1.Research progress of immune checkpoint inhibitors in the treatment of EGFR-TKIs-resistant NSCLC
Yixuan ZHU ; Yang WANG ; Tongmin WANG
China Pharmacy 2025;36(2):239-244
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are targeted drugs for the treatment of advanced non-small cell lung cancer (NSCLC), but long-term use inevitably leads to drug resistance. Resistance to EGFR-TKIs can alter the tumor microenvironment, and patients with NSCLC resistant to EGFR-TKIs can regain the benefits of immune checkpoint inhibitors (ICIs), but the changes in the tumor microenvironment are complex and the efficacy is unclear. This article reviews the clinical studies of ICIs in the treatment of EGFR-TKIs-resistant NSCLC, and finds that for patients with EGFR-TKIs-resistant NSCLC, the efficacy of ICIs as a single agent is unclear, and other relevant biomarkers need to be found to screen the beneficiary population. ICIs+EGFR-TKIs have potential toxicity and are not recommended for clinical use. There is controversy about the efficacy of ICIs+chemotherapy, and it is recommended to use it cautiously in clinical practice. ICIs+anti-vascular endothelial growth factor (VEGF) drug therapy has a synergistic effect, but may increase the incidence of adverse events. ICIs+chemotherapy+anti- VEGF drug have a synergistic effect and the incidence of adverse events is similar to that of chemotherapy. New ICIs such as lymphocyte activating gene 3 inhibitors are still in the clinical research stage or preclinical research stage, but they may be a new promising treatment.
2.Research progress of immune checkpoint inhibitors in the treatment of EGFR-TKIs-resistant NSCLC
Yixuan ZHU ; Yang WANG ; Tongmin WANG
China Pharmacy 2025;36(2):239-244
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are targeted drugs for the treatment of advanced non-small cell lung cancer (NSCLC), but long-term use inevitably leads to drug resistance. Resistance to EGFR-TKIs can alter the tumor microenvironment, and patients with NSCLC resistant to EGFR-TKIs can regain the benefits of immune checkpoint inhibitors (ICIs), but the changes in the tumor microenvironment are complex and the efficacy is unclear. This article reviews the clinical studies of ICIs in the treatment of EGFR-TKIs-resistant NSCLC, and finds that for patients with EGFR-TKIs-resistant NSCLC, the efficacy of ICIs as a single agent is unclear, and other relevant biomarkers need to be found to screen the beneficiary population. ICIs+EGFR-TKIs have potential toxicity and are not recommended for clinical use. There is controversy about the efficacy of ICIs+chemotherapy, and it is recommended to use it cautiously in clinical practice. ICIs+anti-vascular endothelial growth factor (VEGF) drug therapy has a synergistic effect, but may increase the incidence of adverse events. ICIs+chemotherapy+anti- VEGF drug have a synergistic effect and the incidence of adverse events is similar to that of chemotherapy. New ICIs such as lymphocyte activating gene 3 inhibitors are still in the clinical research stage or preclinical research stage, but they may be a new promising treatment.
3.Genotype and phenotype correlation analysis of retinitis pigmentosa-associated RHO gene mutation in a Yi pedigree
Yajuan ZHANG ; Hong YANG ; Hongchao ZHAO ; Dan MA ; Meiyu SHI ; Weiyi ZHENG ; Xiang WANG ; Jianping LIU
International Eye Science 2025;25(3):499-505
AIM: To delineate the specific mutation responsible for retinitis pigmentosa(RP)in a Yi pedigree, and to analyze the correlation of RHO gene mutation with clinical phenotype.METHODS:A comprehensive clinical evaluation was conducted on the proband diagnosed with RP and other familial members, complemented by a thorough ophthalmic examination. Peripheral blood samples were obtained from the proband and familial members, from which genomic DNA was extracte. Subsequent whole exome sequencing(WES)was employed to identify the variant genes in the proband. The identified variant gene was validated through Sanger sequencing, then an in-depth analysis of the mutation genes was carried out using genetic databases to ascertain the pathogenic mutation sites. Furthermore, an exhaustive analysis was performed to delineate the genotype and phenotype characteristics.RESULTS:The RP pedigree encompasses 5 generations with 42 members, including 19 males and 23 females. A total of 13 cases of RP were identified, consisting of 4 males and 9 females, which conforms to the autosomal dominant inheritance pattern. The clinical features of this family include an early onset age, rapid progression, and a more severe condition. The patients were found to have night blindness around 6 years old, representing the earliest reported case of night blindness in RP families. The retina was manifested by progressive osteocytoid pigmentation of the fundus, a reduced visual field, and significantly decreased or even vanished a and b amplitudes of ERG. The combined results of WES and Sanger sequencing indicated that the proband had a heterozygous missense mutation of the RHO gene c.1040C>T:p.P347L, where the 1 040 base C of cDNA was replaced by T, causing codon 347 to encode leucine instead of proline. Interestingly, this mutation has not been reported in the Chinese population.CONCLUSION:This study confirmed that the mutant gene of RP in a Yi nationality pedigree was RHO(c.1040C>T). This variant leads to the change of codon 347 from encoding proline to encoding leucine, resulting in a severe clinical phenotype among family members. This study provides a certain molecular, clinical, and genetic basis for genetic counseling and gene diagnosis of RHO.
