1.Oxylipidomics Combined with Transcriptomics Reveals Mechanism of Jianpi Huogu Prescription in Treating Steroid-induced Osteonecrosis of Femoral Head in Rats
Lili WANG ; Qun LI ; Zhixing HU ; Qianqian YAN ; Liting XU ; Xiaoxiao WANG ; Chunyan ZHU ; Yanqiong ZHANG ; Weiheng CHEN ; Haijun HE ; Chunfang LIU ; Na LIN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):190-199
ObjectiveTo unveil the mechanism of Jianpi Huogu prescription (JPHGP) in ameliorating the dyslipidemia of steroid-induced osteonecrosis of the femur head (SONFH) by oxylipidomics combined with transcriptomics. MethodsSixty SD rats were assigned into normal, model, low-, medium-, and high-dose (2.5, 5, 10 g·kg-1, respectively) JPHGP, and Jiangushengwan (1.53 g·kg-1) groups. Lipopolysaccharide was injected into the tail vein at a dose of 20 μg·kg-1 on days 1 and 2, and methylprednisolone sodium succinate was injected at a dose of 40 mg·kg-1 into the buttock muscle on days 3 to 5. The normal group received an equal volume of normal saline. Drug administration by gavage began 4 weeks after the last injection, and samples were taken after administration for 8 weeks. Hematoxylin-eosin staining was conducted to reveal the histopathological changes of the femoral head, and the number of adipocytes, the rate of empty bone lacunae, and the trabecular area were calculated. Micro-computed tomography was used for revealing the histological and histomorphometrical changes of the femoral head. Enzyme-linked immunosorbent assay was employed to measure the serum levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), apolipoprotein A1 (ApoA1), and apolipoprotein B (ApoB). At the same time, the femoral head was collected for oxylipidomic and transcriptomic detection. The differential metabolites and differential genes were enriched and analyzed, and the target genes regulating lipid metabolism were predicted. The predicted target proteins were further verified by molecular docking, immunohistochemistry, and Western blot. ResultsCompared with the normal group, the model group showcased thinning of the femoral head, trabecular fracture, karyopyknosis, subchondral cystic degeneration, increases in the number of adipocytes and the rate of empty bone lacunae (P<0.01), a reduction in the trabecular area (P<0.01), decreases in BMD, Tb.Th, Tb.N, and BV/TV, and increases in Tb.Sp and BS/BV (P<0.01). Compared with the model group, the JPHGP groups showed no obvious thinning of the femoral head or subchondroidal cystic degeneration. The high- and medium-dose JPHGP groups presented declines in the number of adipocytes and the rate of empty bone lacunae, an increase in the trabecular area (P<0.05, P<0.01), rises in BMD, Tb.Th, Tb.N, and BV/TV, and decreases in Tb.Sp and BS/BV (P<0.05, P<0.01). Compared with the normal group, the model group showcased raised serum levels of TG, TC, LDL, and ApoB and lowered serum levels of HDL and ApoA1 (P<0.01). Compared with the model group, the JPHGP groups had lowered serum levels of TG, TC, LDL, and ApoB (P<0.05, P<0.01) and a risen serum level of ApoA1 (P<0.05, P<0.01). Moreover, the serum level of HDL in the high-dose JPHGP group increased (P<0.01). A total of 19 different metabolites of disease set and drug set were screened out by oxylipidomics of the femoral head, and 119 core genes with restored expression were detected by transcriptomics. The enriched pathways were mainly concentrated in inflammation, lipids, apoptosis, and osteoclast differentiation. Molecular docking, immunohistochemistry, and Western blot results showed that compared with the normal group, the model group displayed increased content of 5-lipoxygenase (5-LO) and peroxisome proliferator-activated receptor γ (PPARγ) in the femoral head (P<0.01). Compared with the model group, medium- and high-dose JPHGP reduced the content of 5-LO and PPARγ (P<0.05, P<0.01). ConclusionJPHGP can restore the levels of oxidized lipid metabolites by regulating the 5-LO-PPARγ axis to treat SONFH in rats. Relevant studies provide experimental evidence for the efficacy mechanism of JPHGP in the treatment of SONFH.
