1.The mechanism of PTGES3/HSP90 in the medial prefrontal cortex regulating obesity-related cognitive impairment
Jinyan Wang ; Jia Hu ; Rui Hu ; Chunxia Huang ; Qi Xue
Acta Universitatis Medicinalis Anhui 2025;60(4):596-603
Objective :
To investigate the mechanism of prostaglandin E synthase 3(PTGES3)/heat shock protein 90(HSP90) in the medial prefrontal cortex regulating obesity-related cognitive dysfunction.
Methods:
This study consisted of clinical trials and animal experiments. In part one, obese patients scheduled for bariatric surgery, and healthy adults matching gender and age were recruited at the same time to reach 10 cases in each group. The cognitive level was assessed with trail making test part A(TMT-A) and victoria stroop tests(VST). Four-dimensional data-independent acquisition(4D-DIA) was used to screen the proteome changes in peripheral blood. In part two, forty SPF healthy male C57BL/6J mice were randomly divided into four groups: normal diet group(ND group), high fat diet induced obesity group(DIO group), DIO supplemented with the control virus group(DIO+Scramble group) and DIO supplemented with the interfering virus group(DIO+shPTGES3 group). The Morris water maze test was conducted to evaluate the cognitive behavior changes of the four groups of mice. The immunofluorescence staining was performed to detect the expression of PTGES3 and HSP90 in the medial prefrontal cortex and the activation of ionized calcium binding adapter molecule 1(IBA1)-labeled microglia.
Results:
In the case-control study, the cognitive function of obese patients significantly decreased, and the expression of PTGES3 in peripheral blood significantly increased, while the level of PTGES3 was negatively correlated with cognitive function. In animal experiments, compared with ND group, DIO group had significantly prolonged time reaching the target platform, otherwise, the residence time in the target quadrant was shortened in the Morris water maze test. Simultaneously, there were significant increase in the expression of PTGES3 and HSP90, and the activation of IBA1 in the medial prefrontal cortex. Compared with DIO+Scramble group, mice in the DIO+shPTGES3 group spent less time reaching the target platform, and stayed longer in the target quadrant. The expression and co-localization levels of PTGES3 and HSP90 in medial prefrontal cortex significantly decreased. The activation level of microglia cells was also attenuated by PTGES3 interference.
Conclusion
Obesity-related cognitive dysfunction may be attributed to PTGES3/HSP90 in the medial prefrontal cortex by mediating neural inflammation.
2. Mechanism of Dahuangtang pellets in regulating podocyte autophagy of diabetic nephropathy mice through AMPK/mTOR/ULK1 signaling pathway
Beibei SU ; Yonglin LIANG ; Chunxia XUE ; Pu ZHANG ; Xiaoli PEI ; Lixia YANG ; Xiangdong ZHU ; Xia YANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2024;29(3):260-269
AIM: To explore the intervention effect of Dahuangtang pellets (DHT) on diabetic nephropathy (DN) based on the AMP-activated protein kinase/mammalian target of rapamycin/unc-51-like kinase 1 (AMPK/mTOR/ULK1) signaling pathway. METHODS: Eight mice were randomly assigned to the model group, the dapagliflozin group, and the DHT (high, medium, and low dosage) group out of a total of 40 C57BL/KSJ-db/db (hereafter referred to as db/db) mice; another 10 C57BL/KSJ-db/dm mice were used as the normal group, saline was provided to the normal and model groups, and the mice in the treatment group received the appropriate medications. The medications were given for 10 consecutive weeks, once per day, to the mice in the treatment group. At weeks 0, 4, 8, and 10 of administration, fasting blood glucose (FBG) was assessed by drawing blood at a predetermined time from the tail vein; Urine samples were taken at 0, 5, and 10 weeks after treatment to evaluate the levels of albumin and creatinine, and the urinary albumin-creatinine ratio (ACR) was computed. After 10 weeks, mice in each group were assayed for 24 h total urine protein, serum creatinine (Scr), urea nitrogen (BUN) levels; Western blotting analysis was conducted to detect the expression of p-AMPK, p-mTOR, and p-ULK1, as well as the expression of autophagy related proteins homolog of yeast Atg6 (Beclin-1), autophagy-related proteins microtubule-associated protein 1 light chain 3 (LC3), P62 in renal tissue; Immunohistochemistry was used to measure the expression of podocyte lacunar membrane proteins (Nephrin, Podocin) in renal tissues; The pathological morphology of renal tissue was observed by light microscopy and transmission electron microscopy. RESULTS: Compared with the model group, FBG, ACR, and 24 h total urine protein were reduced in the dapagliflozin group and DHT groups of mice, and there was no statistically significant difference in Scr and BUN; In renal tissues, there is increased expression of p-AMPK and p-ULK1, decreased expression of p-mTOR, increased expression of LC3II / LC3I and Beclin-1, and decreased expression of P62 (P<0.01, P< 0.05); differentially upregulated in glomeruli are the podocyte lacunar membrane proteins Nephrin and Podocin (P<0.01, P<0.05); renal pathologic damage was reduced to varying degrees; transmission electron microscopy showed an increase in the number of autophagic vesicles and autophagic lysosomes. CONCLUSION: DHT can delay the development of DN by regulating the AMPK / mTOR / ULK1 signaling pathway, enhancing podocyte autophagy, and protecting glomeruli.
