1.Traditional Chinese Medicine Regulates Signaling Pathways Related to Precancerous Lesions of Gastric Cancer: A Review
Maofu ZHANG ; Xinyu LI ; Yanyun SHEN ; Yeyuan LIU ; Jialin ZHONG ; Lulu CHEN ; Haihong ZHAO ; Zhongyang SONG ; Zhiming ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):297-306
Precancerous lesions of gastric cancer (PLGC) are a group of pathological changes caused by abnormalities in the structure, morphology, and differentiation of gastric mucosal epithelial cells. Since the early symptoms are hidden and non-specific, PLGC is not easy to be diagnosed and it has often developed into intermediate or advanced gastric cancer once being diagnosed and missed the best time for treatment. Accordingly, the incidence of this disease is increasing year by year, which lifts a heavy burden on the patients. The pathogenesis of PLGC is complex, involving inflammatory microenvironment, bile reflux, glycolysis, autophagy, and apoptosis. Currently, PLGC is mainly treated with anti-inflammatory and endoscopic therapies, which are difficult to curb the development of PLGC. Therefore, seeking a safe and effective therapy is an important topic of modern research. Traditional Chinese medicine (TCM), characterized by treatment based on syndrome differentiation and a holistic view, exerts effects via multiple pathways, mechanisms, and targets. Recent studies have confirmed that TCM can regulate the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR), Wnt/β-catenin, Sonic Hedgehog, nuclear factor-κB (NF-κB), Janus kinase/signal transducer and activator of transcription (JAK/STAT), hypoxia-inducible factor-1α (HIF-1α), neurogenic locus notch homolog protein (Notch), nuclear factor E2-related factor 2 (Nrf2) and other signaling pathways. By targeting these pathways, TCM can inhibit aerobic glycolysis, reduce oxidative stress, repair the inflammatory microenvironment, regulate cellular autophagy, and promote vascular normalization, thereby delaying or reversing PLGC. However, few researchers have systematically summarized the TCM regulation of PLGC-associated pathways. By reviewing the relevant articles at home and abroad, this paper summarized the roles of the above signaling pathways in the development of PLGC and the research progress in the regulation of signaling pathways by TCM in the treatment of PLGC, with a view to providing a new theoretical basis for the clinical research on PLGC and the drug development for this disease.
2.Analysis on clinical features and prognostic factors in 68 adult hemophagocytic syndrome
Rongyao ZHANG ; Yanqun SHEN ; Yigang GUO ; Zhangzhi LI ; Lulu ZHANG
China Modern Doctor 2025;63(12):61-64
Objective To explore the clinical features and prognostic factors of adult hemophagocytic syndrome(HPS).Methods The clinical data of 68 newly diagnosed patients with HPS who were hospitalized from December 2018 to December 2023 were retrospectively analyzed,and clinical features,treatment and prognostic factors of patients were analyzed.Results The median age of 68 patients was 49(17-75)years old,the most common cause was infection,40 cases(58.82%),and the most common clinical manifestation was fever,63 cases(92.6%).Of the 68 patients,12(17.65%)patients died and the median survival time was 32 months.Cox univariate analysis showed that the prognosis of adult HPS was affected by SF,epstein-barr virus(EBV)infection,platelet count(<20× 109/L),age over 60 years old,activated partial thromboplastin over 60s and other factors(P<0.05).Multivariate Cox analysis showed that EBV infection and platelet count(<20×109/L)were independent prognostic factors of adult HPS(P<0.05).Conclusion The clinical manifestations of adult HPS are not typical,and the prognosis of adult HPS is affected by many factors.EBV infection and platelet count(<20× 109/L)are independent risk factors for death.