2.Oxylipidomics Combined with Transcriptomics Reveals Mechanism of Jianpi Huogu Prescription in Treating Steroid-induced Osteonecrosis of Femoral Head in Rats
Lili WANG ; Qun LI ; Zhixing HU ; Qianqian YAN ; Liting XU ; Xiaoxiao WANG ; Chunyan ZHU ; Yanqiong ZHANG ; Weiheng CHEN ; Haijun HE ; Chunfang LIU ; Na LIN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):190-199
ObjectiveTo unveil the mechanism of Jianpi Huogu prescription (JPHGP) in ameliorating the dyslipidemia of steroid-induced osteonecrosis of the femur head (SONFH) by oxylipidomics combined with transcriptomics. MethodsSixty SD rats were assigned into normal, model, low-, medium-, and high-dose (2.5, 5, 10 g·kg-1, respectively) JPHGP, and Jiangushengwan (1.53 g·kg-1) groups. Lipopolysaccharide was injected into the tail vein at a dose of 20 μg·kg-1 on days 1 and 2, and methylprednisolone sodium succinate was injected at a dose of 40 mg·kg-1 into the buttock muscle on days 3 to 5. The normal group received an equal volume of normal saline. Drug administration by gavage began 4 weeks after the last injection, and samples were taken after administration for 8 weeks. Hematoxylin-eosin staining was conducted to reveal the histopathological changes of the femoral head, and the number of adipocytes, the rate of empty bone lacunae, and the trabecular area were calculated. Micro-computed tomography was used for revealing the histological and histomorphometrical changes of the femoral head. Enzyme-linked immunosorbent assay was employed to measure the serum levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), apolipoprotein A1 (ApoA1), and apolipoprotein B (ApoB). At the same time, the femoral head was collected for oxylipidomic and transcriptomic detection. The differential metabolites and differential genes were enriched and analyzed, and the target genes regulating lipid metabolism were predicted. The predicted target proteins were further verified by molecular docking, immunohistochemistry, and Western blot. ResultsCompared with the normal group, the model group showcased thinning of the femoral head, trabecular fracture, karyopyknosis, subchondral cystic degeneration, increases in the number of adipocytes and the rate of empty bone lacunae (P<0.01), a reduction in the trabecular area (P<0.01), decreases in BMD, Tb.Th, Tb.N, and BV/TV, and increases in Tb.Sp and BS/BV (P<0.01). Compared with the model group, the JPHGP groups showed no obvious thinning of the femoral head or subchondroidal cystic degeneration. The high- and medium-dose JPHGP groups presented declines in the number of adipocytes and the rate of empty bone lacunae, an increase in the trabecular area (P<0.05, P<0.01), rises in BMD, Tb.Th, Tb.N, and BV/TV, and decreases in Tb.Sp and BS/BV (P<0.05, P<0.01). Compared with the normal group, the model group showcased raised serum levels of TG, TC, LDL, and ApoB and lowered serum levels of HDL and ApoA1 (P<0.01). Compared with the model group, the JPHGP groups had lowered serum levels of TG, TC, LDL, and ApoB (P<0.05, P<0.01) and a risen serum level of ApoA1 (P<0.05, P<0.01). Moreover, the serum level of HDL in the high-dose JPHGP group increased (P<0.01). A total of 19 different metabolites of disease set and drug set were screened out by oxylipidomics of the femoral head, and 119 core genes with restored expression were detected by transcriptomics. The enriched pathways were mainly concentrated in inflammation, lipids, apoptosis, and osteoclast differentiation. Molecular docking, immunohistochemistry, and Western blot results showed that compared with the normal group, the model group displayed increased content of 5-lipoxygenase (5-LO) and peroxisome proliferator-activated receptor γ (PPARγ) in the femoral head (P<0.01). Compared with the model group, medium- and high-dose JPHGP reduced the content of 5-LO and PPARγ (P<0.05, P<0.01). ConclusionJPHGP can restore the levels of oxidized lipid metabolites by regulating the 5-LO-PPARγ axis to treat SONFH in rats. Relevant studies provide experimental evidence for the efficacy mechanism of JPHGP in the treatment of SONFH.