3.Mechanism of Dahuang Tangluo Pills in Improving Renal Inflammatory Injury in Diabetic Kidkdey Disease by Regulating AGEs/RAGE/IKK/NF-κB Pathway
Pu ZHANG ; Jianqing LIANG ; Xia YANG ; Min BAI ; Xiangdong ZHU ; Chunxia XUE ; Beibei SU ; Yunhui ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(20):77-85
ObjectiveTo explore the protective effects of Dahuang Tangluo pills on early diabetic kidkdey disease (DKD) in db/db mice. MethodEight db/m mice were selected as the control group. Forty male db/db mice were selected and blood samples were collected via tail vein to measure fasting blood glucose (FBG). Mice with FBG ≥ 16.7 mmol·L-1, increased urine output, and persistent albuminuria were considered successful in model establishment. After successful modeling, they were randomly divided into a model group, a dapagliflozin group (1.5 mg·kg-1·d-1), and high, medium, and low dose groups of Dahuang Tangluo pills (3.6, 1.8, 0.9 g·kg-1·d-1, respectively), with eight mice in each group. All medication groups were administered orally, while the control and model groups were given an equal amount of distilled water by gavage daily. After continuous administration for 10 weeks, the survival status of the mice was observed, and their body weight, FBG, and kidney function-related indicators were measured. Inflammatory indicators in renal tissues were determined by enzyme-linked immunosorbent assay (ELISA). Hematoxylin-eosin (HE) staining, Masson staining, and electron microscopy were used to observe the pathological changes in renal tissues in each group. Immunofluorescence was employed to examine the expression of advanced glycation end products (AGEs) and receptors for advanced glycation end products (RAGE) proteins. Real-time quantitative polymerase chain reaction (Real-time PCR) and Western blot were utilized to detect the gene and protein expression levels of AGEs, RAGE, inhibitor of nuclear factor-κB (NF-κB) kinase (IKK), and NF-κB in the renal tissues of mice in each group. ResultCompared with control group, the model group showed a significant increase in body weight, FBG, serum creatinine (SCr), urinary microalbumin/urine creatinine ratio (ACR), total cholesterol (TC), and triglycerides (TG) (P<0.05). The levels of intercellular adhesion molecule-1 (ICAM-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) in renal tissues were significantly elevated (P<0.05). Renal histopathological staining and electron microscopy revealed loose arrangement, gaps, structural disarray, mesangial proliferation, and significant fibrosis in renal tissues. Real-time PCR results showed a significant increase in the expression of RAGE, IKK, and NF-κB genes in renal tissues (P<0.05). Immunofluorescence results demonstrated a significant increase in the expression of AGEs and RAGE proteins in renal tissues (P<0.05). Western blot results showed a significant increase in the expression of AGEs, RAGE, IKK, and NF-κB proteins in renal tissues (P<0.05). After drug intervention, compared with model group, the dapagliflozin group and the high-dose Dahuang Tangluo pills group showed significant reductions in body weight, FBG, SCr, and ACR (P<0.05), and a significant decrease in TC in mouse serum (P<0.05), while the high-dose Dahuang Tangluo pills group showed a significant decrease in TG in mouse serum (P<0.05). All treatment groups showed a significant reduction in ICAM-1, IL-6, and TNF-α in renal tissues (P<0.05). Renal histopathological staining and electron microscopy showed improved kidney injury, decreased collagen fiber deposition, and reduced mesangial proliferation in all treatment groups. Real-time PCR results showed a significant decrease in the expression of RAGE, IKK, and NF-κB genes in the dapagliflozin group and the high- and medium-dose Dahuang Tangluo pills groups (P<0.05). Immunofluorescence results demonstrated a significant decrease in the expression of AGEs and RAGE proteins in the dapagliflozin group and the high- and medium-dose Dahuang Tangluo pills groups (P<0.05). Western blot results showed a significant decrease in the expression of AGEs, RAGE, IKK, and NF-κB proteins in the dapagliflozin group and the high- and medium-dose Dahuang Tangluo pills groups (P<0.05). ConclusionDahuang Tangluo pills can improve the pathological structure of the kidneys and reduce renal inflammation in DKD mice, possibly through inhibiting the AGEs/RAGE/IKK/NF-κB pathway.
