1.Distribution of Traditional Chinese Medicine Syndrome Elements in Different Risk Populations of Heart Failure Complicated with Type 2 Diabetes: A Retrospective Study Based on Nomogram Model and Factor Analysis
Tingting LI ; Zhipeng YAN ; Yajie FAN ; Wenxiu LI ; Wenyu SHANG ; Yongchun LIANG ; Yiming ZUO ; Yuxin KANG ; Boyu ZHU ; Junping ZHANG
Journal of Traditional Chinese Medicine 2025;66(11):1140-1146
ObjectiveTo analyze the distribution characteristics of traditional Chinese medicine (TCM) syndrome elements in different risk populations of heart failure complicated with type 2 diabetes. MethodsClinical data of 675 type 2 diabetes patients were retrospectively collected. Lasso-multivariate Logistic regression was used to construct a clinical prediction nomogram model. Based on this, 441 non-heart failure patients were divided into a low-risk group (325 cases) and a high-risk group (116 cases) according to the median risk score of heart failure complicated with type 2 diabetes. TCM diagnostic information (four diagnostic methods) was collected for both groups, and factor analysis was applied to summarize the distribution of TCM syndrome elements in different risk populations. ResultsLasso-multivariate Logistic regression analysis identified age, disease duration, coronary heart disease, old myocardial infarction, arrhythmia, absolute neutrophil count, activated partial thromboplastin time, and α-hydroxybutyrate dehydrogenase as independent risk factors for heart failure complicated with type 2 diabetes. These were used as final predictive factors to construct the nomogram model. Model validation results showed that the area under the curve (AUC) of the receiver operating characteristic (ROC) curve for the modeling group and validation group were 0.934 and 0.935, respectively. The Hosmer-Lemeshow test (modeling group P = 0.996, validation group P = 0.121) indicated good model discrimination. Decision curve analysis showed that the curves for All and None crossed in the upper right corner, indicating high clinical utility. The low-risk and high-risk groups each obtained 14 common factors. Preliminary analysis revealed that the main disease elements in the low-risk group were qi deficiency (175 cases, 53.85%), dampness (118 cases, 36.31%), and heat (118 cases, 36.31%), with the primary locations in the spleen (125 cases, 38.46%) and lungs (99 cases, 30.46%). In the high-risk group, the main disease elements were yang deficiency (73 cases, 62.93%), blood stasis (68 cases, 58.62%), and heat (49 cases, 42.24%), with the primary locations in the kidney (84 cases, 72.41%) and heart (70 cases, 60.34%). ConclusionThe overall disease characteristics in different risk populations of type 2 diabetes patients with heart failure are a combination of deficiency and excess, with deficiency being predominant. Deficiency and heat are present throughout. The low-risk population mainly shows qi deficiency with dampness and heat, related to the spleen and lungs. The high-risk population shows yang deficiency with blood stasis and heat, related to the kidneys and heart.