3.Characteristics of gastric hepatoid adenocarcinoma: a clinicopathological and molecular analysis
Jie WANG ; Lulu SHEN ; Xin ZHANG ; Hongxia LU ; Yi JIA ; Jing LIU ; Peng BU ; Likun ZAN
Chinese Journal of Pathology 2025;54(7):748-754
Objective:To investigate the clinical, pathological, and molecular biological characteristics of gastric hepatoid adenocarcinoma (HAS) in order to provide reference for clinical treatment.Methods:Thirty-two patients diagnosed with hepatoid adenocarcinoma after radical gastrectomy for gastric cancer at Shanxi Cancer Hospital were included from January 2019 to December 2021. Immunohistochemistry, in situ hybridization, and next-generation sequencing (NGS) methods were used to analyze immune markers and molecular characteristics in the pathological tissues from 32 patients with HAS. Cox regression analysis and Kaplan-Meier method were used to analyze the prognostic factors of overall survival and disease-free survival.Results:Among the 32 patients with HAS, 26 were male, 6 were female; aged 28-77 years, with an median age 62.0 (53.8, 67.2) years. Fifteen cases of HAS were located in the cardia, 10 cases in the antrum, and 7 cases in the body of the stomach. The maximum diameter of the mass was 3-10 cm, and mainly ulcerative in gross. The immunohistochemistry and in situ hybridization results showed that the positive rates of AFP, SALLA4, and Glypican-3 were 68.8% (22/32), 68.8% (22/32), 78.1% (25/32), respectively; Seven patients had microsatellite status of dMMR. Two cases of HER2 gene amplification and 2 cases of EB virus positivity. The NGS results showed that HAS was often accompanied by multiple gene mutations, with 23 cases having ≥ 2 gene mutations and 6 cases having ≥10 gene mutations. The TP53 gene had the highest mutation frequency; 4 cases had genetic structural variations; 28 cases had copy number variation. In addition, there were 7 cases of MSI-H and 9 cases of TMB-H. Follow-up results showed that 12 cases died, 9 cases developed metastasis, and the shortest survival time was 5 months.Conclusions:Gastric HAS is a type of tumor with high invasiveness and poor prognosis. The combined detection of AFP, SALLA4 and Glypican-3 can improve the diagnostic rate of tumors. dMMR/MSI-H and TMB-H patients in HAS are significantly higher than those in ordinary gastric cancer, and the high frequency mutation genes in HAS are often accompanied by multiple potential therapeutic targets. Immunotherapy combined with chemotherapy and targeted therapy are expected to become the treatment direction of HAS.
4.Effects of Bushen Tiaojing Formula (补肾调经方) on Blastocyst Cell Apoptosis and Endoplasmic Reticulum Stress in Repeated Controlled Ovarian Stimulation Model Mice
Wenyan XIONG ; Beibei SHI ; Lulu SHEN ; Huilan DU
Journal of Traditional Chinese Medicine 2025;66(15):1579-1587
ObjectiveTo explore the effects of Bushen Tiaojing Formula (补肾调经方) on the quality of early embryos in repeated controlled ovarian stimulation (COS) and its possible mechanism. MethodsA total of 150 ICR female mice were divided into a normal group, a model group, an inhibitor group, a low-dose and a high-dose Bushen Tiaojing Formula group. Mice in the normal group, inhibitor group and model group were gavaged with distilled water 0.25 ml a day, and mice in the low- and high-dose groups were given 25.6 and 51.2 g/(kg·d) of Bushen Tiaojing Formula, respectively. All groups were gavaged once a day for 13 days as a cycle. Mice in the normal group were injected intraperitoneally with 0.1 ml normal saline on the 11th day of gavage, while mice in the other four groups were used to establish COS models. The inhibitor group was injected with the endoplasmic reticulum stress inhibitor 4-phenylbutyric acid 0.2 ml one hour before modelling. All groups were injected by gavage and intraperitoneal injection for 3 consecutive cycles, with an interval of 4 days between cycles. Immediately after the third intraperitoneal injection, mice were grouped with male mice of the same strain in a ratio of 2∶1, and at 8AM of the second day, the mice were examined, and those with spermatozoa or spermatozoa in the vaginal smears were recorded as pregnant. The mice were executed in the afternoon of the 4th day of pregnancy, and the blastocysts were obtained under an inverted microscope. The