1.Astragalus Mongholicus Bunge-Curcuma Aromatica-Paridis Rhizoma Inhibits Metastasis of Colon Cancer via the PERK/eIF2α/ATF4 Signaling Pathway
Huilan ZHANG ; Wenhui GUO ; Tingting SU ; Si CHEN ; Qianhui YU ; Qihang YIN ; Linlu WAN ; Xu WANG ; Decai TANG
Journal of Nanjing University of Traditional Chinese Medicine 2024;40(3):240-248
OBJECTIVE To investigate the mechanism of anti-colorectal cancer growth and metastasis-related effects of Astraga-lus mongholicus Bunge-Curcuma aromatica-Paridis Rhizoma(Qi-Zhu-Zao)pairing through PERK/eIF2α/ATF4 signaling pathway mediating endoplasmic reticulum stress.METHODS Twenty-four BALB/c male mice were randomly divided into sham-operated group,model group,5-FU(5-fluorouracil)group(25 mg·kg-1),and Qi-Zhu-Zao high dose group(5.85 g·kg-1),Qi-Zhu-Zao low dose group(2.925 g·kg-1)(n=6)to construct a mouse model of colorectal cancer in situ transplantation tumor,and the inter-vention effect of Qi-Zhu-Zao combination on tumor growth was assessed by the change of tumor volume size after 15 days of administra-tion;the intervention effect of Qi-Zhu-Zao combination on tumor growth was assessed by H&E.Pathological staining was used to eval-uate the effect of Qi-Zhu-Zao combination on the liver and tumor tissues of mice.The changes of MDA,SOD and GSH-Px levels were detected by enzyme-linked immunosorbent assay(ELISA);the expression of PERK/eIF2α/ATF4 signaling pathway and EMT-related proteins were detected by protein immunoblotting(Western blot).RESULTS Compared with the model group,the tumor volume was significantly reduced(P<0.000 1),liver and spleen metastases were less pronounced in the Qi-Zhu-Zao high-dose group,and his-topathological staining results of liver tissue and tumor produced changes in oxidative stress indicators SOD,MDA,and GSH-Px,up-regulation of ER stress-related proteins p-PERK,p-IF2α,and ATF4,etc.,upregulated the protein expression levels of E-Cadherin,downregulated N-Cadherin,Vimentin,and Snail,and inhibited the EMT process(P<0.01 or P<0.05).CONCLUSION In this paper,we investigated the regulatory mechanism related to the inhibition of colorectal cancer growth and metastasis by the combination of Qi-Zhu-Zao trigonal medicine,and demonstrated that it may inhibit the growth and metastasis of colorectal cancer by activating the PERK/eIF2α/ATF4 pathway to induce sustained ER stress and affect the EMT process of colorectal cancer.
2.Efficacy of entecavir versus tenofovir disoproxil fumarate in treatment of chronic hepatitis B patients with high viral load
Huikun ZHOU ; Jianning JIANG ; Minghua SU ; Rongming WANG ; Bobin HU ; Deli DENG ; Huilan WEI ; Xianshuai LIANG ; Wenming HE ; Rongsheng GUO
Journal of Clinical Hepatology 2022;38(3):532-536
Objective To investigate the efficacy of entecavir (ETV) versus tenofovir disoproxil fumarate (TDF) and the treatment measures for poor response in previously untreated chronic hepatitis B (CHB) patients with high viral load. Methods A total of 165 CHB patients who received antiviral therapy and met the inclusion criteria in Department of Infectious Diseases, The First Affiliated Hospital of Guangxi Medical University, from June 2016 to July 2021 were enrolled. The patients enrolled had a baseline HBV DNA level of > 6lg copies/ml and were previously untreated CHB patients who had used ETV or TDF for 48 weeks, and quantitative real-time PCR was used to measure HBV DNA. Virologic response rate was calculated after 48 weeks of treatment; a logistic regression analysis was used to investigate the influencing factors for the response of HBV DNA < 500 copies/mL and HBV DNA < 100 copies /mL at 48 weeks; a stratified analysis was performed to compare the virologic response rate of HBV DNA < 500 copies /ml and HBV DNA < 100 copies/ml after 48 weeks between the patients with different ages, sexes, baseline HBV DNA levels, baseline alanine aminotransferase (ALT) levels, types of first-line medication, and HBeAg statuses. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups, the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups, and the binary logistic regression model was used for multivariate analysis. Results After 48 weeks of treatment, 85.5% (141/165) of the patients achieved an HBV DNA load of < 500 copies/mL, and 66.1% (109/165) of the patients achieved an HBV DNA load of < 100 copies /mL, with no significant difference in treatment outcome between the ETV group and the TDF group. The multivariate logistic regression analysis showed that sex( OR =2.793, 95% CI : 1.197-6.517), baseline HBV DNA( OR =0.369, 95% CI : 0.142-0.959), baseline ALT( OR =4.556, 95% CI : 1.770-11.732), and baseline HBeAg( OR =0.120, 95% CI : 0.033-0.429) were influencing factors for complete virologic response(all P < 0.05). For the patients with normal ALT (≤40 U/L) at baseline, 75.6% (34/45) achieved an HBV DNA load of < 500 copies/mL after 48 weeks of treatment, and 53.3% (24/45) achieved an HBV DNA load of < 100 copies/mL, with no significant difference in treatment outcome between the ETV group and the TDF group. For the patients with abnormal ALT (> 40 U/L) at baseline, 89.2% (107/120) achieved an HBV DNA load of < 500 copies/mL after 48 weeks of treatment, and the proportion of such patients in the TDF group was significantly higher than that in the ETV group (96.1% vs 84.1%, χ 2 =4.386, P =0.036); 70.8% (85/120) achieved an HBV DNA load of < 100 copies/mL, the proportion of such patients was no significant difference between the TDF group and the ETV group (78.4% vs 65.2%). The response of HBV DNA < 100 copies/ml of the normal baseline ALT group and the abnormal baseline ALT group, there were no significant differences between the patients aged≤30 years and aged > 30 years (77.8% vs 47.2%, 85.2% vs 66.7%). For the patients who did not achieve complete virologic response (HBV DNA ≥100 copies/mL) after 48 weeks of treatment, 87.9% (29/33) achieved complete virologic response after the original treatment regimen was prolonged for 48 weeks, and 100% (9/9) of the patients achieved complete virologic response after switching to or adding the first-line nucleos(t)ide analogues (NUCs) without cross-resistance sites with the original regimen for another 48 weeks. Conclusion The patients aged > 30 years should receive antiviral therapy as early as possible, regardless of viral load and ALT level, especially those with a family history of liver cirrhosis or hepatocellular carcinoma; the patients aged ≤30 years who have a normal ALT level and a high viral load should consider initiating antiviral therapy after providing informed consent. For the patients with poor response after 48 weeks of treatment, first-line NUCs without cross-resistance sites with the original regimen should be switched to or added in time.
3.Research progress on low carbohydrate diet in the control of overweight and obesity
LU Yanyu ; GUO Huilan ; SHEN Fang ; HUANG Xiaoxu ; ZHANG Pianhong
Journal of Preventive Medicine 2021;33(12):1231-1235
Overweight and obesity are main risk factors for chronic metabolic diseases, and are strongly associated with the increased risk of premature death. Low carbohydrate diet (LCD) has been proven to effectively control body weight and fat mass in overweight and obese patients by short-term (≤6 months) dietary intervention studies. The mechanisms include regulation of energy metabolism, anti-inflammatory, antioxidant, alteration in expression of lipid metabolic-related genes and modulation of intestinal flora. However, the conclusions are inconsistent on whether LCD can cause durable weight loss and reduce the risk of overweight and obesity. This review summarizes the current research progress on the mechanisms, epidemiological studies, intervention studies and potential risks of LCD in controlling overweight and obesity, providing a reference for the future research and clinical application.
4.Research progress on plant-based diets for the prevention and management of chronic kidney disease
Huilan GUO ; Yanyu LU ; Xiaoxu HUANG ; Pianhong ZHANG
Journal of Public Health and Preventive Medicine 2021;32(5):126-129
Diet management is the key part in the prevention and treatment of chronic kidney disease (CKD). A plant-based diet is a diet consisting mostly or entirely of foods derived from plants, with little or no animal foods. In recent years, research on plant-based diets for chronic kidney disease has been increasing. Large-scale epidemiological studies and interventional studies consistently suggest that plant-based diets could reduce the risk of CKD and related complications and slow down CKD progression. This article reviews the research progress of plant-based diets in the prevention and control of CKD.
