1.Study on the apoptosis-inducing effect of esculetin on acute myeloid leukemia HL-60 cells via regulating the AKT/SKP2/MTH1 pathway
Weihua SONG ; Fuying CHU ; Wei XIE ; Jinliang CHEN ; Ping ZHAO ; Hong QIU ; Jian TAO ; Xiang CHEN
China Pharmacy 2026;37(1):36-41
OBJECTIVE To investigate the apoptosis-inducing effect of esculetin (Esc) on acute myeloid leukemia (AML) HL-60 cells by regulating the protein kinase B (AKT)/S-phase kinase-associated protein 2 (SKP2)/MutT homolog 1 (MTH1) pathway. METHODS AML HL-60 cells were randomly divided into control group (routine culture), Esc low-concentration group (L-Esc group, 25 μmol/L Esc), Esc medium-concentration group (M-Esc group, 50 μmol/L Esc), Esc high-concentration group (H-Esc group, 100 μmol/L Esc), and high-concentration of Esc+ SC79 (AKT agonist) group (100 μmol/L Esc+5 μmol/L SC79). Cell proliferation in each group was detected by MTT assay and colony formation assay. The level of reactive oxygen species (ROS) in cells was measured by using the CM-H2DCFDA fluorescent probe. Cell apoptosis was analyzed by flow cytometry. Western blot assay was performed to detect the expression levels of apoptosis-related proteins [B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), cleaved caspase-3], AKT/SKP2/MTH1 pathway-related proteins (p-AKT, AKT, SKP2, MTH1), along with the upstream and downstream proteins of AKT phosphatidylinositol 3-kinase (PI3K), cyclin-dependent kinase inhibitor 1 (P21) and cyclin-dependent kinase inhibitor 1B (P27). RESULTS Compared with control group, the cell viability, colony number, and the phosphorylation levels of AKT and PI3K proteins as well as protein expressions of SKP2, MTH1 and Bcl-2 were significantly decreased (P<0.05), while ROS level, apoptosis rate, and the expression levels of Bax, cleaved caspase-3, P21 and P27 proteins were significantly increased (P<0.05). Moreover, the effects of Esc exhibited concentration-dependence (P<0.05). Compared with H-Esc group, above indexes of high-concentration of Esc+ SC79 group were reversed significantly (P<0.05). CONCLUSIONS Esc may promote massive ROS production and induce activation of apoptosis in HL-60 cells by inhibiting the AKT/SKP2/MTH1 pathway, thus inhibiting the proliferation of HL-60 cells.
2.Differences in deltamethrin resistance and kdr gene mutation in Culex tritaeniorhynchus population in and outside the Yellow Sea wetland
Xiao-er ZHANG ; Zhi-ming WU ; Ye TIAN ; Qian CUI ; Yu-qian JI ; Huan WANG ; Shu-juan YANG ; Yi-chao ZHAO ; Yu WANG ; Hua-yu YIN ; Yu DING ; Guo-jin YAN ; Min-sen ZHAO ; Shou-gang ZHANG ; Bing-dong SONG ; Hong-na CHEN ; Jian GAO ; Wei-fang YANG ; Yu-fu ZHANG ; Hui LIU ; Hong-liang CHU
Acta Parasitologica et Medica Entomologica Sinica 2026;33(2):101-107
Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.
3.Mosquito surveillance and pathogen detection analysis in Jiangsu Province from 2020 to 2024
Jian GAO ; Hong-na CHEN ; Zhi-ming WU ; Wei-fang YANG ; Hong-liang CHU
Acta Parasitologica et Medica Entomologica Sinica 2026;33(3):187-191,203
Objective To analyze mosquito species composition and prevalence of pathogens carried by mosquitoes in Jiangsu Province from 2020 to 2024 and to provide a scientific basis for the prevention and control of mosquito-borne diseases. Methods Mosquitoes were collected using CO2-baited traps. The presence of mosquito-borne pathogens including dengue virus, Japanese encephalitis virus, yellow fever virus, West Nile virus, Chikungunya virus, and Sindbis virus was tested using commercial kits for fluorescence-based quantitative PCR. Results The most prevalent mosquito species found across different regions of Jiangsu Province were Culex pipiens pallens and Cx. tritaeniorhynchus, accounting for 81.35% to 93.01% of the total, followed by Armigeres subalbatus and Anopheles sinensis, which comprised 5.89% to 15.85% of the total. The densities of other monitored mosquito species were relatively low. Pathogen detection revealed that, only Cx. tritaeniorhynchus tested positive for Japanese encephalitis virus nucleic acid, whereas the remaining four mosquito species tested negative for the nucleic acids of all other six pathogens. The overall positivity rate of Japanese encephalitis virus (JEV) in Cx. tritaeniorhynchus showed an initially increasing trend followed by a decrease and a subsequent increase. The peak detection rate occurred in 2021 (11.93%), with a much lower positive rate of 0.80% in 2023. Genotyping result revealed that all JEV strains in Jiangsu Province belonged to the G1 genotype and were genetically closest to the strain Shangdong08DY.29 (MN072875.1). Conclusions The incidence of Japanese encephalitis virus carried by mosquito, especially Cx. tritaeniorhynchus, in Jiangsu Province shows an upward trend, requiring sustained surveillance. A variety of monitoring method should be adopted to survey mosquitoes across different habitats, ensuring the accuracy and comprehensiveness of the monitoring result.