3.Multidisciplinary expert consensus on weight management for overweight and obese children and adolescents based on healthy lifestyle
HONG Ping, MA Yuguo, TAO Fangbiao, XU Yajun, ZHANG Qian, HU Liang, WEI Gaoxia, YANG Yuexin, QIAN Junwei, HOU Xiao, ZHANG Yimin, SUN Tingting, XI Bo, DONG Xiaosheng, MA Jun, SONG Yi, WANG Haijun, HE Gang, CHEN Runsen, LIU Jingmin, HUANG Zhijian, HU Guopeng, QIAN Jinghua, BAO Ke, LI Xuemei, ZHU Dan, FENG Junpeng, SHA Mo, Chinese Association for Student Nutrition & ; Health Promotion, Key Laboratory of Sports and Physical Fitness of the Ministry of Education,〖JZ〗 Engineering Research Center of Ministry of Education for Key Core Technical Integration System and Equipment,〖JZ〗 Key Laboratory of Exercise Rehabilitation Science of the Ministry of Education
Chinese Journal of School Health 2025;46(12):1673-1680
Abstract
In recent years, the prevalence of overweight and obesity among children and adolescents has risen rapidly, posing a serious threat to their physical and mental health. To provide scientific, systematic, and standardized weight management guidance for overweight and obese children and adolescents, the study focuses on the core concept of healthy lifestyle intervention, integrates multidisciplinary expert opinions and research findings,and proposes a comprehensive multidisciplinary intervention framework covering scientific exercise intervention, precise nutrition and diet, optimized sleep management, and standardized psychological support. It calls for the establishment of a multi agent collaborative management mechanism led by the government, implemented by families, fostered by schools, initiated by individuals, optimized by communities, reinforced by healthcare, and coordinated by multiple stakeholders. Emphasizing a child and adolescent centered approach, the consensus advocates for comprehensive, multi level, and personalized guidance strategies to promote the internalization and maintenance of a healthy lifestyle. It serves as a reference and provides recommendations for the effective prevention and control of overweight and obesity, and enhancing the health level of children and adolescents.
4.Acute lymphoblastic leukemia secondary to Burkitt lymphoma in children: report of 1 case and review of literature
Chaorong WANG ; Haijun WANG ; Lechen LI ; Nuoyan SHI ; Luyue DING ; Linlin LIU ; Tianyou WANG ; Wei LIU ; Yanna MAO ; Wei LIN
Journal of Leukemia & Lymphoma 2025;34(8):489-493
Objective:To improve the understanding of acute lymphoblastic leukemia (ALL) secondary to Burkitt lymphoma (BL) in children.Methods:The clinical data of a child with ALL secondary to BL who was admitted to Children's Hospital Affiliated to Zhengzhou University in June 2024 were retrospectively analyzed, and the relevant literature was reviewed.Results:The patient was a boy with the age of 8 years and 8 months. He presented with a neck mass at the age of 4 years and 6 months, and pathological examination revealed a diagnosis of BL with clinical stage Ⅲ. The patient was given regular chemotherapy according to the Chinese Children's Lymphoma Group non-Hodgkin lymphoma mature B-cell 2017 protocol-B2 regimen. PET-CT showed recurrence of lymphoma in 6 months after the suspension of treatment. The patient was given with placement of 125I particles, oral etoposide and dexamethasone, and traditional Chinese medicine. The patient was admitted to hospital at the age of 8 years and 8 months with fever and skin hemorrhagic spots, bone marrow morphology, immunology, cytogenetics and molecular biology typing indicated a diagnosis of B-ALL with TCF3::PBX1 fusion gene. The patient received induction chemotherapy according to the Chinese Children's Leukemia Group-ALL 2018 protocol. A review of bone marrow cytology achieved complete remission on the 33rd day of chemotherapy, and minimal residual disease detected by flow cytometry indicated less than 0.01%. TCF3::PBX1 fusion gene was negative. Conclusions:ALL secondary to BL in children is rare, and the ALL treatment regimens are effective.