morphology of the blastocysts was observed, and the total number of blastocysts and the number of high-quality blastocysts were recorded to calculate the rate of high-quality blastocysts; the apoptosis of blastocyst cells was detected by the Tunel method, and the apoptosis rate was calculated; the endoplasmic reticulum molecular chaperone protein glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), B-lymphoblastoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), cystathionin 3 (Caspase-3) and cystathionin 12 (Caspase-12) protein levels and their mRNA expression were detected by immunofluorescent assay and RT-qPCR assay, respectively. ResultsIn the normal group, blastocysts had regular morphology, good morphological development and low fragmentation rate; in the model group, blastocysts were poorly developed, cell morphology was irregular, fragmentation rate was high, and there was some stagnation; in the inhibitor group and high-dose, low-dose Bushen Tiaojing Formula groups, cell morphology could be seen to be better developed, with regular morphology and less fragmentation rate. Compared with the normal group, the rate of high-quality blastocysts in the model group reduced, the rate of apoptosis of blastocyst cells increased, the levels of GRP78, CHOP, Caspase-12, Caspase-3, Bax protein and its mRNA expression in blastocysts increased, while the level of Bcl-2 protein and its mRNA reduced (P<0.01). Compared with the model group, the rate of high-quality blastocysts increased, the rate of apoptosis of blastocysts decreased, the levels of GRP78, CHOP, Caspase-12, Caspase-3, Bax protein and their mRNA expression decreased, and the levels of Bcl-2 protein and its mRNA expression increased in the blastocysts in the inhibitor group and the high-dose and low-dose Bushen Tiaojing Formula groups (P<0.01). Compared with the inhibitor group, GRP78, CHOP, Caspase-12, Bax protein levels and their mRNA expressions increased in the high-dose Bushen Tiaojing Formula group, and Caspase-12, Caspase-3, Bax protein levels and their mRNA expressions increased in the low-dose formula group (P<0.05 or P<0.01). ConclusionBushen Tiaojing Formula can inhibit the apoptosis of blastocyst cells caused by repeated controlled ovarian stimulation by improving endoplasmic reticulum stress, which plays a role in improving the quality of early embryos.
5.Gallstones, cholecystectomy, and cancer risk: an observational and Mendelian randomization study.
Yuanyue ZHU ; Linhui SHEN ; Yanan HUO ; Qin WAN ; Yingfen QIN ; Ruying HU ; Lixin SHI ; Qing SU ; Xuefeng YU ; Li YAN ; Guijun QIN ; Xulei TANG ; Gang CHEN ; Yu XU ; Tiange WANG ; Zhiyun ZHAO ; Zhengnan GAO ; Guixia WANG ; Feixia SHEN ; Xuejiang GU ; Zuojie LUO ; Li CHEN ; Qiang LI ; Zhen YE ; Yinfei ZHANG ; Chao LIU ; Youmin WANG ; Shengli WU ; Tao YANG ; Huacong DENG ; Lulu CHEN ; Tianshu ZENG ; Jiajun ZHAO ; Yiming MU ; Weiqing WANG ; Guang NING ; Jieli LU ; Min XU ; Yufang BI ; Weiguo HU
Frontiers of Medicine 2025;19(1):79-89
This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans
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Mendelian Randomization Analysis
;
Gallstones/complications*
;
Female
;
Male
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Cholecystectomy/statistics & numerical data*
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Middle Aged
;
Risk Factors
;
Aged
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Adult
;
Neoplasms/etiology*
;
Stomach Neoplasms/epidemiology*
6.Spicy food consumption and risk of vascular disease: Evidence from a large-scale Chinese prospective cohort of 0.5 million people.
Dongfang YOU ; Dianjianyi SUN ; Ziyu ZHAO ; Mingyu SONG ; Lulu PAN ; Yaqian WU ; Yingdan TANG ; Mengyi LU ; Fang SHAO ; Sipeng SHEN ; Jianling BAI ; Honggang YI ; Ruyang ZHANG ; Yongyue WEI ; Hongxia MA ; Hongyang XU ; Canqing YU ; Jun LV ; Pei PEI ; Ling YANG ; Yiping CHEN ; Zhengming CHEN ; Hongbing SHEN ; Feng CHEN ; Yang ZHAO ; Liming LI
Chinese Medical Journal 2025;138(14):1696-1704
BACKGROUND:
Spicy food consumption has been reported to be inversely associated with mortality from multiple diseases. However, the effect of spicy food intake on the incidence of vascular diseases in the Chinese population remains unclear. This study was conducted to explore this association.