4.Investigations of tick habitats and potential pathogens carried in urban environments of Jiangsu Province
Zhi-ming WU ; Ye TIAN ; Wei-fang YANG ; Hong-na CHEN ; Jian GAO ; Hui LIU ; Yu-fu ZHANG ; Gan CAO ; Hong-liang CHU
Acta Parasitologica et Medica Entomologica Sinica 2026;33(3):192-197
Objective To investigate the species composition, distribution, density, and pathogen-carrying status of host-seeking ticks in urban environments of Jiangsu Province, and to provide a scientific basis for the prevention and control of tick-borne diseases in urban settings. Methods From April to September 2023, a survey on host-seeking ticks was conducted in three types of habitats (city parks, residential areas, and street greenbelts) across 54 counties (cities, districts) of 13 prefecture-level cities in Jiangsu Province by using the flagging method. RStudio 4.4.3 (Windows version) was employed to perform chi-square test analysis on the species composition of ticks across different months, and Friedman test (for multiple paired samples) was applied to analyze monthly changes in the average tick density index among different habitats. Quantitative real-time PCR was performed to detect pathogens in the captured ticks. Results A total of 863 host-seeking ticks were captured from 54 habitats in 24 counties (cities, districts) of 11 prefecture-level cities (Nanjing, Wuxi, Changzhou, Suzhou, Nantong, Huai'an, Yancheng, Yangzhou, Zhenjiang, Taizhou, and Suqian) in Jiangsu Province, whereas no ticks were captured in Xuzhou and Lianyungang. The collected ticks belonged to three species, with Haemaphysalis longicornis being the dominant species (accounting for 82.62%), followed by Haemaphysalis flava and Hae. phasiana. The average density index of ticks in positive habitats was 3.20 ticks/ (flag·100 m). In terms of tick density among prefecture-level cities, Wuxi had the highest density[13.55 ticks/(flag·100 m)], whereas Nanjing and Taizhou had the lowest[both,0.20 ticks/(flag·100 m)]. With respect to the types of positive habitats,46 positive city parks,7 positive residential areas, and 1 positive street greenbelt were found, with the average tick density index being 3.46, 1.86, and 3.60 ticks/flag · 100 m, respectively. No statistically significant differences were observed in the monthly variations in the average tick density index among different habitats (P>0.05). Pathogen detection showed no Bandavirus dabieense, Rickettsia, or Borrelia burgdorferi in the collected ticks. Conclusions Host-seeking ticks have established populations in urban environments across most prefecture-level cities in Jiangsu Province, with Hae. longicornis identified as the dominant species. City parks serve as the primary breeding habitats for these ticks. Strengthening tick surveillance and control measures in densely populated and frequently visited areas, such as city parks and residential neighborhoods, is crucial for the effective prevention and control of urban tick-borne diseases.
