1.RNA binding protein LIN28B promotes chemosensitivity of colon cancer by regulating the synthesis and activity of glutathione
Ning NING ; Yeqing SONG ; Yichao YAN ; Lin CHEN ; Yankai ZHANG
Chinese Journal of General Surgery 2025;40(8):643-649
Objective:To explore the influence of LIN28B on chemosensitivity of colon cancer by regulating GSH.Methods:Functional enrichment analysis of LIN28B target genes was performed using database. The primary tumor tissues of colon cancer patients who received neoadjuvant chemotherapy at Department of Gastroenterology, Peking University International Hospital from Nov 2017 to May 2020 were collected, and their LIN28B levels were detected by immunohistochemistry. According to the tumor regression grade, they were divided into chemotherapy sensitive group and chemotherapy resistant group, and the difference of LIN28B expression between the two groups was compared. LIN28B overexpression and knockdown colon cancer cell lines were constructed, and the effect of LIN28B on the chemosensitivity of colon cancer cells was detected by MTT assay. Double luciferase reporting experiment and Western blot were used to detect the direct binding and regulation of LIN28B to mRNA of four GSH related enzymes. At the same time, the regulation of LIN28B on total GSH and reduced GSH was tested. Finally, by detecting the level of reactive oxygen species (ROS) γ-H2AX and Comet assay to analyze the potential impact of LIN28B on genomic instability.Results:GSH-related enzymes were highly enriched in LIN28B target genes. The expression of LIN28B was heterogeneous in colon cancer patients. Compared with the low expression group, the average survival time of patients with high expression of LIN28B was significantly increased [(50.2±2.9 )months vs. (31.1±4.0 )months, P=0.001], and the proportion of tumor regression grade 0-1 was significantly different (48.0% vs. 16.0%, P=0.032). The expression level of LIN28B in chemotherapy sensitive group was significantly higher than that in drug resistant group ( P<0.01). LIN28B overexpression significantly increased the chemosensitivity of HCT116 cells to 5-fluorouracil (5-Fu) and oxaliplatin (L-OPH). The synthesis and activity of GSH were further inhibited (all P<0.01). At the same time, the ROS level of LIN28B overexpression cells was significantly increased after treatment with L-OPH. The level of γ-H2AX was significantly increased, and the content of comet tail DNA was also significantly increased ( P<0.01). Conclusion:LIN28B may increase the chemosensitivity of colon cancer cells by directly inhibiting the expression of GSH related enzymes, resulting in the decrease of GSH synthesis and activity, the increase of ROS level and genomic instability.
2.Mechanisms of Neiyiting Decoction in Preventing Postoperative Recurrence of Endometriosis by Inhibiting Macrophage M1 Polarization Through the TREM1/TLR4/NF-κB Signaling Pathway
Lijuan LU ; Weiwei ZENG ; Jingwen WANG ; Lurong ZHANG ; Ying LIU ; Xueliang SUN ; Wen XU ; Xiaohui FANG ; Yichao YAN ; Qinhua XIA
Journal of Sichuan University (Medical Sciences) 2025;56(2):371-381
Objective The high post-surgery recurrence rate of endometriosis(EMs)has emerged as a challenge in the long-term manaagement of the condition.This study is aimed at investigating the mechanisms of Neiyiting(NYT)decoction in preventing postoperative recurrence of EMs.Methods An animal model of EMs postoperative recurrence and a model of endometrial stromal cells(hEM15A)cocultured with macrophages(RAW 264.7 cell line)were established for both in vivo and in vitro experiments.An autotransplantation method was used to establish a rat model of EMs.The rats were divided into 4 groups(6 rats per group)and received the corresponding treatments:a Model group receiving distilled water,a Gestrinone group receiving gestrinone at 0.325 mg/kg,a low-dose NYT(NYT-L)group receiving NYT decoction at 5.04 g/(kg-d),and a high-dose NYT(NYT-H)group receiving NYT decoction at 10.08 g/(kg-d).The treatment was administered for 3 weeks via intragastric gavage.In addition,6 SD rats were randomly selected for the control group(Control group),and were given distilled water for 3 weeks via intragastric gavage.The sizes and pathological changes of recurrent lesions in EMs rats were observed.Immunohistochemistry and qRT-PCR were performed to assess the expression of M1 macrophage marker CD86 protein and mRNA in vivo.Additionally,immunohistochemistry and qRT-PCR were used to assess the expression of indicator proteins related to the triggering receptor expressed on myeloid cells 1(TREM1)/Toll-like receptor 4(TLR4)/nuclear factor kappa B(NF-κB)signaling pathway and mRNA.The proliferation of hEM15A cells in the coculture experiment was observed.Flow cytometry was performed