4.Genotype and phenotype correlation analysis of retinitis pigmentosa-associated RHO gene mutation in a Yi pedigree
Yajuan ZHANG ; Hong YANG ; Hongchao ZHAO ; Dan MA ; Meiyu SHI ; Weiyi ZHENG ; Xiang WANG ; Jianping LIU
International Eye Science 2025;25(3):499-505
AIM: To delineate the specific mutation responsible for retinitis pigmentosa(RP)in a Yi pedigree, and to analyze the correlation of RHO gene mutation with clinical phenotype.METHODS:A comprehensive clinical evaluation was conducted on the proband diagnosed with RP and other familial members, complemented by a thorough ophthalmic examination. Peripheral blood samples were obtained from the proband and familial members, from which genomic DNA was extracte. Subsequent whole exome sequencing(WES)was employed to identify the variant genes in the proband. The identified variant gene was validated through Sanger sequencing, then an in-depth analysis of the mutation genes was carried out using genetic databases to ascertain the pathogenic mutation sites. Furthermore, an exhaustive analysis was performed to delineate the genotype and phenotype characteristics.RESULTS:The RP pedigree encompasses 5 generations with 42 members, including 19 males and 23 females. A total of 13 cases of RP were identified, consisting of 4 males and 9 females, which conforms to the autosomal dominant inheritance pattern. The clinical features of this family include an early onset age, rapid progression, and a more severe condition. The patients were found to have night blindness around 6 years old, representing the earliest reported case of night blindness in RP families. The retina was manifested by progressive osteocytoid pigmentation of the fundus, a reduced visual field, and significantly decreased or even vanished a and b amplitudes of ERG. The combined results of WES and Sanger sequencing indicated that the proband had a heterozygous missense mutation of the RHO gene c.1040C>T:p.P347L, where the 1 040 base C of cDNA was replaced by T, causing codon 347 to encode leucine instead of proline. Interestingly, this mutation has not been reported in the Chinese population.CONCLUSION:This study confirmed that the mutant gene of RP in a Yi nationality pedigree was RHO(c.1040C>T). This variant leads to the change of codon 347 from encoding proline to encoding leucine, resulting in a severe clinical phenotype among family members. This study provides a certain molecular, clinical, and genetic basis for genetic counseling and gene diagnosis of RHO.
5.Influencing factors for recompensation in patients with decompensated hepatitis C cirrhosis
Danqing XU ; Huan MU ; Yingyuan ZHANG ; Lixian CHANG ; Yuanzhen WANG ; Weikun LI ; Zhijian DONG ; Lihua ZHANG ; Yijing CHENG ; Li LIU
Journal of Clinical Hepatology 2025;41(2):269-276
ObjectiveTo investigate the influencing factors for recompensation in patients with decompensated hepatitis C cirrhosis, and to establish a predictive model. MethodsA total of 217 patients who were diagnosed with decompensated hepatitis C cirrhosis and were admitted to The Third People’s Hospital of Kunming l from January, 2019 to December, 2022 were enrolled, among whom 63 patients who were readmitted within at least 1 year and had no portal hypertension-related complications were enrolled as recompensation group, and 154 patients without recompensation were enrolled as control group. Related clinical data were collected, and univariate and multivariate analyses were performed for the factors that may affect the occurrence of recompensation. The independent-samples t test was used for comparison of normally distributed measurement data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed measurement data between two groups; the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. A binary Logistic regression analysis was used to investigate the influencing factors for recompensation in patients with decompensated hepatitis C cirrhosis, and the receiver operating characteristic (ROC) curve was used to assess the predictive performance of the model. ResultsAmong the 217 patients with decompensated hepatitis C cirrhosis, 63 (29.03%) had recompensation. There were significant differences between the recompensation group and the control group in HIV history (χ2=4.566, P=0.034), history of partial splenic embolism (χ2=6.687, P=0.014), Child-Pugh classification (χ2=11.978, P=0.003), grade of ascites (χ2=14.229, P<0.001), albumin (t=4.063, P<0.001), prealbumin (Z=-3.077, P=0.002), high-density lipoprotein (t=2.854, P=0.011), high-sensitivity C-reactive protein (Z=-2.447, P=0.014), prothrombin