4.Accuracy assessment of refractive status in patients implanted with extended depth of focus intraocular lens
Chunxia* YU ; Xiaoling* FANG ; Wenwen XUE ; Meng CHEN ; Shenyu BEN ; Jinhua TAO ; Yulan WANG
International Eye Science 2024;24(11):1821-1825
AIM: To evaluate the refractive status through computer refractometer and OPD-Scan III auto refractometer in cataract patients after extended depth of focus(EDOF)intraocular lens implantation.METHODS: Retrospective observational study. A total of 61 cases(76 eyes)that received phacomulsification and implanted with TECNIS® Symfony ZXR00 intraocular lens in Shanghai Eye Diseases Prevention & Treatment Center from May 2022 to May 2023 were collected. Measurements from the computer refractometer, OPD-Scan III auto refractometer, and subjective refraction, were taken from all patients on the same day postoperatively.RESULTS: There were statistical significant difference in sphere(S)and spherical equivalent(SE)readings from the computer refractometer and subjective refraction(all P<0.01), with mean differences of -0.67±0.37 D and -0.75±0.35 D, respectively, and the S and SE obtained from computer refractometer more incline to myopia than those from subjective refraction; there were statistical significant difference in computer refractometer and subjective refraction(P<0.01), with a relative small absolute difference(0.21±0.24 D). The S, cylinder(C)and SE of computer refractometer(S, C, SE)were positively correlated with subjective refraction(r=0.7994, 0.7929, and 0.8118, respectively, all P<0.01). Additionally, there were statistical significant differences in S, C and SE of OPD-Scan Ⅲ and subjective refraction(P<0.01), and the absolute differences of S(0.63±0.36 D), C(0.35±0.26 D)and SE(0.53±0.36 D)were small. Furthermore, the S, C and SE of OPD-Scan Ⅲ were positively correlated with subjective refraction(r=0.4410, 0.4982, 0.5224, all P<0.01).CONCLUSION: In patients who received implantation of EDOF lenses, the consistency of computer refractometer, OPD-Scan III auto refractometer and subjective refraction was good. The average difference of the S and SE obtained via computer refractometer was large, but both exhibited a myopic shift relative to those derived from subjective refraction, and the C values demonstrated minimal discrepancy. Furthermore, the differences between OPD-Scan III auto refractometer and subjective refraction were small, but the direction of the difference is unstable, sometimes it is myopic deviation, while sometimes it is hyperopic deviation.
5.Epidemiological characteristics of infectious diseases among the primary and secondary school students in Songjiang District, Shanghai, 2018‒2022
Guiling GAO ; Qing XUE ; Chao WANG ; Chunxia YAO
Shanghai Journal of Preventive Medicine 2024;36(10):958-962
ObjectiveTo analyze the incidence and epidemiological characteristics of infectious diseases among the primary and secondary school students in Songjiang District, Shanghai, and to provide a scientific basis for the prevention and control of infectious diseases in schools. MethodsDescriptive epidemiological methods were used to analyze the types and numbers of infectious diseases among students in Songjiang District from 2018 to 2022. Furthermore, the incidence, constituent ratios and incidence precedence of infectious diseases were calculated simultaneously. ResultsA total of 5 543 cases of student infectious diseases were reported in Songjiang District from 2018 to 2022, involving 17 types of infectious diseases, with an annual incidence rate of 11.38‰. The reported infectious diseases were mainly respiratory infectious diseases (77.72%), followed by intestinal infections (21.88%). Chickenpox, influenza, and hand-foot-mouth disease were the top three infectious diseases according to the incidence rate, with a total of 3 966 cases reported, accounting for 71.55% of the total cases. More male cases were reported than females with a gender ratio of 1.44∶1. Infectious diseases were most prevalent among students aged between 6~<13 years (4 383 cases, accounting for 79.07%). The distribution of infectious diseases among students showed two peaks: from November to December and April to May. Jiuting Town, Xinqiao Town, and Chedun Town were the top three subdistricts (towns) in terms of incidence rate. ConclusionThe situation of infectious disease prevention and control among the primary and secondary school students in Songjiang District is severe, and monitoring and prevention of infectious diseases among students should be strengthened, especially respiratory infectious diseases.