2.Huoxue Jiedu Formulas (活血解毒方药) as an Adjunctive Therapy for Patients with Binding of Stasis and Toxin Syndrome during the Vulnerable Period after Myocardial Infarction:A Prospective Real-World Study
Xiaofei GENG ; Yingxi YANG ; Zhipeng YAN ; Xinbiao FAN ; Xitong SUN ; Boyu ZHU ; Zheng ZHANG ; Yongchun LIANG ; Xiaoyu SHAN ; Junping ZHANG
Journal of Traditional Chinese Medicine 2025;66(23):2467-2474
ObjectiveTo observe the efficacy of Huoxue Jiedu Formulas (活血解毒方药, HJF) as an adjunctive treatement for patients with binding of stasis and toxin syndrome during the vulnerable period after acute myocardial infarction (AMI) percutaneous coronary intervention (PCI) surgery, and to explore its potential mechanism from the perspective of serum neutrophil extracellular traps (NETs). MethodsA total of 129 patients with binding of stasis and toxin syndrome within 6 months after PCI for AMI were enrolled and divided into a treatment group (65 cases) and a control group (64 cases) based on patients' willingness to take Chinese herbal medicine. The control group received standard western medical therapy alone, while the treatment group additionally received HJF, one dose daily. Both groups were treated for four weeks. Before and after treatment, TCM syndrome scores were assessed. Seattle angina questionnaire (SAQ) was used to record angina stability and frequency scores, while the short form-36 health survey (SF-36) was employed to assess quality of life across eight dimensions, including physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. The Pittsburgh sleep quality index (PSQI) was used to evaluate sleep quality, and the patient health questionnaire-15 (PHQ-15) was used to assess psychosomatic symptoms; Duke activity status index (DASI) was used to measure daily physical activity. Serum levels of neutrophil extracellular traps (NET) markers including myeloperoxidase-DNA (MPO-DNA), neutrophil elastase-DNA (NE-DNA), and citrullinated histone H3 (CitH3) were measured in 20 patients from the treatment group. ResultsAfter treatment, TCM syndrome score, PSQI score and PHQ-15 score in both groups significantly decreased, while DASI score, angina stability and frequency scores, and all eight dimensions of the SF-36 scale significantly increased (P<0.05). Compared to the control group, the treatment group had significantly lower TCM syndrome scores and significantly higher DASI, angina stability and frequency scores (P<0.05), as well as higher scores in the SF-36 dimensions of physical functioning, role-physical, social functioning, bodily pain, and vitality (P<0.05). After treatment, serum levels of MPO-DNA, CitH3, and NE-DNA in the treatment group were significantly reduced (P<0.05). ConclusionHJF combined with conventional therapy can significantly improve angina symptoms, TCM syndrome scores, and psychosomatic conditions in patients with binding of stasis and toxin syndrome during the vulnerable period after AMI. It also enhances quality of life, sleep quality, and daily physical activity. The underlying mechanism may be associated with the inhibition of serum NETs level.
3.Role and mechanisms of histone methylation in osteogenic/odontogenic differentiation of dental mesenchymal stem cells.
International Journal of Oral Science 2025;17(1):24-24
Dental mesenchymal stem cells (DMSCs) are pivotal for tooth development and periodontal tissue health and play an important role in tissue engineering and regenerative medicine because of their multidirectional differentiation potential and self-renewal ability. The cellular microenvironment regulates the fate of stem cells and can be modified using various optimization techniques. These methods can influence the cellular microenvironment, activate disparate signaling pathways, and induce different biological effects. "Epigenetic regulation" refers to the process of influencing gene expression and regulating cell fate without altering DNA sequences, such as histone methylation. Histone methylation modifications regulate pivotal transcription factors governing DMSCs differentiation into osteo-/odontogenic lineages. The most important sites of histone methylation in tooth organization were found to be H3K4, H3K9, and H3K27. Histone methylation affects gene expression and regulates stem cell differentiation by maintaining a delicate balance between major trimethylation sites, generating distinct chromatin structures associated with specific downstream transcriptional states. Several crucial signaling pathways associated with osteogenic differentiation are susceptible to modulation via histone methylation modifications. A deeper understanding of the regulatory mechanisms governing histone methylation modifications in osteo-/odontogenic differentiation and immune-inflammatory responses of DMSCs will facilitate further investigation of the epigenetic regulation of histone methylation in DMSC-mediated tissue regeneration and inflammation. Here is a concise overview of the pivotal functions of epigenetic histone methylation at H3K4, H3K9, and H3K27 in the regulation of osteo-/odontogenic differentiation and renewal of DMSCs in both non-inflammatory and inflammatory microenvironments. This review summarizes the current research on these processes in the context of tissue regeneration and therapeutic interventions.
