5725.2025.02.022
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Vitiligo is a common disfiguring skin disorder characterized by patches of depigmentation or hypopigmentation on the skin or mucosa. Clinically, vitiligo can be categorized into progressive and stable stages. For stable vitiligo, surgical skin grafting is an essential therapeutic approach. This article systematically reviews the current commonly used skin grafting techniques for vitiligo treatment, including the advancements in tissue grafting and cellular grafting technologies. Additionally, it discusses advancements in novel grafting adjunctive techniques and postoperative care improvements that contribute to increased graft success rates.