6.Exploration on the Intervention Effect and Mechanism of Guiqi Yiyuan Ointment Combined with Cisplatin on Lewis Lung Cancer Mice Based on lncRNA H19/miR-19b3p/FTH1 Axis
Chunxia XUE ; Jianqing LIANG ; Yuanyuan ZHANG ; Yinxia JIN ; Shang LI ; Pu ZHANG ; Nan YANG ; Jintian LI ; Juan LI
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(8):90-96
Objective To explore the inhibitory effect of Guiqi Yiyuan Ointment combined with cisplatin on Lewis lung cancer mice and its mechanism based on the lncRNA H19/miR-19b3p/FTH1 axis.Methods Totally 60 SPF grade male C57BL/6 mice were randomly selected as blank group,and Lewis lung cancer mouse model was replicated in the remaining 50 mice.The modeled mice were randomly divided into model group,cisplatin group,and TCM low-,medium-and high-dosage combined with cisplatin group,with 10 mice in each group.The cisplatin group was given intraperitoneal injection of cisplatin 5 mg/kg,while the TCM low-,medium-and high-dosage combined with cisplatin group were given Guiqi Yiyuan Ointment 1.75,3.5,7.0 g/kg by gavage combined with intraperitoneal injection of cisplatin 5 mg/kg,the blank group and model group were given equal volume of normal saline by gavage for 14 consecutive days.The general condition of mice was observed,the tumor mass of mice was measured,and the tumor inhibition rate,spleen index,and thymus index were calculated,HE staining was used to observe the pathological changes of tumor tissue,and the contents of malondialdehyde(MDA),reduced glutathione(GSH),hydrogen peroxide(H2O2),and ferrous ions(Fe2+)were detected in the tumor tissue,immunohistochemistry and Western blot were used to detect the expression of nuclear factor E2 related factor 2(Nrf2),glutathione peroxidase 4(GPX4),ferritin heavy chain 1(FTH1)and solute carrier family 7 member 11(SLC7A11)protein in tumor tissue,real time fluorescence quantitative PCR was used to detect the expression of lncRNA H19 and miR-19b3p mRNA in tumor tissue.Results Compared with the blank group,the body mass,spleen index and thymus index of mice in the model group were decreased(P<0.05).Compared with the model group,the mental state and tumor histopathological morphology of mice in each administration group were improved to different degrees,the tumor mass of mice was reduced(P<0.05),the spleen index and the thymus index of mice increased(P<0.05),tumor cell lysis,rupture,and decrease in quantity,the contents of MDA,H2O2,Fe2+in tumor tissue increased(P<0.05),while GSH content decreased(P<0.05),the expression of Nrf2,GPX4,FTH1,SLC7A11 protein in tumor tissue decreased(P<0.05),the lncRNA H19 mRNA expression decreased(P<0.05),miR-19b3p mRNA expression increased(P<0.05).Compared with the cisplatin group,the tumor mass of mice in TCM high-dosage combined with cisplatin group reduced(P<0.05),the body mass,spleen index and thymus index increased(P<0.05),the contents of MDA,H2O2,Fe2+in tumor tissue of mice increased(P<0.05),the content of GSH decreased(P<0.05),the expression of Nrf2,FTH1,SLC7A11,GPX4 protein expression decreased(P<0.05),lncRNA H19 mRNA expression decreased(P<0.05),miR-19b3p mRNA expression increased(P<0.05).Conclusion Guiqi Yiyuan Ointment combined with cisplatin can significantly inhibit the tumor of Lewis lung cancer mice,and its mechanism may be related to regulating the expression of ferroptosis molecules related to the lncRNA H19/miR-19b3p/FTH1 axis.