Mesenchymal Stem Cells/physiology*
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Humans
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Osteogenesis/genetics*
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Histones/metabolism*
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Cell Differentiation/physiology*
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Methylation
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Odontogenesis/genetics*
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Epigenesis, Genetic
4.Comparative observation of subretinal and intravitreal injection of Conbercept after pars plana vitrectomy in the treatment of refractory diabetic macular edema
Wanxuan CHAI ; Wei WU ; Kangcheng LIU ; Hanying HU ; Huimin FAN ; Xiaohan SU ; Zhipeng YOU
Chinese Journal of Ocular Fundus Diseases 2025;41(1):25-31
Objective:To compare the efficacy of pars plana vitrectomy (PPV) combined with subretinal or intravitreal injection of Conbercept for the treatment of refractory diabetic macular edema (DME).Methods:A retrospective case control study. From June 2022 to March 2024, 32 eyes of 32 patients with refractory DME diagnosed at The Affiliated Eye Hospital of Nanchang University were included in the study. There were 17 male cases with 17 eyes and 15 female cases with 15 eyes. Age was (57.44±8.99) years old; The duration of diabetes was (12.72±6.11) years. All patients had received regular treatment with anti-vascular endothelial growth factor (VEGF) drugs or corticosteroid drugs for at least 5 times, and had undergone focal retinal laser photocoagulation or panretinal laser photocoagulation, the central macular thickness (CMT) persisted or decreased by less than 50 μm. All affected eyes underwent best-corrected visual acuity (BCVA), intraocular pressure, optical coherence tomography (OCT), microperimetry, and laboratory glycated hemoglobin (HbA1c) testing. BCVA was measured using a standard logarithmic visual acuity chart, and converted to the logarithm of the minimum angle of resolution (logMAR) for statistical analysis. CMT was measured using an OCT device. Microperimetry was performed using an MP-3 microperimeter, recording the mean sensitivity (MS) of the retina within a 12° range of the fovea. The affected eyes were treated with 23G PPV combined with internal limiting membrane peeling and either macular subretinal or intravitreal injection of Conbercept, and were divided into subretinal injection group and the intravitreal injection group, each consisting of 16 cases and 16 eyes. The same equipment and methods as before surgery were used for related examinations at 1, 3, and 6 months post-surgery. Changes in BCVA, CMT, and MS were observed and compared, as well as the number of additional anti-VEGF treatments required within 6 months after surgery. Intergroup comparisons were made using independent samples t tests, and repeated measures data were analyzed using repeated measures analysis of variance. Results:The age ( t=-0.271), gender composition ( χ2=0.001), duration of diabetes ( Z=-0.868), HbA1c ( t=-0.789), intraocular pressure ( t=1.689), logMAR BCVA ( t=1.393), CMT ( t=-0.613), MS ( Z=-0.132), and the number of anti-VEGF injections ( t=-0.752) between the subretinal injection group and the intravitreal injection group showed no statistically significant differences ( P>0.05). The within-subject effects comparison of BCVA, CMT, and MS at 1, 3, and 6 months post-surgery compared to pre-surgery for all affected eyes showed statistically significant differences ( F=8.060, 125.722, 39.054; P<0.05). The overall comparison of logMAR BCVA between the subretinal and intravitreal injection groups post-surgery showed no statistically significant difference ( F=0.662, P=0.422), however, comparisons of CMT ( F=4.540) and MS ( F=6.066) showed statistically significant differences ( P<0.05). At 1, 3, and 6 months post-surgery, comparisons of logMAR BCVA between the two groups showed no statistically significant differences ( t=-0.123, 0.239, 1.087; P>0.05), comparisons of CMT showed statistically significant differences ( t=-3.474, -4.832, -2.482; P<0.05), comparisons of MS showed statistically significant differences at 1 and 3 months ( t=-2.940, -2.545; P<0.05), but not at 6 months ( t=-1.527, P>0.05). At 6 months post-surgery, the number of additional intravitreal anti-VEGF injections required in the subretinal and intravitreal injection groups showed a statistically significant difference ( Z=-2.033, P=0.042). During the follow-up period and at the final follow-up, no complications such as injection site bleeding, retinal detachment, vitreous hemorrhage, macular hole, or retinal pigment epithelial tear or atrophy occurred in all affected eyes. Conclusion:Compared with intravitreal injection, subretinal injection of Conbercept for the treatment of refractory DME has more advantages in reducing macular edema and improving visual function in the macular area, and also reduces the number of postoperative anti-VEGF drug treatments.