5.Study on Mechanism of Hot Compress with Sangzhi Shengjiang Decoction in Relieving Pain and Improving Hemorheology of Patients with Femoral Head Necrosis
Xin ZHANG ; Meng ZHANG ; Jian LIU ; Haijun HE
Journal of Guangzhou University of Traditional Chinese Medicine 2025;42(2):315-321
Objective To explore the therapeutic mechanism of hot compress with Sangzhi Shengjiang Decoction(manily composed of Zingiberis Rhizoma Recens,Mori Ramulus,Cinnamomi Ramulus,Speranskiae Tuberculatae Herba,and Cervi Cornus Colla)in relieving pain and improving hemorheology of patients with femoral head necrosis(FHN).Methods A total of 104 patients with FHN who admitted to Guang'anmen Hospital Baoding,China Academy of Chinese Medical Sciences from May 2022 to May 2024 were randomly divided into the control group and the treatment group according to the random number table method,with 52 cases in each group.The control group was treated with Alendronate Sodium orally,and the treatment group was given hot compress with Sangzhi Shengjiang Decoction on the basis of treatment for the control group.The course of treatment for the two groups covered three months.Before and after the treatment,the traditional Chinese medicine(TCM)syndrome score,Harris score of joint function,Visual Analogue Scale(VAS)score for pain,and the levels of hemorheology indicators,bone metabolism indicators,and bone mineral density(BMD)of proximal femur and lumbar trabecular bone in the two groups were observed.After treatment,the clinical efficacy of patients in the two groups was evaluated.Results(1)After three months of treatment,the total effective rate of the treatment group was 92.31%(48/52)and that of the control group was 71.15%(37/52),and the intergroup comparison(tested by chi-square test)showed that the clinical efficacy of the treatment group was significantly superior to that of the control group(P<0.01).(2)After treatment,the scores of TCM symptoms such as soreness and weakness in the waist and knee,claudication,restlessness and insomnia,and soreness and heaviness of lower limbs in the two groups were decreased compared with those before treatment(P<0.05),and the decreases in the treatment group were significantly superior to that in the control group(P<0.01).(3)After treatment,the Harris scores of joint function in the two groups were increased(P<0.05)and the VAS scores for pain were decreased compared with those before treatment(P<0.05),and the increase of Harris scores and the decrease of VAS scores in the treatment group were significantly superior to those in the control group(P<0.01).(4)After treatment,the levels of hemorheology indicators such as erythrocyte sedimentation rate(ESR),whole blood low-shear viscosity(LBV),and whole blood high-shear viscosity(HBV)in the two groups were improved compared with those before treatment(P<0.05),and the improvement in the treatment group was significantly superior to that in the control group(P<0.01).(5)After treatment,the levels of bone metabolism indicators such as serum N-terminal mid-fragment of osteocalcin(N-MID)β-C-terminal telopeptide of type Ⅰ collagen(β-CTX)and total procollagen type Ⅰ N-terminal propeptide(T-PINP)levels of patients in the two groups were decreased compared with those before treatment(P<0.05),and serum 25-hydroxy vitamin D[25-(OH)D]level was increased compared with that before treatment(P<0.05).The decrease of serum N-MID,β-CTX and T-PINP levels and the increase of serum 25-(OH)D level in the treatment group were significantly superior to those in the control group(P<0.01).(6)After treatment,BMD of proximal femur and lumbar trabecular bone in the two groups was increased compared with that before treatment(P<0.05),and the increase in the treatment group was significantly superior to that in the control group(P<0.01).Conclusion Hot compress with Sangzhi Shengjiang Decoction exerts certain efficacy for the treatment of patients with FHN.The therapy is effective on reducing the scores of TCM syndrome,relieving pain,improving joint function,regulating bone metabolism and bone density,improving hemorheology indicators,and presenting remarkable therapeutic effect.