7.Effects of Guiqi Yiyuan Ointment Combined with Cisplatin on Regulating the AMPK/ULK1 Signaling Pathway in Tumor Tissue of Lewis Lung Cancer Bearing Mice
Shang LI ; Jianqing LIANG ; Yinxia JIN ; Nan YANG ; Chunxia XUE ; Juan LI ; Jintian LI
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(9):110-116
Objective To observe the anti-tumor effect and mechanism of Guiqi Yiyuan Ointment combined with cisplatin in Lewis lung cancer bearing mice based on AMPK/ULK1 signaling pathway.Methods The mice were inoculated with Lewis lung cancer cells to establish a subcutaneous tumor model in the right axillary subcutaneous area,and were randomly divided into blank group,model group,cisplatin group and Guiqi Yiyuan Ointment high-,medium-and low-dosage+cisplatin groups,with 10 mice in each group.The cisplatin group received intraperitoneal injection of 5 mg/kg(once every 7 days)cisplatin,while the Guiqi Yiyuan Ointment high-,medium-and low-dosage+cisplatin groups received gavage of 7.0,3.5 and 1.75 g/kg Guiqi Yiyuan Ointment on the basis of cisplatin group,once a day,for 14 consecutive days.HE staining was used to observe the morphology of tumor tissue,immunohistochemical method was used to detect the protein expression of p-AMPK and p-ULK1 in tumor tissue,transmission electron microscopy was used to observe the number of autophagosomes,RT-PCR was used to detect the expression of p62,Beclin-1,Atg5 and LC3 mRNA in tumor tissue,Western blot was used to detect the expression of Beclin-1,p62,Atg5,LC3 and AMPK/ULK1 signaling pathway proteins in tumor tissue.Results Compared with the model group,the tumor mass of mice in all administration groups decreased significantly(P<0.05);the tumor tissue showed patchy necrotic areas and an increase in the number of autophagosomes,the mRNA expressions of Beclin-1,Atg5,and LC3 increased,the protein expressions of Beclin-1,Atg5,LC3 Ⅱ/Ⅰ,AMPK,p-AMPK,ULK1 and p-ULK1 increased,and the expression of p62 mRNA and protein decreased(P<0.05).Compared with the cisplatin group,the tumor mass of mice in Guiqi Yiyuan Ointment high-,medium-dosage+cisplatin groups decreased(P<0.05),the tumor inhibition rate increased;the expressions of ULK1 protein and Atg5 mRNA in tumor tissue of Guiqi Yiyuan Ointment high-,medium-and low-dosage+cisplatin groups significantly increased(P<0.05),the expressions of Beclin-1 and LC3 mRNA in Guiqi Yiyuan Ointment high-,medium-dosage+cisplatin groups significantly increased(P<0.05),the expressions of Atg5,LC3 Ⅱ/Ⅰ,AMPK,p-AMPK and p-ULK1 protein significantly increased(P<0.05),and the expression of p62 protein significantly decreased(P<0.05),the expression of p62 mRNA in Guiqi Yiyuan Ointment high-dosage+cisplatin group significantly decreased(P<0.05),the expression of Beclin-1 protein significantly increased(P<0.05).Conclusion Guiqi Yiyuan Ointment combined with cisplatin may activate autophagy and inhibit subcutaneous tumor growth in Lewis lung cancer bearing mice through the AMPK/ULK1 signaling pathway.