5.Comparative observation of subretinal and intravitreal injection of Conbercept after pars plana vitrectomy in the treatment of refractory diabetic macular edema
Wanxuan CHAI ; Wei WU ; Kangcheng LIU ; Hanying HU ; Huimin FAN ; Xiaohan SU ; Zhipeng YOU
Chinese Journal of Ocular Fundus Diseases 2025;41(1):25-31
Objective:To compare the efficacy of pars plana vitrectomy (PPV) combined with subretinal or intravitreal injection of Conbercept for the treatment of refractory diabetic macular edema (DME).Methods:A retrospective case control study. From June 2022 to March 2024, 32 eyes of 32 patients with refractory DME diagnosed at The Affiliated Eye Hospital of Nanchang University were included in the study. There were 17 male cases with 17 eyes and 15 female cases with 15 eyes. Age was (57.44±8.99) years old; The duration of diabetes was (12.72±6.11) years. All patients had received regular treatment with anti-vascular endothelial growth factor (VEGF) drugs or corticosteroid drugs for at least 5 times, and had undergone focal retinal laser photocoagulation or panretinal laser photocoagulation, the central macular thickness (CMT) persisted or decreased by less than 50 μm. All affected eyes underwent best-corrected visual acuity (BCVA), intraocular pressure, optical coherence tomography (OCT), microperimetry, and laboratory glycated hemoglobin (HbA1c) testing. BCVA was measured using a standard logarithmic visual acuity chart, and converted to the logarithm of the minimum angle of resolution (logMAR) for statistical analysis. CMT was measured using an OCT device. Microperimetry was performed using an MP-3 microperimeter, recording the mean sensitivity (MS) of the retina within a 12° range of the fovea. The affected eyes were treated with 23G PPV combined with internal limiting membrane peeling and either macular subretinal or intravitreal injection of Conbercept, and were divided into subretinal injection group and the intravitreal injection group, each consisting of 16 cases and 16 eyes. The same equipment and methods as before surgery were used for related examinations at 1, 3, and 6 months post-surgery. Changes in BCVA, CMT, and MS were observed and compared, as well as the number of additional anti-VEGF treatments required within 6 months after surgery. Intergroup comparisons were made using independent samples t tests, and repeated measures data were analyzed using repeated measures analysis of variance. Results:The age ( t=-0.271), gender composition ( χ2=0.001), duration of diabetes ( Z=-0.868), HbA1c ( t=-0.789), intraocular pressure ( t=1.689), logMAR BCVA ( t=1.393), CMT ( t=-0.613), MS ( Z=-0.132), and the number of anti-VEGF injections ( t=-0.752) between the subretinal injection group and the intravitreal injection group showed no statistically significant differences ( P>0.05). The within-subject effects comparison of BCVA, CMT, and MS at 1, 3, and 6 months post-surgery compared to pre-surgery for all affected eyes showed statistically significant differences ( F=8.060, 125.722, 39.054; P<0.05). The overall comparison of logMAR BCVA between the subretinal and intravitreal injection groups post-surgery showed no statistically significant difference ( F=0.662, P=0.422), however, comparisons of CMT ( F=4.540) and MS ( F=6.066) showed statistically significant differences ( P<0.05). At 1, 3, and 6 months post-surgery, comparisons of logMAR BCVA between the two groups showed no statistically significant differences ( t=-0.123, 0.239, 1.087; P>0.05), comparisons of CMT showed statistically significant differences ( t=-3.474, -4.832, -2.482; P<0.05), comparisons of MS showed statistically significant differences at 1 and 3 months ( t=-2.940, -2.545; P<0.05), but not at 6 months ( t=-1.527, P>0.05). At 6 months post-surgery, the number of additional intravitreal anti-VEGF injections required in the subretinal and intravitreal injection groups showed a statistically significant difference ( Z=-2.033, P=0.042). During the follow-up period and at the final follow-up, no complications such as injection site bleeding, retinal detachment, vitreous hemorrhage, macular hole, or retinal pigment epithelial tear or atrophy occurred in all affected eyes. Conclusion:Compared with intravitreal injection, subretinal injection of Conbercept for the treatment of refractory DME has more advantages in reducing macular edema and improving visual function in the macular area, and also reduces the number of postoperative anti-VEGF drug treatments.