6.Therapeutic Mechanism of Taohong Siwu Decoction in Recovering Joint Muscle Strength and Bone Mineral Density of Patients After Hip Preservation Surgery for Osteonecrosis of the Femoral Head
Xin ZHANG ; Meng ZHANG ; Jian LIU ; Haijun HE
Journal of Guangzhou University of Traditional Chinese Medicine 2025;42(8):1890-1897
Objective To explore the mechanism of Taohong Siwu Decoction in recovering joint muscle strength and bone mineral density(BMD)in patients after hip preservation surgery for osteonecrosis of the femoral head(ONFH).Methods A total of 110 ONFH patients admitted to Guang'anmen Hospital Baoding Branch,China Academy of Chinese Medical Sciences from April 2022 to April 2024 were enrolled.The patients were equally randomized into a control group and a study group using a random number table,with 55 cases in each group.All patients underwent core decompression surgery and then were given postoperative conventional western medical treatment,and the study group received additional modified Taohong Siwu Decoction.The course of treatment lasted for 8 weeks.Before and after treatment,the two groups were observed in the changes of traditional Chinese medicine(TCM)syndrome scores,Visual Analogue Scale(VAS)score for pain,Harris hip score,joint muscle strength,bone mineral density(BMD),hemorheological parameters(including plasma viscosity,whole blood high-shear viscosity,and whole blood low-shear viscosity),and bone metabolism markers[including alkaline phosphatase(ALP),osteocalcin(BGP),and bone morphogenetic protein 2(BMP-2)].After treatment,the clinical efficacy was evaluated between groups.Results(1)After 8 weeks of treatment,the total effective rate in the study group was 92.73%(51/55),which was significantly higher than that in the control group(72.73%,40/55).The intergroup comparison showed a statistically significant difference(χ2=7.698,P<0.01).(2)After treatment,scores for hip pain,soreness and weakness of the lower back and knees,mental fatigue,and deep-thin-choppy pulse decreased in both groups compared with those before treatment(P<0.05).Moreover,the magnitude of reduction in all these scores was significantly greater in the study group than that in the control group(P<0.01).(3)After treatment,the VAS scores for pain severity decreased in both groups compared with baseline(P<0.05),while the Harris scores for joint function increased in both groups(P<0.05).Furthermore,the magnitude of reduction in VAS scores and the magnitude of improvement in Harris scores were both significantly greater in the study group than those in the control group(P<0.01).(4)After treatment,plasma viscosity,high-shear whole blood viscosity,and low-shear whole blood viscosity decreased in both groups compared with those before treatment(P<0.05).Additionally,the reductions in all these parameters were significantly more pronounced in the study group than in the control group(P<0.01).(5)After treatment,serum alkaline phosphatase(ALP)levels decreased in both groups(P<0.05),while serum osteocalcin(BGP)and bone morphogenetic protein-2(BMP-2)levels increased in both groups(P<0.05).Crucially,the magnitude of reduction in serum ALP levels and the magnitude of elevation in serum BGP and BMP-2 levels were all significantly greater in the study group than those in the control group(P<0.01).(6)After treatment,in the study group,the number of patients with Grade 3 muscle strength significantly decreased while the number with Grade 4 muscle strength significantly increased compared with those before treatment(P<0.05).In contrast,although the control group showed some improvement in joint muscle strength,the changes were not statistically significant(P>0.05).After treatment,the intergroup comparisons showed that the study group had a significantly smaller number of patients with Grade 3 muscle strength and a significantly larger number with Grade 4 muscle strength than the control group(P<0.01).(7)After treatment,both local femoral head BMD and average BMD increased in both groups compared with those before treatment(P<0.05).The magnitude of increase in both local and average BMD was significantly greater in the study group than that in the control group(P<0.01).Conclusion The application of Taohong Siwu Decoction in the treatment of in patients after hip preservation surgery for ONFH is effective on reducing TCM syndrome scores,alleviating pain,improving joint function and hemorheology,and restoring BMD and bone metabolism indicators,which enhances the overall clinical efficacy for the patients.