8.Risk factors for postoperative nausea and vomiting in obese patients undergoing laparoscopic sleeve gastrectomy
Qianqian YU ; Ling DONG ; Jun CHENG ; Xinyue WANG ; Pan ZHU ; Minghu WANG ; Pengfei SHENG ; Yufan JIANG ; Lingling ZHOU ; Qi XUE ; Chunxia HUANG ; Ye ZHANG
Chinese Journal of Anesthesiology 2023;43(12):1428-1432
Objective:To retrospectively identify the risk factors for postoperative nausea and vomiting (PONV)in the obese patients undergoing laparoscopic sleeve gastrectomy(LSG).Methods:The medical records from the obese patients who underwent elective laparoscopic sleeve gastrectomy from January 2018 to July 2022 were retrospectively collected. PONV was defined according to the use of remedial antiemetics in the nursing record sheet, and the patients were divided into PONV group and non-PONV group according to the occurrence of PONV that required treatment. The logistic regression analysis was used to identify the risk factors for PONV after LSG.Results:A total of 1 264 obese patients were included in this study, and there were 263 patients in PONV group, and the incidence of PONV was 20.81%. According to the results of multifactorial logistic regression analysis, female( OR=1.533, 95% CI 1.007-2.334, P=0.046), higher level of serum alanine aminotransferase concentrations ( OR=1.006, 95% CI 1.002-1.009, P=0.001), higher level of C-reactive protein ( OR=1.013, 95% CI 1.005-1.022, P=0.001), general anesthesia combined with nerve block (general anesthesia combined with TAPB: OR=2.737, 95% CI 1.817-4.121, P<0.001; general anesthesia combined with other nerve block: OR=1.899, 95% CI 1.249-2.889, P=0.003) and intraoperative use of sufentanil ( OR=2.114, 95% CI 1.308-3.415, P=0.002) were independent risk factors for PONV( P<0.05). However, the higher level of serum follicle-stimulating hormone concentrations ( OR=0.941, 95% CI 0.895-0.988, P=0.015), intraoperative use of dexmedetomidine ( OR=0.640, 95% CI 0.417-0.982, P=0.041), and administration of prophylactic antiemetic medication (antiemetic drugs during operation OR=0.669, 95% CI 0.469-0.955, P=0.027; antiemetic drugs after operation OR=0.303, 95% CI 0.182-0.503, P<0.001; antiemetic drugs during and after operation OR=0.215, 95% CI 0.107-0.434, P<0.001) were protective factors for PONV. Conclusions:Female, higher levels of serum alanine aminotransferase and C-reactive protein, general anesthesia combined with nerve block and intraoperative use of sufentanil are independent risk factors for PONV, while higher levels of follicle-stimulating hormone, intraoperative use of dexmedetomidine and administration of prophylactic antiemetic medication are protective factors for PONV among obese patients undergoing LSG.
9.Predictive value of systemic inflammation response index before treatment for pathological complete response in patients with breast cancer undergoing neoadjuvant chemotherapy
Yonghong LIU ; Lingbo XUE ; Yang BAI ; Jian JIN ; Chunxia ZANG ; Bo ZHANG ; Jie LI
Journal of International Oncology 2022;49(4):210-215
Objective:To investigate the predictive value of systemic inflammation response index (SIRI) before treatment for pathological complete response (pCR) in patients with breast cancer undergoing neoadjuvant chemotherapy.Methods:The clinicopathological data of 119 patients with primary breast cancer undergoing neoadjuvant chemotherapy and subsequent breast-conserving or modified radical surgery from Cangzhou Central Hospital of Hebei Province between January 2010 to March 2020 were retrospectively analyzed, and patients were divided into pCR group ( n=19) and non-pCR group ( n=100) based on postoperative pathology. The SIRI before treatment between the two groups was compared. The patients were divided into SIRI≤0.25 ( n=10) , 0.26-0.50 ( n=42) , 0.51-0.75 ( n=29) , 0.76-1.00 ( n=19) , and >1.00 ( n=19) groups according the SIRI before treatment, and the pCR ratios of the five groups were compared. Spearman correlation analysis was applied to evaluate the relationship between SIRI before treatment and pCR, logistic regression analysis was used to identify the influencing factors of pCR for neoadjuvant chemotherapy in breast cancer patients, and receiver operating characteristic (ROC) curve was used to evaluate the predictive value of SIRI before treatment for pCR of neoadjuvant chemotherapy in breast cancer patients. Results:Tumor size ( Z=2.26, P=0.024) , axillary lymph node metastasis ( χ2=5.73, P=0.017) , human epidermal growth factor receptor-2 (HER-2) ( χ2=8.77, P=0.003) , Ki-67 ( Z=2.68, P=0.007) , cytological