6.Efficient AAV8 delivery to the liver via isolated hepatic perfusion and analysis of hepatic lobule transduction patterns
Chao Wang ; Mingming Fan ; Jianrong Liu ; Xiaolu Guo ; Zhipeng Tan ; Xueying Huang ; Zhuoran Li ; Xiaomei Liu ; Ye Zhang ; Jianqi Feng ; Rui Fang ; Li Wang ; Qiong Ke
Liver Research 2025;9(4):313-323
Background and aims
Adeno-associated virus (AAV) is becoming an attractive vector due to its low toxicity and minimal immunogenicity. However, liver-targeted AAV gene therapy still faces challenges, such as low delivery efficiency and safety risks associated with high vector doses. Isolated hepatic perfusion (IHP) has been explored as a localized drug delivery method, yet its full potential in gene therapy remains under investigation. Here, we investigated the efficiency of AAV8 delivery via the IHP route and its preference for hepatic transduction.
Methods
The IHP route was established through surgery in rats and cynomolgus monkey, and the AAV8-dTomato solution was injected into the entire liver through the inflow tract and maintained for 10 min. One week later, liver tissues were obtained, and the dTomato fluorescence expression area fraction and intensity were analyzed.
Results
AAV8-dTomato delivery via the IHP resulted in over 60% dTomato-positive areas in rat liver and showed higher efficiency than the portal vein (PV) and inferior vena cava (IVC) routes at equivalent doses. In rats, AAV8-dTomato expression was primarily periportal across IHP, PV, and IVC routes, while in cynomolgus monkey, IHP delivery showed a pericentral pattern.
Conclusions
In this study, we found that IHP is an effective strategy for AAV8 delivery. In addition, the distribution characteristics of AAV8, when delivered in cynomolgus monkey via IHP, provide candidate vector delivery schemes for gene therapy for different types of genetic liver diseases.
7.Exploration of Clinical Thoughts for Treatment of Stable Angina with Insomnia under the Guidance of the "Blood-Pulse-Heart-Spirit"
Xinbiao FAN ; Zhipeng YAN ; Xiaofei GENG ; Lu LIAN ; Binbin DING ; Aolin LI ; Junping ZHANG
Journal of Traditional Chinese Medicine 2024;65(12):1240-1244
Guided by the concept of "blood-pulse-heart-spirit", it is believed that stable angina combined with insomnia is caused by disturbance of blood vessels, which leads to loss of nourishment for the heart body and heart spirit, so the core treatment principle is to regulate the blood vessels and calm the mind. At the beginning of the disease, it shows as the liver fails to govern the free flow of qi, and disorders qi and blood; during the progress of the disease, it shows as spleen deficiency and phlegm stagnation, phlegm and blood stasis obstructing the vessels; the central mechanism of the disease shows as disturbance of blood vessels and insufficient heart yin. For the pattern of liver depression and blood stasis, pattern of phlegm and blood stasis blocking the vessels, and pattern of heart yin deficiency, it is recommended to treat by Wuzang Shenning Formula (五脏神宁方) to dredge the liver and regulate the vessels, Banxia Houpo Decoction (半夏厚朴汤) plus Gualou Xiebai Banxia Decoction (瓜蒌薤白半夏汤) to dissolve phlegm and regulate the vessels, and Yunpi Tiaoxin Decoction (运脾调心汤) to nourish the yin and regulate the vessels. Throughout the treatment, pattern differentiation and treatment is accompanied by the method of calming the mind with heavy sedatives and nourishing the blood to calm the mind, so as to achieve the purpose of regulating mind and heart together and treating the body and spirit at the same time.