to determine the polarization of RAW264.7 macrophages,and qRT-PCR was used to determine the expression levels of inducible nitric oxide synthase(iNOS)and interleukin 1β(IL-1β)mRNA.Western blot was performed to determine the expression of signaling pathway-related indicator proteins in vitro.ELISA was performed to determine the levels of inflammatory factors in vitro.Results Compared with the Model group,the volume of recurrent lesions in the NYT-H group was reduced(P<0.01).Findings from the macrophage M1 polarization assessment showed that the expression levels of CD86 protein and mRNA in the recurrent lesions of the Model group were higher than those in the control group(P<0.01).The expression levels of CD86 protein and mRNA in the recurrent lesions of the NYT-H group were lower than those of the Model group(P<0.01).In addition,the RAW 264.7 cell experiment further verified that NYT decoction could reduce the number of CD86-positive macrophages induced by plasmids overexpressing TREM1 and reduce the expression of IL-1β and iNOS mRNA(P<0.01).The results of the hEM15A cell proliferation assay showed that NYT decoction down-regulated KI-67 protein expression in hEM15A cells induced by macrophage M1 polarization(P<0.01).The results of TREM1/TLR4/NF-κB signaling pathway showed that the protein and mRNA expression levels of TREM1,TLR4,and NF-κB in the recurrent lesions of the Model group were higher than those of the control group(P<0.01).Compared with those in the Model group,the protein and mRNA expression levels of TREM1,TLR4,and NF-κB in the recurrent lesions of the NYT-H group were lower(P<0.01).In addition,the coculture experiment of RAW264.7 and hEM15A cells further confirmed that NYT decoction reduced the expression of TREM1,TLR4,and P-P65 proteins(P<0.01).Conclusion NYT decoction can inhibit macrophage M1 polarization through the TREM1/TLR4/NF-κB signaling pathway,improve the inflammation level,and inhibit the formation of ectopic endometrial lesions,thereby preventing postoperative recurrence of EMs.
3.RNA binding protein LIN28B promotes chemosensitivity of colon cancer by regulating the synthesis and activity of glutathione
Ning NING ; Yeqing SONG ; Yichao YAN ; Lin CHEN ; Yankai ZHANG
Chinese Journal of General Surgery 2025;40(8):643-649
Objective:To explore the influence of LIN28B on chemosensitivity of colon cancer by regulating GSH.Methods:Functional enrichment analysis of LIN28B target genes was performed using database. The primary tumor tissues of colon cancer patients who received neoadjuvant chemotherapy at Department of Gastroenterology, Peking University International Hospital from Nov 2017 to May 2020 were collected, and their LIN28B levels were detected by immunohistochemistry. According to the tumor regression grade, they were divided into chemotherapy sensitive group and chemotherapy resistant group, and the difference of LIN28B expression between the two groups was compared. LIN28B overexpression and knockdown colon cancer cell lines were constructed, and the effect of LIN28B on the chemosensitivity of colon cancer cells was detected by MTT assay. Double luciferase reporting experiment and Western blot were used to detect the direct binding and regulation of LIN28B to mRNA of four GSH related enzymes. At the same time, the regulation of LIN28B on total GSH and reduced GSH was tested. Finally, by detecting the level of reactive oxygen species (ROS) γ-H2AX and Comet assay to analyze the potential impact of LIN28B on genomic instability.Results:GSH-related enzymes were highly enriched in LIN28B target genes. The expression of LIN28B was heterogeneous in colon cancer patients. Compared with the low expression group, the average survival time of patients with high expression of LIN28B was significantly increased [(50.2±2.9 )months vs. (31.1±4.0 )months, P=0.001], and the proportion of tumor regression grade 0-1 was significantly different (48.0% vs. 16.0%, P=0.032). The expression level of LIN28B in chemotherapy sensitive group was significantly higher than that in drug resistant group ( P<0.01). LIN28B overexpression significantly increased the chemosensitivity of HCT116 cells to 5-fluorouracil (5-Fu) and oxaliplatin (L-OPH). The synthesis and activity of GSH were further inhibited (all P<0.01). At the same time, the ROS level of LIN28B overexpression cells was significantly increased after treatment with L-OPH. The level of γ-H2AX was significantly increased, and the content of comet tail DNA was also significantly increased ( P<0.01). Conclusion:LIN28B may increase the chemosensitivity of colon cancer cells by directly inhibiting the expression of GSH related enzymes, resulting in the decrease of GSH synthesis and activity, the increase of ROS level and genomic instability.