7.Effect of practicing Traditional Chinese Medicine guidance on health status in weightless conditions
Xiaorui WU ; Haijun HAN ; Junlian LIU ; Quanchun FAN ; Liguo GUO ; Yu LIU ; Jiaping WANG ; Jihong SHEN ; Xining CHEN
Space Medicine & Medical Engineering 2025;36(4):385-388
Objective To study the effect of practicing traditional Chinese medicine(TCM)guidance on the health in weightless conditions based on the examination results of the TCM diagnostic instrument.Methods 6 subjects in weightless conditions practiced TCM guidance for 14 consecutive days,once a day for 8 minutes each time.The Digital TCM Diagnostic Instrument and TCM Syndrome Diagnosis Scale were used to collect information before and after their practice of TCM guidance through diagnostic methods of observation,palpation and inquiry according to TCM theory.The data such as the degree of virtual-reality,pulse rate,and characteristic parameters of pulse diagrams h3/h1,h4/h1,t1,h1/t1 were processed and analyzed,and the changes before and after the practice were compared.Results Compared with before the practice,the degree of deficiency syndrome was significantly reduced after practicing TCM guidance(P<0.05),the pulse rate was significantly decreased(P<0.01),and the pulse diagnosis parameters h3/h1 and t1 were significantly decreased(P<0.05),while h4/h1 and h1/t1 showed no significant changes.Conclusion Practicing TCM guidance in weightless conditions is helpful for enhance cardiovascular regulatory function,correcting symptom bias,adjusting the body's balance state,and has a positive effect on health.
8.Porphyromonas gingivalis promotes the occurrence of esophageal squamous cell carcinoma via an inflammatory microenvironment
Haijun XU ; Yijun QI ; Dangrou WU ; Qiwei LIU ; Pan CHEN ; Mengxiang LI ; Yelin JIAO ; Haojie RUAN ; Zhitao LI ; Shegan GAO
Chinese Journal of Oncology 2024;46(8):746-754
Objective:To investigate the role of an inflammatory microenvironment induced by Porphyromonasgingivalis ( P. gingivalis) in the occurrence of esophageal squamous cell carcinoma (ESCC) in mice. Methods:A total of 180 C57BL/6 mice were randomly divided into 6 groups, i.e. control group, P. gingivalis group, 4NQO group, 4NQO + P. gingivalis group, 4NQO + P. gingivalis + celecoxib group, and 4NQO + P. gingivalis + antibiotic cocktail (ABC, including metronidazole, neomycin, ampicillin, and vancomycin) group, with 30 mice in each group, using the random number table. All mice were normalized by treatment with ABC in drinking water for 2 weeks. In the following 2 weeks, the mice in the control group and the P. gingivalis group were given drinking water, while the other 4 groups were treated with 30 μg/ml 4NQO in the drinking water. In weeks 11-12, the mice in the P. gingivalis group, the 4NQO + P. gingivalis group, the 4NQO + P. gingivalis + celecoxib group, and the 4NQO + P. gingivalis + ABC group were subjected to ligation of the second molar in oral cavity followed by oral P. gingivalis infection thrice weekly for 24 weeks in weeks 11-34. In weeks 13-34, the mice in 4NQO + P. gingivalis+celecoxib group and 4NQO + P. gingivalis + ABC group were administered with celecoxib and ABC for 22 weeks, respectively. At the end of 34 weeks, gross and microscopic alterations were examined followed by RT-qPCR and immunohistochemistry to examine the expression profiles of inflammatory- and tumor-molecules in esophagi of mice. Results:At 34 weeks, 4NQO treatment alone did not affect the foci of papillary hyperproliferation, diseased area, and the thickness of the esophageal wall, but significantly enhanced the foci of hyperproliferation (median 1.00, P<0.05) and mild/moderate dysplasia (median 2.00, P<0.01). In addition, the expression levels of IL-6 [8.35(3.45,8.99)], IL-1β [6.90(2.01,9.72)], TNF-α [12.04(3.31,14.08)], c-myc [2.21(1.80,3.04)], pSTAT3, Ki-67, and pH2AX were higher than those in the control group. The pathological changes of the esophageal mucosa were significantly more overt in the 4NQO + P. gingivalis group in terms of the foci of