time (Z=-2.441, P=0.015), carcinoembryonic antigen (Z=-2.113, P=0.035), alpha-fetoprotein (AFP) (Z=-2.063, P=0.039), CA125 (Z=-2.270, P=0.023), TT3 (Z=-3.304, P<0.001), TT4 (Z=-2.221, P=0.026), CD45+ (Z=-2.278, P=0.023), interleukin-5 (Z=-2.845, P=0.004), tumor necrosis factor-α (Z=-2.176, P=0.030), and portal vein width (Z=-5.283, P=0.005). The multivariate analysis showed that history of partial splenic embolism (odds ratio [OR]=3.064, P=0.049), HIV history (OR=0.195, P=0.027), a small amount of ascites (OR=3.390, P=0.017), AFP (OR=1.003, P=0.004), and portal vein width (OR=0.600, P<0.001) were independent influencing factors for the occurrence of recompensation in patients with decompensated hepatitis C cirrhosis. The ROC curve analysis showed that HIV history, grade of ascites, history of partial splenic embolism, AFP, portal vein width, and the combined predictive model of these indices had an area under the ROC curve of 0.556, 0.641, 0.560, 0.589, 0.745, and 0.817, respectively. ConclusionFor patients with decompensated hepatitis C cirrhosis, those with a history of partial splenic embolism, a small amount of ascites, and an increase in AFP level are more likely to experience recompensation, while those with a history of HIV and an increase in portal vein width are less likely to experience recompensation.
6.Factors affecting Pomacea distribution and prediction of suitable distribution areas of Pomacea in Dali Bai Autonomous Prefecture of Yunnan Province
Zhongqiu LI ; Yuhua LIU ; Yunhai GUO ; Zixin WEI ; Junhu CHEN ; Qiang WANG ; Tianmei LI ; Shizhu LI
Chinese Journal of Schistosomiasis Control 2025;37(1):69-75
Objective To investigate the factors affecting the distribution of Pomacea and project the trends in the spread of suitable distribution areas of Pomacea in 2050 and 2070 in Dali Bai Autonomous Prefecture, so as to provide insights into Pomacea control in the prefecture. Methods The longitudes and latitudes of Pomacea sampling sites were captured based on Pomacea field survey data in 12 cities (counties) of Dali Bai Autonomous Prefecture from 2023 to 2024. A total of 19 climatic factors (annual mean temperature, mean diurnal range, isothermality, temperature seasonality, maximum temperature of the warmest month, minimum temperature of the coldest month, temperature annual range, mean temperature of the wettest quarter, mean temperature of the driest quarter, mean temperature of the warmest month, mean temperature of the coldest month, annual precipitation, precipitation of the wettest month, precipitation of the driest month, precipitation seasonality, precipitation of the wettest quarter, precipitation of the driest quarter, mean temperature of the warmest quarter, and mean temperature of the coldest quarter) and representative concentration pathways (RCPs) were retrieved from the world climate database (www.worldclim.org). All climatic variables were employed to create a maximum entropy (MaxEnt) model. The predictive accuracy of the model was assessed with the area under the receiver operating characteristic (ROC) curve (AUC), and the contributions of these 19 climatic factors to the distribution of Pomacea were analyzed in Dali Bai Autonomous Prefecture using Jackknife test. In addition, the suitable distribution areas of Pomacea were predicted with the MaxEnt model in Dali Bai Autonomous Prefecture in 2024 and in 2050 and 2070 under RCP4.5. Results Data pertaining to 91 Pomacea sampling sites were captured. ROC analysis revealed the MaxEnt model had an AUC value of 0.885 ± 0.088 for predicting the suitable distribution areas of Pomacea in Dali Bai Autonomous Prefecture. Of the 19 climatic factors, the maximum temperature of the warmest month had the highest contribution to the distribution of Pomacea in Dali Bai Autonomous Prefecture, followed by mean temperature of the driest quarter, mean temperature of the wettest quarter and minimum temperature of the coldest month. The suitable distribution area of Pomacea was predicted to be 14 555.69 km2 in Dali Bai Autonomous Prefecture in 2024, and would expand gradually to the southeastern part of the prefecture in the future due to climatic factors. The suitable distribution areas of Pomacea were projected to expand to 21 475.61 km2 in 2050 and 25 782.52 km2 in 2070 in Dali Bai Autonomous Prefecture, respectively. Conclusions Temperature is an important contributor to the distribution of Pomacea in Dali Bai Autonomous Prefecture, and the suitable distribution area of Pomacea will gradually expand to the southeastern part of the prefecture in 2050 and 2070.