8.Preliminary study on the efficacy of subretinal injection of Aflibercept in the treatment of refractory polypoidal choroidal vasculopathy
Xiao YU ; Teng LIU ; Yuling ZOU ; Ziqing MAO ; Huimin FAN ; Zhiping CHEN ; Zhipeng YOU
Chinese Journal of Ocular Fundus Diseases 2024;40(2):122-128
Objective:To observe the efficacy and safety of subretinal injection of Aflibercept for the treatment of refractory or recurrent polypoidal choroidal vasculopathy (PCV).Methods:A prospective clinical research. From January to June 2022, 18 patients of 18 eyes with PCV diagnosed in The Affiliated Eye Hospital of Nanchang University were included in the study. All patients underwent best corrected visual acuity (BCVA), indocyanine green angiography and optical coherence tomography (OCT). The BCVA examination was performed using the international standard visual acuity chart, which was converted to logarithm of the minimum angle of resolution (logMAR) visual acuity during statistics. The large choroidal vessel thickness (LVCT), central retinal thickness (CRT), sub-foveal choroidal thickness (SFCT) and retinal pigment epithelium detachment (PED) height were measured by enhanced depth imaging technique of OCT. The choroidal vascular index (CVI) was calculated. There were 18 patients of 18 eyes, 11 males of 11 eyes and 7 females of 7 eyes. The age was (64.22±3.86) years old. The disease duration was (5.22±1.80) years. The patient had received intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs for (7.72±1.36) times. The logMAR BCVA of the affected eyes was 1.28±0.25. The SFCT, CRT, LVCT, PED height were (436.56±9.80), (432.44±44.29), (283.78±27.10), (342.44±50.18) μm, respectively, and CVI was 0.65±0.01. All eyes were treated with a single subretinal injection of 40 mg/ml Aflibercept 0.05 ml (including Aflibercept 2.0 mg). According to the results of OCT and BCVA after treatment, the lesions were divided into active type and static type. The active lesions were treated with intravitreal injection of Aflibercept at the same dose as before. Quiescent lesions were followed up. Examinations were performed 1-3, 6, 9 and 12 months after treatment using the same equipment and methods before treatment. The BCVA, LVCT, CRT, SFCT, PED height, CVI, interretinal or subretinal fluid, lesion regression rate, injection times, and complications during and after treatment were observed. The BCVA, SFCT, CRT, LVCT, PED height and CVI before and after treatment were compared by repeated measures analysis of variance.Results:Eighteen eyes received subretinal and/or intravitreal injection of Aflibercept (1.61±0.85) times (1-4 times). At the last follow-up, the polypoid lesions regressed in 4 eyes and PED disappeared in 1 eye. Compared with before treatment, BCVA ( F=50.298) gradually increased, CRT ( F=25.220), PED height ( F=144.16), SFCT ( F=69.77), LVCT ( F=136.69), CVI ( F=72.70) gradually decreased after treatment. The differences were statistically significant ( P<0.001). Macular hole occurred in 1 eye after treatment, and the hole closed spontaneously 3 months after treatment. No serious complications such as retinal tear, retinal detachment, endophthalmitis and vitreous hemorrhage occurred during and after treatment. Conclusion:Subretinal injection of Aflibercept is safe and effective in the treatment of refractory PCV.