4.A survey on the current situation of serum vitamin A and vitamin D levels among children aged 2-<7 years of 20 cities in China
Qionghui WU ; Qian CHEN ; Ting YANG ; Jie CHEN ; Li CHEN ; Xueli XIANG ; Feiyong JIA ; Lijie WU ; Yan HAO ; Ling LI ; Jie ZHANG ; Xiaoyan KE ; Mingji YI ; Qi HONG ; Jinjin CHEN ; Shuanfeng FANG ; Yichao WANG ; Qi WANG ; Tingyu LI
Chinese Journal of Pediatrics 2024;62(3):231-238
Objective:To investigate serum vitamin A and vitamin D status in children aged 2-<7 years in 20 cities in China.Methods:A cross-sectional study was conducted. A total of 2 924 healthy children aged 2-<7 years were recruited from September 2018 to September 2019 from 20 cities in China, categorized by age groups of 2-<3 years, 3-<5 years, and 5-<7 years. The demographic and economic characteristics and health-related information of the enrolled children were investigated. Body weight and height were measured by professional staff members. The serum vitamin A and vitamin D levels were detected by high-performance liquid chromatography-tandem mass spectrometry. Chi-square test and Logistic regression were applied to analyze the association between vitamin A and vitamin D deficiency and insufficiency as well as their underlying impact factors.Results:The age of the 2 924 enrolled children was 4.33 (3.42, 5.17) years. There were 1 726 males (59.03%) and 1 198 females (40.97%). The prevalences of vitamin A and vitamin D deficiency in enrolled children were 2.19% (64/2 924) and 3.52% (103/2 924), respectively, and the insufficiency rates were 29.27% (856/2 924) and 22.20% (649/2 924), respectively. Children with both vitamin A and vitamin D deficiencies or insufficiencies were found in 10.50% (307/2 924) of cases. Both vitamin A ( χ2=7.91 and 8.06, both P=0.005) and vitamin D ( χ2=71.35 and 115.10, both P<0.001) insufficiency rates were higher in children aged 3-<5 and 5-<7 years than those in children aged 2-<3 years. Vitamin A and vitamin D supplementation in the last 3 months was a protective factor for vitamin A and D deficiency and insufficiency, respectively ( OR=0.68 and 0.22, 95% CI 0.49-0.95 and 0.13-0.40, both P<0.05). The rates of vitamin A and D insufficiency was higher in children with annual household incomes <60 000 RMB than in those with annual household incomes ≥60 000 RMB ( χ2=34.11 and 10.43, both P<0.01). Northwest and Southwest had the highest rates of vitamin A and vitamin D insufficiency in children aged 2-<7 yeas, respectively ( χ2=93.22 and 202.54, both P<0.001). Conclusions:Among 20 cities in China, children aged 2-<7 years experience high rates of vitamin A and vitamin D insufficiency, which are affected by age, family economic level, vitamin A and vitamin D supplementation, and regional economic level. The current results suggest that high level of attention should be paid to vitamin A and vitamin D nutritional status of preschool children.