papillary hyperproliferation (median 2.00), diseased area (median 2.51 mm 2), the thickness of the esophageal wall (median 172.52 μm), the foci of hyperproliferation (median 1.00, P<0.05), and mild/moderate dysplasia (median 1.00, P<0.01). In mice of the 4NQO + P. gingivalis group, the expression levels of IL-6 [12.27(5.35,22.08)], IL-1β [13.89(10.04,15.96)], TNF-α [19.56(6.07,20.36)], IFN-γ [11.37(8.23,20.07)], c-myc [2.62(1.51,4.25)], cyclin D1 [4.52(2.68,7.83)], nuclear pSTAT3, COX-2, Ki-67, and pH2AX were significantly increased compared with the mice in the control group. In mice of the 4NQO + P. gingivalis group, the diseased area, invasive malignant foci as well as pSTAT3 and pH2AX expression were significantly blunted by celecoxib. Treatment with ABC markedly reduced the papillary hyperproliferative foci, invasive malignant foci, and pSTAT3 expression but not pH2AX. Conclusions:P. gingivalis promotes the occurrence of esophageal squamous cell carcinoma in mice by inducing an inflammatory microenvironment primed with 4NQO induced DNA damage. Clearance of P. gingivalis with ABC or anti-inflammatory intervention holds promise for prevention of esophageal squamous cell malignant pathogenesis via blockage of IL-6/STAT3 signaling and amelioration of inflammation.
9.Study on the application value of fecal SDC2 gene methylation detection in colorectal cancer screening of urban residents in Zengcheng District in Guangzhou City
Yan HE ; Fangfang XU ; Haijun ZUO ; Wei CHEN ; Zhibin LIU ; Zebang LIU ; Xuezhen CHEN ; Qingshen HUI ; Gengwen ZOU ; Zhenbin CAI ; Yang LIU ; Haoshun TAN ; Hongfeng ZHOU ; Jianping WANG
Chinese Journal of Preventive Medicine 2024;58(7):1020-1028
Objective:To investigate the application value of fecal Syndecan-2 (SDC2) gene methylated SDC2 (m SDC2) detection in colorectal cancer (CRC) screening among urban residents in Guangzhou City. Methods:A cross-sectional study was conducted in Shitan Town, Zengcheng District, Guangzhou City from July to December 2022. A community-based screening program for CRC was conducted among residents aged 40-74 years old. m SDC2 detection was employed in the participants, and those with positive results should be recommended to receive colonoscopy examination. The positive rate of m SDC2 detection, colonoscopy compliance rate, detection rate of intestinal lesions and clinicopathological characteristics were observed. The relationship between cycle threshold (CT) value of m SDC2 and intestinal lesions was explored. Further, the cost-effectiveness of screening was evaluated. Results:A total of 8 189 fecal samples were collected from 8 877 participants with the recovery rate of 92.25%. 8 048 qualified samples were enrolled in this study, consisted of 3 182 males (39.54%) and 4 866 females (60.46%), with the average age of 56 years old (40-74 years). The positive rate of m SDC2 detection was 7.99% (643/8 048), and the compliance rate of colonoscopy was 73.10% (470/643). 20 cases (4.25%) of colorectal cancer, 109 cases (23.19%) of advanced adenoma, 145 cases (30.85%) of non-advanced adenoma, 79 cases (16.81%) of polyps were detected. The detection rate of intestinal lesions was 75.11% and indicated significant differences in gender and age. 20 CRCs included 15 of stage 0-I, 4 of stage Ⅱ-Ⅲ and 1 of unknown stage. The CT value of m SDC2 was negatively correlated with the proportion of advanced colorectal neoplasms ( χ2=16.063, P<0.001). The total cost of the screening was 4.339 5 million yuan, the screening benefit was 28.506 2 million yuan, and the benefit-cost ratio was 6.57. Conclusion:The CRC screening strategy of fecal m SDC2 detection combined with colonoscopy has high colonoscopy compliance and detection rate of intestinal lesions, which is conducive to the detection of early CRCs, and has good cost-effectiveness. This study suggests that this method may be applied to the general CRC screening in China and contribute to the prevention of CRC. The CT value of m SDC2 may have a certain suggestion on the malignant degree of intestinal tumors.