9.Therapeutic effect of subretinal injection of alteplase plus Conbercept for acute submacular hemorrhage secondary to polypoid choroidal vasculopathy
Ziqing MAO ; Xiao YU ; Xifeng TIAN ; Huimin FAN ; Zhiping CHEN ; Yuling ZOU ; Zhipeng YOU
Chinese Journal of Ocular Fundus Diseases 2024;40(2):129-135
Objective:To observe the efficacy and safety of vitrectomy combined with subretinal injection of alteplase (tPA) and intravitreal injection of Conbercept in the treatment of large area submacular hemorrhage (SMH) secondary to polypoidal choroidal vasculopathy (PCV).Methods:A retrospective clinical study. From January to September 2021, 32 eyes of 32 patients with massive SMH secondary to PCV diagnosed in the Affiliated Eye Hospital of Nanchang University were included in the study. Large SMH was defined as hemorrhage diameter ≥4 optic disc diameter (DD). There were 32 patients (32 eyes), 20 males and 12 females. The mean age was (72.36±8.62) years. All patients had unilateral disease.The duration from onset of symptoms to treatment was (7.21±3.36) days. All patients underwent best corrected visual acuity (BCVA) and optical coherence tomography (OCT) examination. BCVA examination was performed using the international standard visual acuity chart, which was converted to the logarithm of the minimum angle of resolution (logMAR) visual acuity during statistics. The central macular thickness (CMT) was measured by spectral domain-OCT. The average size of SMH was (6.82±1.53) DD. The logMAR BCVA 1.73±0.44; CMT was (727.96±236.40) μm. All patients were treated with 23G pars plana vitrectomy combined with subretinal injection of tPA and intravitreal injection of Conbercept. At 1, 3, 6 and 12 months after treatment, the same equipment and methods were used for relevant examinations before treatment. The changes of BCVA and CMT, the clearance rate of macular hemorrhage, and the complications during and after surgery were observed. BCVA and CMT before and after treatment were compared by repeated measures analysis of variance.Results:Compared with before treatment, BCVA gradually increased at 1, 3, 6 and 12 months after treatment, and the differences were statistically significant ( F=77.402, P<0.001). There was no significant difference in BCVA between any two groups at different time points after treatment ( P>0.05). Correlation analysis showed that BCVA at 12 months after treatment was negatively correlated with the course of disease ( r=-0.053, P=0.774). One week after treatment, macular hemorrhage was completely cleared in 30 eyes (93.75%, 30/32). The CMT was (458.56±246.21), (356.18±261.46), (345.82±212.38) and (334.64±165.54) μm at 1, 3, 6 and 12 months after treatment, respectively. Compared with before treatment, CMT decreased gradually after treatment, and the difference was statistically significant ( F=112.480, P<0.001). There were statistically significant differences in different follow-up time before and after treatment ( P<0.001). The number of treatments combined with Conbercept during and after surgery was (4.2±1.8) times. At the last follow-up, there was no recurrence of SMH, retinal interlamellar effusion and other complications. Conclusion:Subretinal injection of tPA combined with intravitreal injection of Conbercept is safe and effective in the treatment of large SMH secondary to PCV, and it can significantly improve the visual acuity of patients.