5.Therapeutic effect of ultrasound-guided erector spinae plane block combined with dexmedetomidine on postherpetic neuralgia
China Modern Doctor 2024;62(21):34-37
Objective This investigation evaluates the effectiveness of ultrasound-guided erector spinae plane block,employing a combination of ropivacaine,methylprednisolone sodium succinate,mecobalamin,and an additional administration of dexmedetomidine(Dex),in the treatment of postherpetic neuralgia.Methods A tatol of 60 postherpetic neuralgia patients who underwent erector spinae plane block at Shangyu People's Hospital of Shaoxing City from May 2023 to March 2024 were selected.To divided patients into control group and Dex group using random number table method,30 cases in each group.Besides conventional medication therapy,both groups received the ultrasound-guided erector spinae plane block.The patients in control group were administered a mixed diluent of ropivacaine,mecobalamin,and methylprednisolone sodium succinate,while the patients in Dex group received an additional dosage of Dex at 1 μg/kg.The pain,depression,and anxiety scores were compared between two groups.Results Both groups reported a decrease in pain scores at the end of the first week and second weeks and two weeks after the completion of treatment,compared to pre-treatment levels.The decrease in pain scores in Dex group was significantly greater than that in control group,with a statistically significant difference(P<0.05).After treatment,the depression and anxiety scores of both groups of patients decreased compared to pre-treatment.The scores of the patients in Dex group improved more significantly compared to the patients in control group,and the difference was statistically significant(P<0.05).Conclusion The ultrasound-guided erector spinae plane block,augmented with dexmedetomidine,effectively reduces the intensity of pain in postherpetic neuralgia patients and alleviates their symptoms of anxiety and depression.
6.Impact on analgesic efficacy and safety of esketamine as an adductor canal block adjuvant in knee arthroplasty
Yan ZHANG ; Yichao CAI ; Na CAO ; Huiru YANG ; Xinghua BIAN ; Kan LI
Adverse Drug Reactions Journal 2024;26(11):672-676
Objective:To explore the impact on analgesic efficacy and safety of esketamine as an adductor canal block adjuvant in knee arthroplasty.Methods:The study was a prospective, single center, randomized controlled trial. The subjects were patients who received knee arthroplasty in Zhangjiakou First hospital from October 2021 to October 2023. The patients were randomly divided into trial group and control group using a random number table method. The patients in the both groups received general anesthesia and postoperative patient-controlled intravenous analgesia (PCIA). The patients in the trial group were injected with 0.375% ropivacaine combined with esmketamine, while those in the control group were only injected with 0.375% ropivacaine. The postoperative vital signs, quadriceps femoris muscle strength, resting and dynamic visual analogue scale (VAS) pain score, use of PCIA, and incidence of postoperative adverse reactions in patients between the 2 groups were compared.Results:A total of 120 patients were included in this study, with 60 cases in each group. There were no significant differences in heart rate, mean arterial pressure, respiratory rate, and body temperature in patients between the trial group and the control group at 24 and 48 hours after operation (all P>0.05). There were no significant differences in quadriceps femoris muscle strength at 12, 24 and 48 hours after operation (all P>0.05). At rest, the VAS pain score at 12 hours after operation in the trial group was lower than that in the control group [(2.89±0.49) points vs. (3.36±0.23) points], the difference was statistically significant ( P<0.05). In the active state, the VAS scores at 12 and 24 hours after operation in the trial group were lower than those in the control group [(3.78±0.41) points vs. (4.11±0.45) points, (3.79±0.56) points vs. (4.19±0.69) points], the differences were statistically significant (all P<0.05). The number of times of PCIA compression 24 hours after operation in the experimental group was less than that in the control group [(5.35±1.03) times vs. (7.89±1.34) times], and the difference was statistically significant ( P<0.05), the sensory block time in the experimental group was longer than that in the control group [(488.26±57.75) min vs. (92.26±65.15) min], and the difference was statistically significant ( P<0.05). There were no significant differences in total incidence of adverse reactions including nausea, vomiting, urinary retention, dizziness, drowsiness, delirium and hallucination in patients between the 2 groups within 1 week after operation (all P>0.05). Conclusion:Esketamine as an adjuvant of ropivacaine for adductor block can alleviate the pain level of patients undergoing knee arthroplasty, and it has good safety.