nuclear grade ( χ2=5.08, P=0.024) , neutrophil count before treatment ( Z=2.44, P=0.015) , monocyte/lymphocyte ratio before treatment ( Z=3.04, P=0.002) , and SIRI before treatment ( Z=3.29, P=0.001) had statistical differences between the pCR and non-pCR groups. The pCR ratios were 50% (5/10) in the SIRI ≤0.25 group, 21% (9/42) in the 0.26-0.50 group, 10% (3/29) in the 0.51-0.75 group, 11% (2/19) in the 0.76-1.00 group, and 0 (0/19) in the >1.00 group, with a statistic difference ( χ2=14.28, P=0.006) . SIRI before treatment was negatively related with pCR ( r=-0.30, P=0.001) . Univariate logistic regression analysis showed that tumor size ( OR=0.50, 95% CI: 0.28-0.89, P=0.019) , axillary lymph node metastasis ( OR=5.43, 95% CI: 1.19-24.83, P=0.029) , HER-2 ( OR=7.54, 95% CI: 1.65-34.36, P=0.009) , Ki-67 ( OR=1.03, 95% CI: 1.01-1.05, P=0.008) , cytological nuclear grade ( OR=0.20, 95% CI: 0.04-0.92, P=0.038) , neutrophil count before treatment ( OR=0.54, 95% CI: 0.32-0.92, P=0.023) , monocyte/lymphocyte ratio before treatment ( OR=0.00, 95% CI: 0.00-0.01, P=0.007) , and SIRI before treatment ( OR=0.03, 95% CI: 0.00-0.37, P=0.007) were influencing factors for pCR of neoadjuvant chemotherapy in breast cancer patients. Multivariate logistic regression analysis confirmed that tumor size ( OR=0.31, 95% CI: 0.14-0.72, P=0.007) , axillary lymph node metastasis ( OR=10.97, 95% CI: 1.35-89.61, P=0.025) , HER-2 ( OR=6.47, 95% CI: 1.18-35.65, P=0.032) , Ki-67 ( OR=1.04, 95% CI: 1.00-1.07, P=0.029) , cytological nuclear grade ( OR=7.87, 95% CI: 1.01-61.35, P=0.049) , and SIRI before treatment ( OR=0.03, 95% CI: 0.00-0.58, P=0.020) were independent influencing factors for pCR of neoadjuvant chemotherapy in breast cancer patients. The ROC curve showed that the area under the curve of SIRI before treatment for predicting pCR was 0.74 (95% CI: 0.65-0.82) , sensitivity was 68.0%, and specificity was 75.3%. The area under the curve of monocyte/lymphocyte ratio before treatment for predicting pCR was 0.72 (95% CI: 0.63-0.80) , sensitivity was 48.0%, and specificity was 84.2%. The area under the curve of neutrophil count before treatment for predicting pCR was 0.68 (95% CI: 0.59-0.76) , sensitivity was 61.0%, and specificity was 83.7%. Conclusion:SIRI before treatment may serve as a marker for predicting pCR in patients with breast cancer undergoing neoadjuvant chemotherapy, patients with low SIRI are more likely to obtain pCR.
10.Beneficial Effects of Celastrol on Immune Balance by Modulating Gut Microbiota in Experimental Ulcerative Colitis Mice
Li MINGYUE ; Guo WEINA ; Dong YALAN ; Wang WENZHU ; Tian CHUNXIA ; Zhang ZILI ; Yu TING ; Zhou HAIFENG ; Gui YANG ; Xue KAMING ; Li JUNYI ; Jiang FENG ; Sarapultsev ALEXEY ; Wang HUAFANG ; Zhang GE ; Luo SHANSHAN ; Fan HENG ; Hu DESHENG
Genomics, Proteomics & Bioinformatics 2022;20(2):288-303
Ulcerative colitis(UC)is a chronic inflammatory bowel disease caused by many factors including colonic inflammation and microbiota dysbiosis.Previous studies have indicated that celastrol(CSR)has strong anti-inflammatory and immune-inhibitory effects.Here,we investigated the effects of CSR on colonic inflammation and mucosal immunity in an experimental colitis model,and addressed the mechanism by which CSR exerts the protective effects.We characterized the ther-apeutic effects and the potential mechanism of CSR on treating UC using histological staining,intestinal permeability assay,cytokine assay,flow cytometry,fecal microbiota transplantation(FMT),16S rRNA sequencing,untargeted metabolomics,and cell differentiation.CSR administra-tion significantly ameliorated the dextran sodium sulfate(DSS)-induced colitis in mice,which was evidenced by the recovered body weight and colon length as well as the decreased disease activity index(DAI)score and intestinal permeability.Meanwhile,CSR down-regulated the production of pro-inflammatory cytokines and up-regulated the amount of anti-inflammatory mediators at both mRNA and protein levels,and improved the balances of Treg/Thl and Treg/Th1 7 to maintain the colonic immune homeostasis.Notably,all the therapeutic effects were exerted in a gut microbiota-dependent manner.Furthermore,CSR treatment increased the gut microbiota diversity and changed the compositions of the gut microbiota and metabolites,which is probably associated with the gut microbiota-mediated protective effects.In conclusion,this study provides the strong evidence that CSR may be a promising therapeutic drug for UC.


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