5.Adrenocortical carcinoma with rhabdoid features: a case report and literature review
Mingchuan CHU ; Huimin SUN ; Hao WANG ; Jian SONG ; Yongshun GUO
Journal of Modern Urology 2025;30(1):64-68
[Objective] To investigate and summarize the clinicopathological features, diagnosis, treatment and prognosis of adrenocortical carcinoma with rhabdoid features. [Methods] The clinical diagnosis and treatment of a case of adrenocortical carcinoma with rhabdoid features admitled to Department of Urology, Weifang People's Hospital were reported.The clinical manifestations, pathological features, diagnosis and prognosis of the disease were analyzed in combination with relevant literature. [Results] A 34-year-old male patient was admitted due to scrotal distension and pain that had persisted for 6 months.Imaging examination showed a huge soft tissue tumor in the left adrenal region of the retroperitoneum with compression displacement of the left kidney, leading to obstruction of venous return in the left spermatic vein, which in turn caused varicose veins.The levels of serum renin, angiotensin, aldosterone, cortisol, and catecholamine were within normal ranges.Surgical resection of the tumor was performed, and postoperative pathological examination revealed that the tumor tissue was predominantly composed of rhabdoid cells, exhibiting positive immunohistochemical staining for INI 1, Syn, Calretinin and Vimentin.Genetic testing did not identify any deletion of SMARCB1 and SMARCA4 mutations.Therefore, the diagnosis was adrenocortical carcinoma with rhabdoid features.At the current 20-month follow-up, no recurrence or metastasis was observed.A review of the literature found that only 7 cases of this disease had been reported. [Conclusion] Adrenocortical carcinoma with rhabdoid features is a rare disease, and a definitive diagnosis is dependent upon pathological examination.Surgical resection remains the primary treatment.Long-term follow-up is essential, and further research is needed to evaluate the impact of adjuvant therapy.
6.Research progress of natural bioactive products in resisting loss of skin collagen
Chu-juan HU ; Lu-lu WANG ; Jian-dong JIANG ; Rui LI
Acta Pharmaceutica Sinica 2025;60(2):269-279
As the biggest tissue of human body, skin is the first barrier of resisting external aggression. Collagen is one of important parts of the skin, which could not only affect the aesthetics of skin, but also influence the health and normal function of skin. It is the great significance to find ways that could inhibit the loss of collagen. The mechanisms of the collagen degradation in skin are complex and multifaceted. Natural bioactive products have unique advantages in treating the loss of collagen, which have multi-targets and mechanisms. In this review, the mechanisms of skin collagen degradation are discussed, and the research progress of natural bioactive products in resisting skin aging through promoting collagen synthesis are reviewed, in order to provide references for futural research.
7.Direct and Indirect Effects of Prolonged Exposure to Long Working Hours on Risk Stroke Subtypes in the CONSTANCES Cohort
Marc FADEL ; Grace SEMBAJWE ; Jian LI ; Annette LECLERC ; Fernando PICO ; Alexis SCHNITZLER ; Eric Richard FADEL ; Yves ROQUELAURE ; Alexis DESCATHA
Journal of Stroke 2025;27(1):154-157
8.Diagnosis and treatment guideline for acute cervical spinal cord injury without fracture-dislocation in adults (version 2025)
Qingde WANG ; Tongwei CHU ; Jian DONG ; Liangjie DU ; Haoyu FENG ; Shunwu FAN ; Shiqing FENG ; Yanzheng GAO ; Yong HAI ; Da HE ; Dianming JIANG ; Jianyuan JIANG ; Bin LIN ; Bin LIU ; Baoge LIU ; Fang LI ; Feng LI ; Li LI ; Weishi LI ; Fangcai LI ; Xiaoguang LIU ; Hongjian LIU ; Yong LIU ; Zhongjun LIU ; Shibao LU ; Xuhua LU ; Keya MAO ; Xuexiao MA ; Yong QIU ; Limin RONG ; Jun SHU ; Yueming SONG ; Tiansheng SUN ; Yan WANG ; Zhe WANG ; Zheng WANG ; Bing WANG ; Linfeng WANG ; Yu WANG ; Qinghe WANG ; Jigong WU ; Hong XIA ; Guoyong YIN ; Jinglong YAN ; Wen YUAN ; Yong YANG ; Qiang YANG ; Cao YANG ; Jie ZHAO ; Jianguo ZHANG ; Yue ZHU ; Zezhang ZHU ; Yingjie ZHOU ; Zhongmin ZHANG ; Yan ZENG ; Dingjun HAO ; Baorong HE ; Wei MEI
Chinese Journal of Trauma 2025;41(3):243-252
Cervical spinal cord injury without fracture-dislocation (CSCIWFD) is referred to as a special type of cervical spinal cord injury characterized by traumatic spinal cord dysfunction and no significant bony structural abnormalities on imagines. Duo to the high risk of missed diagnosis during the initial consultation, CSCIWFD may lead to progressive neurological deterioration or even complete paralysis, severely impacting patients′ prognosis. Currently, there are no established consensuses over the diagnosis and treatment of CSCIWFD, such as the lack of evidence-based standards for indications of non-surgical treatment and risk of secondary neurological injury, as well as debates over the optimal timing for surgical intervention and indications for different surgical approaches. To address these issues, the Spine Trauma Group of the Orthopedic Branch of the Chinese Medical Doctor Association organized experts in the relevant fields to formulate Diagnosis and treatment guideline for acute cervical spinal cord injury without fracture- dislocation in adults ( version 2025) . Based on evidence-based medicine and the principles of scientific rigor and clinical applicability, the guidelines proposed 11 recommendations covering terminology, diagnosis, evaluation treatment, and rehabilitation, etc., aiming to standardize the management of CSCIWFD.