7.Impact on analgesic efficacy and safety of esketamine as an adductor canal block adjuvant in knee arthroplasty
Yan ZHANG ; Yichao CAI ; Na CAO ; Huiru YANG ; Xinghua BIAN ; Kan LI
Adverse Drug Reactions Journal 2024;26(11):672-676
Objective:To explore the impact on analgesic efficacy and safety of esketamine as an adductor canal block adjuvant in knee arthroplasty.Methods:The study was a prospective, single center, randomized controlled trial. The subjects were patients who received knee arthroplasty in Zhangjiakou First hospital from October 2021 to October 2023. The patients were randomly divided into trial group and control group using a random number table method. The patients in the both groups received general anesthesia and postoperative patient-controlled intravenous analgesia (PCIA). The patients in the trial group were injected with 0.375% ropivacaine combined with esmketamine, while those in the control group were only injected with 0.375% ropivacaine. The postoperative vital signs, quadriceps femoris muscle strength, resting and dynamic visual analogue scale (VAS) pain score, use of PCIA, and incidence of postoperative adverse reactions in patients between the 2 groups were compared.Results:A total of 120 patients were included in this study, with 60 cases in each group. There were no significant differences in heart rate, mean arterial pressure, respiratory rate, and body temperature in patients between the trial group and the control group at 24 and 48 hours after operation (all P>0.05). There were no significant differences in quadriceps femoris muscle strength at 12, 24 and 48 hours after operation (all P>0.05). At rest, the VAS pain score at 12 hours after operation in the trial group was lower than that in the control group [(2.89±0.49) points vs. (3.36±0.23) points], the difference was statistically significant ( P<0.05). In the active state, the VAS scores at 12 and 24 hours after operation in the trial group were lower than those in the control group [(3.78±0.41) points vs. (4.11±0.45) points, (3.79±0.56) points vs. (4.19±0.69) points], the differences were statistically significant (all P<0.05). The number of times of PCIA compression 24 hours after operation in the experimental group was less than that in the control group [(5.35±1.03) times vs. (7.89±1.34) times], and the difference was statistically significant ( P<0.05), the sensory block time in the experimental group was longer than that in the control group [(488.26±57.75) min vs. (92.26±65.15) min], and the difference was statistically significant ( P<0.05). There were no significant differences in total incidence of adverse reactions including nausea, vomiting, urinary retention, dizziness, drowsiness, delirium and hallucination in patients between the 2 groups within 1 week after operation (all P>0.05). Conclusion:Esketamine as an adjuvant of ropivacaine for adductor block can alleviate the pain level of patients undergoing knee arthroplasty, and it has good safety.
8.Indocyanine green and nanocarbon lymph node tracing in laparoscopic radical resection for right colon cancer
Yankai ZHANG ; Yichao YAN ; Ning NING
Chinese Journal of General Surgery 2023;38(3):167-172
Objective:To compare the lymph node tracing of indocyanine green (ICG) and nanocarbon in laparoscopic right hemicolectomy.Methods:Fifty-two patients with right colon cancer were randomly divided into two groups: ICG group and nanocarbon group at Peking University International Hospital between Oct 2020 and Jul 2022. Sentinel lymph node (SLN) mapping and standard oncologic resection was performed. The micrometastasis was to detect when the routine SLN pathological test was negative.Results:In ICG group, the detection rate of SLN was 100%, the sensitivity was 93%, the false negative rate was 7%, and the accuracy was 96%,which were better than nanocarbon group (92%,57%,43%,77%). The number of SLN and positive SLN detected in ICG group were significantly higher than nanocarbon group [(3.2±0.7) vs. (2.6±1.1), t=4.424, P=0.020; (1.2±1.2) vs.(0.5±0.8), t=15.176, P=0.013]. The SLN biopsy accuracy of patients with BMI ≥24 kg/m 2 and tumor diameter ≥3 cm in ICG group was significantly higher than nanocarbon group (90% vs. 44%, χ 2=7.935, P=0.005; 90% vs.57%, χ 2=4.309, P=0.038). The detection rate of micrometastasis in SLN of ICG group was significantly different from nanocarbon group (35% vs. 15%, χ 2=5.853, P=0.016). Conclusion:ICG fluorescence imaging is superior to nanocarbon in SLN biopsy during laparoscopic radical right hemicolectomy, especially when patients' BMI ≥24 kg/m 2 and tumor diameter ≥3 cm.