METHODS:
This study was performed using the large-scale China Kadoorie Biobank (CKB) prospective cohort of 486,335 participants. The primary outcomes were vascular disease, ischemic heart disease (IHD), major coronary events (MCEs), cerebrovascular disease, stroke, and non-stroke cerebrovascular disease. A Cox proportional hazards regression model was used to assess the association between spicy food consumption and incident vascular diseases. Subgroup analysis was also performed to evaluate the heterogeneity of the association between spicy food consumption and the risk of vascular disease stratified by several basic characteristics. In addition, the joint effects of spicy food consumption and the healthy lifestyle score on the risk of vascular disease were also evaluated, and sensitivity analyses were performed to assess the reliability of the association results.
RESULTS:
During a median follow-up time of 12.1 years, a total of 136,125 patients with vascular disease, 46,689 patients with IHD, 10,097 patients with MCEs, 80,114 patients with cerebrovascular disease, 56,726 patients with stroke, and 40,098 patients with non-stroke cerebrovascular disease were identified. Participants who consumed spicy food 1-2 days/week (hazard ratio [HR] = 0.95, 95% confidence interval [95% CI] = [0.93, 0.97], P <0.001), 3-5 days/week (HR = 0.96, 95% CI = [0.94, 0.99], P = 0.003), and 6-7 days/week (HR = 0.97, 95% CI = [0.95, 0.99], P = 0.002) had a significantly lower risk of vascular disease than those who consumed spicy food less than once a week ( Ptrend <0.001), especially in those who were younger and living in rural areas. Notably, the disease-based subgroup analysis indicated that the inverse associations remained in IHD ( Ptrend = 0.011) and MCEs ( Ptrend = 0.002) risk. Intriguingly, there was an interaction effect between spicy food consumption and the healthy lifestyle score on the risk of IHD ( Pinteraction = 0.037).
CONCLUSIONS
Our findings support an inverse association between spicy food consumption and vascular disease in the Chinese population, which may provide additional dietary guidance for the prevention of vascular diseases.
Humans
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Male
;
Female
;
Prospective Studies
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Middle Aged
;
Aged
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Vascular Diseases/etiology*
;
Risk Factors
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China/epidemiology*
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Adult
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Proportional Hazards Models
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Cerebrovascular Disorders/epidemiology*
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East Asian People
7.Probe-based label-free SERS for identification of breast cancer-induced serum metabolic profiles in patients
Meng WANG ; Xuejing SHEN ; Jia LIU ; Lulu SHANG ; Mo ZHANG
Basic & Clinical Medicine 2025;45(5):651-657
Objective To detect Serum metabolites with label-free surface-enhanced Raman spectroscopy(SERS)for quickly distinguishing the metabolic profiles of breast cancer patients and healthy subjects.Methods A kind of Plasma nano-material was synthesized as a probe for SERS,which has also been used to detect Raman reporter mol-ecules to assess its detection capability.Serum samples from breast cancer patients and healthy subjects were col-lected and the proteins were precipitated with methanol and removed to collect serum metabolites.Probe-based SERS was used to analyze the serum metabolites of patients and explore the changes in the metabolic profiles of breast cancer patients.Results The SERS probe was synthesized and validated.An analytical method based on SERS probe was established,which achieved a linear range(LR)of 4 orders of magnitude and a limit of detection(LOD)up to 10 nmol/L.Raman spectra of serum metabolites from 5 breast cancer patients and 5 healthy subjects were analyzed to study differences in metabolite changes.Conclusions In this study,the molecular spectrum differences of serum metabolites in breast cancer patients were screened by probe-based SERS method,which pro-vides a technology support research on the metabolic changes caused by breast cancer so potentially provide a new method for fast breast cancer screening.
8.Spectral CT material separation technology for diagnosing traumatic bone marrow edema in limbs
Chen WANG ; Lulu YOU ; Jian DU ; Xiangyu WANG ; Wei LIU ; Lan WANG ; Long SHEN
Chinese Journal of Medical Imaging Technology 2025;41(4):642-645
Objective To observe the value of spectral CT material separation technology for diagnosing traumatic bone marrow edema in limbs.Methods Totally 51 patients with limb traumatic bone marrow edema were retrospectively enrolled and divided into young group(n=26,18-43 years)and middle-aged group(n=25,46-74 years).Taken MRI as reference standard,the efficacy of spectral CT Water-hydroxyapatite(HAP)image for diagnosing bone marrow edema in trauma area was analyzed,and the Water-HAP density values were compared between groups.Results No significant difference of diagnosing bone marrow edema was found between spectral CT and MRI(x2=0.201,P=0.654),and the consistency was high(Kappa=0.774).Water-HAP density value in bone marrow edema area was higher than that in non bone marrow edema area(t=24.634,P<0.05),and no significant difference of Water-HAP density values in bone marrow edema area nor non bone marrow edema area was found between young group and middle-aged group(both P>0.05).Conclusion Spectral CT material separation technology was helpful for diagnosing traumatic bone marrow edema in limbs.