7.Value of FibroScan, gamma-glutamyl transpeptidase-to-platelet ratio, S index, interleukin-6, and tumor necrosis factor-α in the diagnosis of HBeAg-positive chronic hepatitis B liver fibrosis
Yingyuan ZHANG ; Danqing XU ; Huan MU ; Chunyan MOU ; Lixian CHANG ; Yuanzhen WANG ; Hongyan WEI ; Li LIU ; Weikun LI ; Chunyun LIU
Journal of Clinical Hepatology 2025;41(4):670-676
ObjectiveTo investigate the value of noninvasive imaging detection (FibroScan), two serological models of gamma-glutamyl transpeptidase-to-platelet ratio (GPR) score and S index, and two inflammatory factors of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in predicting liver fibrosis in patients with HBeAg-positive chronic hepatitis B (CHB), as well as the consistency of liver biopsy in pathological staging, and to provide early warning for early intervention of CHB. MethodsA retrospective analysis was performed for 131 HBeAg-positive CHB patients who underwent liver biopsy in The Third People’s Hospital of Kunming from January 2019 to December 2023. The results of liver biopsy were collected from all patients, and related examinations were performed before liver biopsy, including total bilirubin, alanine aminotransferase, platelet count, gamma-glutamyl transpeptidase, albumin, IL-6, TNF-α, liver stiffness measurement (LSM), and abdominal ultrasound. An analysis of variance was used for comparison of normally distributed continuous data between groups, and the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups. A Kappa analysis was used to investigate the consistency between LSM noninvasive histological staging and pathological staging based on liver biopsy, and the Spearman analysis was used to investigate the correlation between each variable and FibroScan in the diagnosis of liver fibrosis stage. The Logistic regression analysis was used to construct joint predictive factors. The receiver operating characteristic (ROC) curve was used to evaluate the value of each indicator alone and the joint predictive model in the diagnosis of liver fibrosis, and the Delong test was used for comparison of the area under the ROC curve (AUC). ResultsIn the consistency check, inflammation degree based on liver biopsy had a Kappa value of 0.807 (P<0.001), and liver fibrosis degree based on liver biopsy had a Kappa value of 0.827 (P<0.001), suggesting that FibroScan noninvasive histological staging and liver biopsy showed good consistency in assessing inflammation degree and liver fibrosis stage. Age was positively correlated with LSM, GPR score, S index, IL-6, and TNF-α (all P<0.05), and GPR score, S index, IL-6, and TNF-α were positively correlated with LSM (all P<0.05). GPR score, S index, IL-6, and TNF-α were all independent risk factors for diagnosing significant liver fibrosis (≥S2) and progressive liver fibrosis (≥S3) (all P<0.05). As for each indicator alone, GPR score had the highest value in the diagnosis of significant liver fibrosis (≥S2), followed by S index, IL-6, and TNF-α, while S index had the highest value in the diagnosis of progressive liver fibrosis (≥S3), followed by GPR score, TNF-α, and IL-6. The joint model had a higher predictive value than each indicator alone (all P<0.05). ConclusionThere is a good consistency between FibroScan noninvasive histological staging and pathological staging based on liver biopsy. GPR score, S index, IL-6, and TNF-α are independent risk factors for evaluating different degree of liver fibrosis in CHB, and the combined prediction model established by them can better diagnose liver fibrosis.
8.BIRC5 Is a Potential Biomarker Associated with Immune System Infiltration in Glioma
Xitong YANG ; Yuanyuan ZHANG ; Fuhui DUAN ; Siying LI ; Guangming WANG
Journal of Korean Neurosurgical Society 2025;68(2):184-201
Objective:
: Baculovirus inhibitory of apoptosis repeat-containing 5 (BIRC5) is critically implicated in various types of tumors. However, the specific mechanisms by which it operates in glioma are yet to be fully understood.
Methods:
: The data sourced from The Cancer Genome Atlas and Gene Expression Omnibus were merged and analyzed using the R software to investigate the relationship between BIRC5 expression and prognosis and diagnosis outcomes. This exploration was conducted utilizing various biological information repositories. The correlation between BIRC5 and immunity was obtained based on TIMER and TISIDB databases.