9.Exploration on the Onset of Acute Lymphoblastic Leukemia in Children Based on the Five-Circuit and Six-Qi Theory
Yunyun SUN ; Liang LI ; Leilei CHU ; Ke YANG ; Zhexiu JIANG ; Tian LIU ; Jianmin ZHANG ; Jian PAN ; Yanfang TAO
Journal of Guangzhou University of Traditional Chinese Medicine 2025;42(1):32-38
Objective To explore the five-circuit and six-qi features of birth time and onset time of children with acute lymphoblastic leukemia(ALL).Methods A total of 877 cases of children with ALL from Children's Hospital of Soochow University from June 2021 to February 2023 were collected,and their five-circuit and six-qi features of birth time and onset time were analyzed.And then the correlation of five-circuit and six-qi features of birth time and onset time with ALL was explored preliminarily,and the pathogenic characteristics of congenital factors and acquired pathogenic factors were revealed.Results(1)The children who were born in the year with the heavenly stems being bing(the 3rd of the ten heavenly stems)and ding(the 4th of the ten heavenly stems)and with the earthly branches being shen(the 8th of the twelve earthly branches)and you(the 9th of the twelve earthly branches)are prone to suffer from ALL,and the birth year of children with ALL had the five-circuit and six-qi features of the joining of guest circuit with dominant circuit being rebellious.ALL is commonly seen in the year with the heavenly stems being geng(the 7th of the ten heavenly stems)and xin(the 8th of the ten heavenly stems)and with the earthly branches being zi(the 1st of the twelve earthly branches)and chou(the 2nd of the twelve earthly branches),and the onset year of ALL in children had the five-circuit and six-qi features of the yearly circuit being gold-circuit and water-circuit,sitian-zaiquan yearly circuit qi being shaoyin monarch-fire with yangming dryness-gold,taiyin damp-earth with taiyang cold-water,and the qi-circuit assimilation relationship being celestial correspondence,same celestial correspondence,celestial correspondence in convergent year,disharmony,mildly-rebellious,and celestial restriction.Conclusion Gold-dryness and water-cold are the congenital factors and acquired pathogenic factors of ALL.The onset of ALL in children is closely related to qi insufficiency and qi stagnation of wood and fire in five-circuit and six-qi theory.