9.Global Epidemic Status of Colorectal Cancer and Rela-tionship of Colorectal Cancer Burden with the Human De-velopment Index
Lulu DING ; Yuanyou XU ; Yongsheng CHEN ; Rong SHEN ; Jian ZHU
China Cancer 2025;34(8):611-617
[Purpose]To analyze global epidemic status of colorectal cancer and explore the rela-tionship between the human development index(HDI)and the burden of colorectal cancer.[Methods]Based on the GLOBOCAN 2022 estimation data,the disease burden of colorectal can-cer in different regions,countries,and levels of HDI were analyzed.Spearman's rank test was used to explore the correlation between HDI and colorectal cancer disease burden.[Results]The estimated global incidence of colorectal cancer in 2022 was 1 926 425 cases(1 069 446 for male and 856 979 for female),with a age-standardized incidence rate of 18.4/105(21.9/105 for male and 15.2/105 for female),and cumulative risk of incidence of 2.10%(2.60%for male and 1.70%for female);the estimated number of deaths was 904 019(499 775 for male and 404 244 for fe-male),with a age-standardized mortality rate of 8.1/105(9.9/105 for male and 6.5/105 for female)and cumulative risk of death of 0.84%(1.00%for male and 0.65%for female).1-crude mortality rate/crude incidence rate(1-M/I)was 0.53(0.53 for male and 0.53 for female).Large disparities were in the disease burden of colorectal cancer between different regions and countries.After grouped by HDI,we found that the age-standardized incidence rates in very high,high,median,and low HDI regions were 28.6/105,18.1/105,6.7/105,and 6.4/105,and the standardized mortality rates were 10.5/105,8.3/105,3.9/105,and 4.5/105,with 1-M/I of 0.57,0.52,0.43 and 0.30,respec-tively;and the incidence and mortality rates were increasing with age.Spearman's correlation analysis showed a strong positive correlation between HDI and colorectal cancer in age-standardized incidence(r=0.84),age-standardized mortality(r=0.71)and 1-M/I(r=0.82)(all P<0.001).[Con-clusion]The global burden of colorectal cancer remains high.There are disparities in the disease burden among countries and regions,which is positively correlated with their HDI levels,indicating that the colorectal cancer prevention and treatment strategies should be developed based on the conditions of each regions and countries accordingly.
10.Analysis on clinical features and prognostic factors in 68 adult hemophagocytic syndrome
Rongyao ZHANG ; Yanqun SHEN ; Yigang GUO ; Zhangzhi LI ; Lulu ZHANG
China Modern Doctor 2025;63(12):61-64
Objective To explore the clinical features and prognostic factors of adult hemophagocytic syndrome(HPS).Methods The clinical data of 68 newly diagnosed patients with HPS who were hospitalized from December 2018 to December 2023 were retrospectively analyzed,and clinical features,treatment and prognostic factors of patients were analyzed.Results The median age of 68 patients was 49(17-75)years old,the most common cause was infection,40 cases(58.82%),and the most common clinical manifestation was fever,63 cases(92.6%).Of the 68 patients,12(17.65%)patients died and the median survival time was 32 months.Cox univariate analysis showed that the prognosis of adult HPS was affected by SF,epstein-barr virus(EBV)infection,platelet count(<20× 109/L),age over 60 years old,activated partial thromboplastin over 60s and other factors(P<0.05).Multivariate Cox analysis showed that EBV infection and platelet count(<20×109/L)were independent prognostic factors of adult HPS(P<0.05).Conclusion The clinical manifestations of adult HPS are not typical,and the prognosis of adult HPS is affected by many factors.EBV infection and platelet count(<20× 109/L)are independent risk factors for death.

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