9.Clinicopathology and prognosis of alpha fetoprotein-producing gastric carcinoma
Kaisheng XU ; Yongbai LI ; Jintang HUANG ; Shaoyong WANG ; Zhongmin ZHANG ; Yichao YAN
Chinese Journal of General Surgery 2021;36(8):585-590
Objective:To analyze the clinicopathological features and prognostic factors of alpha‐fetoprotein‐producing gastric carcinoma (AFPGC).Methods:A retrospective analysis was made on 2 671 GC patients admitted from Jan 1998 to Dec 2018 , AFPGC patients and matching AFP negative GC cases were enrolled and their clinicopathological features and prognostic factors were analyzed. The survival curve was drawn by Kaplan-Meier method. Log-rank test was used to test the significance, Univariate analysis was performed by using COX proportional hazard model.Results:There were 98 AFPGC in this study accounting for 4.5% of all GC of the corresponding time period. The proportion of male to female was 2.16∶1, the average age was (65±12) years. The serum AFP levels significantly decreased after operation in most patients (median: 52 ng/ml vs. 5 ng/ml, Z=-2.736, P=0.001). Serum AFP and CEA levels in patients with AFPGC before treatment were significantly higher than that in patients with AFP negative GC (both P<0.05) . Vascular invasion(62.71% vs. 40.68%) and liver metastasis (31.63% vs .6.12%) were more likely to occur in AFPGC groups (both P<0.05). However, there was no significant difference between the two groups in tumor size, location, differentiation and lymph node metastasis (all P>0.05). The prognosis of AFPGC was significant pooer than that in AFP negative GC ( P<0.05). Prognosis of AFPGC patients was significantly correlated with preoperative serum AFP level, TNM stage, lymph node metastasis, simultaneous liver metastasis and vascular invasion (all P<0.05) . COX multivariate survival analysis found that preoperative serum AFP level was independent risk factors of patients with AFPGC ( P<0.05). Conclusion:AFPGC is a special GC charactering poor prognosis .
10.Expression of vasohibin-1 and VEGF-A and its clinical significance in gastric cancer
Yichao YAN ; Chao SHEN ; Ning NING ; Yankai ZHANG ; Wenyue WANG ; Yingjiang YE ; Shan WANG
Chinese Journal of General Surgery 2021;36(8):612-615
Objective:To explore the expression of vasohibin-1 (VASH1) and vascular endothelial growth factor A (VEGF-A) and clinical significance of VASH1 in gastric carcinoma.Methods:The expression of VASH1 and VEGF-A were detected by immunohistochemistry in formalin-fixed and paraffin-embedded sections in 56 pairs of gastric cancer and corresponding paraneoplastic tissue specimens. The correlation between the expression of VASH1, VEGF-A, clinicopathological parameters and prognosis were analyzed.Results:VASH1 and VEGF-A expression was significantly higher in gastric cancer tissues than normal paraneoplastic tissues. VASH1 and VEGF-A protein were expressed in 79% and 82% of gastric cancer tissues, respectively. A positive correlation was found between Vasohibin-1 and VEGF-A expression in gastric cancer tissues. VASH1 expression has significant positive correlation with TNM stage, tumor stromal invasion, tumor gross types and distant metastasis. Patients with high VASH1 expression had significantly worse overall survival (OS) and progression-free survival (PFS) than those with low VASH1 expression.Conclusion:VASH1 might be a clinically relevant predictor of patients in gastric cancer.

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