10.CMTM3 regulates proliferation and migration of glioblastoma U251 cells via the NF-κB signaling pathway
Lishi JIANG ; Wei TENG ; Wenjin QIU ; Yuanguo LING ; Xueping SHI ; Niya LONG ; Liangzhao CHU ; Jian LIU
Chinese Journal of Oncology 2025;47(2):136-148
Objective:To explore the effects and potential mechanisms of chemokine-like factor-like MARVEL transmembrane domain-containing Protein 3 (CMTM3) on the proliferation and migration of glioblastoma (GBM) cells.Methods:Using CMTM3 expression data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, we analyzed the differential expression of CMTM3 in GBM tissues and its impact on the prognosis of GBM patients. Immunohistochemical staining and protein content determination of CMTM3 was performed on GBM and adjacent non-cancerous tissue samples from 11 GBM patients who underwent surgical treatment at the Affiliated Hospital of Guizhou Medical University between November 3, 2022 and March 15, 2023. Additionally, the expression of CMTM3 was validated in GBM cell lines U87, U251, LN229, and the human astrocyte (NHA) cell line using real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot analyses. Stable cell lines with silenced and overexpressed CMTM3 (sh-CMTM3 group and OE-CMTM3 group) were constructed using U251 cells. The effect of CMTM3 expression on cell proliferation was assessed using the Cell Counting Kit-8 (CCK-8) assay. Flow cytometry was employed to examine the impact of CMTM3 expression on the cell cycle. Transwell assays were conducted to evaluate the influence of CMTM3 expression on cell migration. Bioinformatics analysis, Western blotting, NF-κB activation-nuclear translocation assays, and the NF-κB pathway inhibitor pyrrolidine dithiocarbamate ammonium (PDTC) were used to validate the effect of CMTM3 on the NF-κB pathway. Finally, a subcutaneous tumorigenesis assay in nude mice was performed to observe the impact of CMTM3 expression on the in vivo growth of U251 cells. Results:Bioinformatics analysis revealed that CMTM3 is highly expressed in GBM tissues. Patients with a high CMTM3 expression had lower overall survival (OS) and disease-free survival (DFS) rates compared with those with a low CMTM3 expression (with P values of 0.010 and 0.032, respectively). Among the 11 GBM pathological specimens, 10 samples exhibited higher CMTM3 protein expression levels in the cancerous tissue compared with the adjacent non-cancerous tissue. The average CMTM3 protein expression in these samples was 0.44±0.09, significantly higher than that in the adjacent non-cancerous tissues (0.12±0.02, P<0.001). In one sample, the difference in CMTM3 protein expression between the cancerous and adjacent non-cancerous tissues was not statistically significant ( P=0.750).The RT-qPCR results showed that the mRNA expression level of CMTM3 in NHA cells was 1.0±0.1, whereas in GBM cells U87, LN229, and U251, the levels were 2.1±0.3, 3.4±0.5, and 3.7±0.8, respectively, all significantly higher than that in NHA cells (all P<0.01). Western blot results demonstrated that the protein expression levels of CMTM3 in GBM cells U87, LN229, and U251 were 1.5±0.2, 1.8±0.2, and 1.9±0.1, respectively, also higher than that in NHA cells (0.7±0.2, all P<0.01), with the highest level observed in U251 cells. The CCK-8 assay, Flow cytometry, and Transwell migration experiments indicated that cell viability was inhibited in the sh-CMTM3 group, with an increase in the proportion of cells in the G 0/G 1 phase ( P<0.01) and a decrease in the S phase ( P<0.01), and the number of migrated cells was 233.6±35.5, lower than that in the sh-NC group ( P<0.001). Conversely, the OE-CMTM3 group showed enhanced cell viability, a reduction in the proportion of cells in the G 0/G 1 phase ( P<0.01), and an increase in the S phase ( P<0.01), and the number of migrated cells was 1212.0±20.8, higher than that in the OE-NC group ( P<0.001). However, in the OE-CMTM3+PDTC group, cell viability, cell cycle distribution (G 1, S, and G 2 phases), and cell migration numbers showed no significant changes (all P>0.05). Western blot analysis and NF-κB activation-nuclear translocation assay results indicated that in the sh-CMTM3 group, the p-p65/p65 ratio was 0.51±0.04 and the p-IκBα/IκBα ratio was 0.39±0.03, both lower than those in the sh-NC group (both P<0.01). The cytoplasmic staining rate was (49.29±1.98)%, higher than that in the sh-NC group ( P<0.01). In the OE-CMTM3 group, the p-p65/p65 ratio was 2.27±0.10 and the p-IκBα/IκBα ratio was 2.14±0.15, both higher than those in the OE-NC group (both P<0.01). The cytoplasmic staining rate was (18.96±1.44)%, lower than that in the OE-NC group ( P<0.01). In the OE-CMTM3+PDTC group, there were no significant differences in the p-p65/p65 ratio, p-IκBα/IκBα ratio, and cytoplasmic staining rate compared with the OE-NC group (all P>0.05). The subcutaneous tumorigenesis assay in nude mice showed that the tumor volume in the sh-CMTM3 group was (408.9±96.2) mm3, smaller than that in the sh-NC group ( P=0.003). The tumor volume in the OE-CMTM3 group was (1 514.5±251.5) mm3, larger than that in the OE-NC group ( P=0.005). Conclusions:In GBM, CMTM3 is highly expressed and negatively correlated with both OS and DFS of patients. CMTM3 regulates the proliferation and migration abilities of U251 cells through the NF-κB signaling pathway.


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