Results:
: Gliomas displayed a markedly elevated level of BIRC5 expression compared to adjacent tissues. Patients with glioma who exhibit elevated levels of BIRC5 experience poorer prognoses and shorter survival times. Subgroup classification further revealed that heightened expression of BIRC5 led to diminished overall survival. Analysis of logistic regression and COX indicated that expression of BIRC5 serves as a risk factor in glioma development. Functional enrichment pathways showed that the 72 hub genes related to BIRC5 were mainly closely related to nuclear division, spindle, tubulin binding, and cell cycle in glioma patients. BBIRC5 methylation suggested that BIRC5 might influence the immune response regulation and the tumor microenvironment within gliomas. BIRC5 is associated with many chemicals. Additionally, studies conducted using cell experiments and pathological sections have consistently shown that BIRC5 expression is higher in tumor cells compared to normal cells and tissues.
Conclusion
: BIRC5 holds promise as a valuable tool in the diagnosis, prognosis, and management of gliomas.
9.BIRC5 Is a Potential Biomarker Associated with Immune System Infiltration in Glioma
Xitong YANG ; Yuanyuan ZHANG ; Fuhui DUAN ; Siying LI ; Guangming WANG
Journal of Korean Neurosurgical Society 2025;68(2):184-201
Objective:
: Baculovirus inhibitory of apoptosis repeat-containing 5 (BIRC5) is critically implicated in various types of tumors. However, the specific mechanisms by which it operates in glioma are yet to be fully understood.
Methods:
: The data sourced from The Cancer Genome Atlas and Gene Expression Omnibus were merged and analyzed using the R software to investigate the relationship between BIRC5 expression and prognosis and diagnosis outcomes. This exploration was conducted utilizing various biological information repositories. The correlation between BIRC5 and immunity was obtained based on TIMER and TISIDB databases.
Results:
: Gliomas displayed a markedly elevated level of BIRC5 expression compared to adjacent tissues. Patients with glioma who exhibit elevated levels of BIRC5 experience poorer prognoses and shorter survival times. Subgroup classification further revealed that heightened expression of BIRC5 led to diminished overall survival. Analysis of logistic regression and COX indicated that expression of BIRC5 serves as a risk factor in glioma development. Functional enrichment pathways showed that the 72 hub genes related to BIRC5 were mainly closely related to nuclear division, spindle, tubulin binding, and cell cycle in glioma patients. BBIRC5 methylation suggested that BIRC5 might influence the immune response regulation and the tumor microenvironment within gliomas. BIRC5 is associated with many chemicals. Additionally, studies conducted using cell experiments and pathological sections have consistently shown that BIRC5 expression is higher in tumor cells compared to normal cells and tissues.
Conclusion
: BIRC5 holds promise as a valuable tool in the diagnosis, prognosis, and management of gliomas.
10.BIRC5 Is a Potential Biomarker Associated with Immune System Infiltration in Glioma
Xitong YANG ; Yuanyuan ZHANG ; Fuhui DUAN ; Siying LI ; Guangming WANG
Journal of Korean Neurosurgical Society 2025;68(2):184-201
Objective:
: Baculovirus inhibitory of apoptosis repeat-containing 5 (BIRC5) is critically implicated in various types of tumors. However, the specific mechanisms by which it operates in glioma are yet to be fully understood.
Methods:
: The data sourced from The Cancer Genome Atlas and Gene Expression Omnibus were merged and analyzed using the R software to investigate the relationship between BIRC5 expression and prognosis and diagnosis outcomes. This exploration was conducted utilizing various biological information repositories. The correlation between BIRC5 and immunity was obtained based on TIMER and TISIDB databases.
Results:
: Gliomas displayed a markedly elevated level of BIRC5 expression compared to adjacent tissues. Patients with glioma who exhibit elevated levels of BIRC5 experience poorer prognoses and shorter survival times. Subgroup classification further revealed that heightened expression of BIRC5 led to diminished overall survival. Analysis of logistic regression and COX indicated that expression of BIRC5 serves as a risk factor in glioma development. Functional enrichment pathways showed that the 72 hub genes related to BIRC5 were mainly closely related to nuclear division, spindle, tubulin binding, and cell cycle in glioma patients. BBIRC5 methylation suggested that BIRC5 might influence the immune response regulation and the tumor microenvironment within gliomas. BIRC5 is associated with many chemicals. Additionally, studies conducted using cell experiments and pathological sections have consistently shown that BIRC5 expression is higher in tumor cells compared to normal cells and tissues.
Conclusion
: BIRC5 holds promise as a valuable tool in the diagnosis, prognosis, and management of gliomas.

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