10.Predictive value of changes in inflammatory markers for prognosis in patients with advanced non-small cell lung cancer treated with the first-line immunotherapy plus chemotherapy
Zhipeng FAN ; Jing YU ; Jing HU ; Zhengkai LIAO ; Yu XU ; Wen OUYANG ; Conghua XIE
Journal of International Oncology 2024;51(5):257-266
Objective:To investigate the correlation between pre- and post-treatment changing trends in peripheral blood inflammatory markers and efficacy and their predictive value for prognosis in non-small cell lung cancer (NSCLC) patients treated with the first-line immunotherapy plus chemotherapy.Methods:The clinical data of NSCLC patients admitted to the Department of Radiation and Chemotherapy for Lung Oncology, Zhongnan Hospital of Wuhan University from October 2018 to May 2023 were retrospectively analyzed. The χ2 test was used to analyze the correlation between the changing trend of peripheral blood inflammatory markers and the efficacy of immunotherapy plus chemotherapy. The influencing factors of objective response rate (ORR) were assessed using binary logistic regression analysis. Kaplan-Meier survival curve and Cox proportional hazards model were used to analyze the prognostic value of the changing trend of peripheral blood inflammation markers on patients' prognosis. Results:A total of 102 NSCLC patients treated with first-line immunotherapy plus chemotherapy were included. The proportion of patients with bone metastases was higher in the lymphocyte to monocyte ratio (LMR) decreased group ( n=50) than that in the increased group ( n=52) ( χ2=4.28, P=0.039), whereas the pathological type of patients in the platelet to lymphocyte ratio (PLR) decreased group ( n=51) was more common in squamous carcinoma compared to patients in the increased group ( n=51) ( χ2=18.99, P<0.001), and a higher proportion of patients in the prognostic nutritional index (PNI) decreased group ( n=46) was female than that in the increased group ( n=56) ( χ2=4.29, P=0.038), with statistically significant differences. The 2-cycle objective response rate (ORR) of patients in the LMR increased and decreased groups was 63.5% (33/52) and 44.0% (22/50) ( χ2=3.89, P=0.049), the 2-cycle ORR of patients in the neutrophil to lymphocyte ratio (NLR) increased ( n=24) and decreased ( n=78) groups was 29.2% (7/24) and 61.5% (48/78) ( χ2=7.74, P=0.005), and the 2-cycle ORR for patients in the systemic immune inflammatory index (SII) increased group ( n=27) and decreased group ( n=75) was 33.3% (9/27) and 61.3% (46/75) ( χ2=6.26, P=0.012), with statistically significant differences. Multivariate analysis showed that the changing trend of inflammatory markers in peripheral blood were not related to ORR. The Kaplan-Meier survival curve indicated that patients in the group with SII decreased had longer median progression-free survival (PFS) (not reached vs. 7.1 months, χ2=9.35, P=0.002) and median overall survival (OS) (not reached vs. 16.6 months, χ2=11.08, P<0.001) than those in the SII increased group, and patients in the NLR decreased group had longer median OS (not reached vs. 22.2 months, χ2=4.56, P=0.033) than that in the NLR increased group. Univariate analysis suggested that both brain and bone metastasis ( HR=4.04, 95% CI: 1.23-13.35, P=0.022), increased SII ( HR=2.83, 95% CI: 1.41-5.66, P=0.003) were found to be significant factors affecting the PFS of NSCLC patients, both brain and bone metastasis ( HR=3.47, 95% CI: 1.05-11.45, P=0.041), increased NLR ( HR=2.17, 95% CI: 1.05-4.51, P=0.037) and increased SII ( HR=3.12, 95% CI: 1.54-6.30, P=0.002) were found to be significant factors affecting the OS of NSCLC patients. Multivariate analysis demonstrated that both brain and bone metastasis ( HR=4.32, 95% CI: 1.30-14.40, P=0.017) and increased SII ( HR=2.89, 95% CI: 1.44-5.81, P=0.003) were independent risk factors for PFS in NSCLC patients, both brain and bone metastasis ( HR=3.76, 95% CI: 1.13-12.50, P=0.031) and increased SII ( HR=3.47, 95% CI: 1.28-9.41, P=0.014) remained independent risk factors for OS in patients with NSCLC. Conclusion:The changing trend of peripheral blood inflammatory markers of NSCLC patients cannot independently predict the efficacy of 2-cycle immunotherapy plus chemotherapy. Both brain and bone metastasis, as well as the changing trend of SII can be used as important indicators to predict PFS and OS in advanced NSCLC patients treated with first-line immunotherapy plus chemotherapy. The simultaneous occurrence of brain and bone metastasis and SII increased suggest poor prognosis of NSCLC patients.


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