10.Porphyromonas gingivalis promotes the occurrence of esophageal squamous cell carcinoma via an inflammatory microenvironment
Haijun XU ; Yijun QI ; Dangrou WU ; Qiwei LIU ; Pan CHEN ; Mengxiang LI ; Yelin JIAO ; Haojie RUAN ; Zhitao LI ; Shegan GAO
Chinese Journal of Oncology 2024;46(8):746-754
Objective:To investigate the role of an inflammatory microenvironment induced by Porphyromonasgingivalis ( P. gingivalis) in the occurrence of esophageal squamous cell carcinoma (ESCC) in mice. Methods:A total of 180 C57BL/6 mice were randomly divided into 6 groups, i.e. control group, P. gingivalis group, 4NQO group, 4NQO + P. gingivalis group, 4NQO + P. gingivalis + celecoxib group, and 4NQO + P. gingivalis + antibiotic cocktail (ABC, including metronidazole, neomycin, ampicillin, and vancomycin) group, with 30 mice in each group, using the random number table. All mice were normalized by treatment with ABC in drinking water for 2 weeks. In the following 2 weeks, the mice in the control group and the P. gingivalis group were given drinking water, while the other 4 groups were treated with 30 μg/ml 4NQO in the drinking water. In weeks 11-12, the mice in the P. gingivalis group, the 4NQO + P. gingivalis group, the 4NQO + P. gingivalis + celecoxib group, and the 4NQO + P. gingivalis + ABC group were subjected to ligation of the second molar in oral cavity followed by oral P. gingivalis infection thrice weekly for 24 weeks in weeks 11-34. In weeks 13-34, the mice in 4NQO + P. gingivalis+celecoxib group and 4NQO + P. gingivalis + ABC group were administered with celecoxib and ABC for 22 weeks, respectively. At the end of 34 weeks, gross and microscopic alterations were examined followed by RT-qPCR and immunohistochemistry to examine the expression profiles of inflammatory- and tumor-molecules in esophagi of mice. Results:At 34 weeks, 4NQO treatment alone did not affect the foci of papillary hyperproliferation, diseased area, and the thickness of the esophageal wall, but significantly enhanced the foci of hyperproliferation (median 1.00, P<0.05) and mild/moderate dysplasia (median 2.00, P<0.01). In addition, the expression levels of IL-6 [8.35(3.45,8.99)], IL-1β [6.90(2.01,9.72)], TNF-α [12.04(3.31,14.08)], c-myc [2.21(1.80,3.04)], pSTAT3, Ki-67, and pH2AX were higher than those in the control group. The pathological changes of the esophageal mucosa were significantly more overt in the 4NQO + P. gingivalis group in terms of the foci of papillary hyperproliferation (median 2.00), diseased area (median 2.51 mm 2), the thickness of the esophageal wall (median 172.52 μm), the foci of hyperproliferation (median 1.00, P<0.05), and mild/moderate dysplasia (median 1.00, P<0.01). In mice of the 4NQO + P. gingivalis group, the expression levels of IL-6 [12.27(5.35,22.08)], IL-1β [13.89(10.04,15.96)], TNF-α [19.56(6.07,20.36)], IFN-γ [11.37(8.23,20.07)], c-myc [2.62(1.51,4.25)], cyclin D1 [4.52(2.68,7.83)], nuclear pSTAT3, COX-2, Ki-67, and pH2AX were significantly increased compared with the mice in the control group. In mice of the 4NQO + P. gingivalis group, the diseased area, invasive malignant foci as well as pSTAT3 and pH2AX expression were significantly blunted by celecoxib. Treatment with ABC markedly reduced the papillary hyperproliferative foci, invasive malignant foci, and pSTAT3 expression but not pH2AX. Conclusions:P. gingivalis promotes the occurrence of esophageal squamous cell carcinoma in mice by inducing an inflammatory microenvironment primed with 4NQO induced DNA damage. Clearance of P. gingivalis with ABC or anti-inflammatory intervention holds promise for prevention of esophageal squamous cell malignant pathogenesis via blockage of IL-6/STAT3 signaling and amelioration of inflammation.


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