5.Detection of Chlamydia trachomatis DNA in urine and urethral/cervical swab samples: analysis of results from 1 475 outpatients attending sexually transmitted disease clinics
Huanli WANG ; Bin YANG ; Qing GUO ; Zijian GONG ; Kang ZENG ; Wenlin YANG ; Ruihua FANG ; Huilan ZHU ; Chao BI ; Wanping HE ; Ridong YANG ; Shaokai TANG ; Jianqin WANG
Chinese Journal of Dermatology 2021;54(9):814-818
Objective:To compare the detection rate of genital Chlamydia trachomatis (CT) DNA between urine and urethral/cervical swab samples. Methods:From December 2018 to December 2019, a total of 1 475 outpatients were collected from sexually transmitted disease clinics in 7 medical institutions, such as Department of Venereology, Guangzhou Institute of Dermatology, including 1 118 males and 357 females. One urethral/cervical swab sample and one urine sample were collected successively from each patient. Real-time fluorescence-based PCR was performed to detect CT DNA in urine and urethral/cervical swab samples, and paired chi-square test was used to compare the positive rate of CT DNA between the 2 kinds of samples. Random- or fixed-effect meta-analysis was conducted for the test of heterogeneity and merging of positive rates of CT DNA in the urine and urethral/cervical swabs among 7 medical institutions.Results:The positive rate of CT DNA in the urine samples was significantly higher than that in the swab samples from 4 medical institutions (all P < 0.05) , while there was no significant difference in the positive rate of CT DNA between the 2 kinds of samples from 3 medical institutions (all P > 0.05) . The heterogeneity ( I2) estimates of the CT-DNA positive rate in urine and swab samples among different medical institutions were 78.6% (95% CI: 55.9% - 89.6%) and 73.7% (95% CI: 43.7% - 87.7%) , respectively; meta-analysis showed that the total merged positive rate of CT DNA in the urine samples was 10.8% (95% CI: 7.2% - 15.9%) , which was significantly higher than that in the swab samples (7.8%, 95% CI: 4.9% - 12.1%; χ2 = 39.2, P < 0.05) . Compared with the swab sample-based CT-DNA detection method, the sensitivity, specificity, positive predictive value, negative predictive value and consistency rate of the urine sample-based CT-DNA detection method were 97.0% (128/132) , 96.3% (1 293/1 343) , 71.9% (128/178) , 99.7% (1 293/1 297) , and 96.3% (1 421/1 475) , respectively. The positive rate of CT DNA in the urine samples from 1 118 male patients was 11.0% (95% CI: 7.2% - 16.5%) , which was significantly higher than that in the swab samples (7.6%, 95% CI: 4.9% - 11.8%; χ2 = 34.3, P < 0.05) . There was no significant difference in the positive rate of CT DNA between the urine (11.9%, 95% CI: 7.7% - 17.9%) and cervical swab samples from 357 female patients (10.4%, 95% CI: 7.6% - 14.0%; χ2 = 3.2, P > 0.05) . Conclusions:The positive rate of CT DNA in urine samples is higher than or similar to that in urethral/cervical swab samples. The urine sample-based CT-DNA detection method has characteristics of convenience, non-invasiveness, painlessness and low cost, and is worthy of clinical promotion.
6. Expression of myocyte enhancer factor 2B in mantle cell lymphoma and its clinical significance
Fang LIU ; Qing LIU ; Na GUO ; Ganmei ZHANG ; Yuanfei DENG ; Weiwei HU ; Huilan RAO
Chinese Journal of Pathology 2020;49(1):40-46
Objective:
To investigate the expression of myocyte enhancer factor 2B (MEF2B) in mantle cell lymphomas (MCL), and to analyze the correlation between the expression of MEF2B and pathological subtypes, structural subtypes, SOX11 expression and its clinical significance.
Methods:
Paraffin-embedded tissues were stained with HE, immunohistochemistry (EnVision method) and fluorescence in situ hybridization (FISH) , in addition, the clinical and pathological data of 60 cases of MCL were collected at Sun Yat-sen University Foshan Hospital and Sun Yat-sen University Cancer Center from January,2002 to May, 2019 for analysis.
Results:
Of the 60 MCLs, males is predominant (M∶F
7. Clinicopathological features of T-lymphoblastic lymphoma with Langerhans cell histiocytosis in the same lymph node
Fang LIU ; Huilan RAO ; Na GUO ; Li GUO ; Jin LYU ; Weiwei HU ; Xiaoge ZHOU
Chinese Journal of Pathology 2020;49(2):149-155
Objective:
To investigate the clinicopathological features, immunophenotypes, genetics and prognosis of T-lymphocyte lymphoma/myeloid sarcoma combined with Langerhans cell histiocytyosis (coexistence of T-LBL/MS and LCH).
Methods:
Clinical and pathological data of the 6 patients with coexistence of T-LBL/MS and LCH were analyzed, who were diagnosed at the Foshan Hospital of Sun Yat-sen University and the Friendship Hospital of Capital Medical University, from December 2013 to April 2019. The hematoxylin and eosin stain, immunohitochemistry (EnVision) and in situ hybridization were used. Related literatures were reviewed.
Results:
Four patients were T-LBL combined with LCH, 1 was T-LBL/MS combined with LCH, and 1 was MS combined with LCH. There were 2 male and 4 female patients, with age ranged from 5 to 77 years old (median, 59 years old). Three patients represented with only multiple lymph node swelling. The other 3 displayed both multiple lymph node swelling, and skin/liver or spleen lesions. Lymph node structure was destroyed in 5 cases, while 3 cases had several residual atrophic follicles. Histologically, there were two types of tumor cells: one type of the abnormal lymphoid-cells exhibited small to medium-sized blast cells, typically showing a nested distribution, and these cells were mainly identified in residual follicles and paracortical areas; the other type of histiocytoid cells had a large cell size and abundant pale or dichromatic cytoplasm. Their nuclei were irregularly shaped, showing folded appearance and nuclear grooves. These cells were mainly present in marginal sinus, medullary sinus and interstitial area between follicles. Eosinophil infiltration in the background was not evident in any of the cases. The lymphoid-cells of medium size showed TdT+/CD99+/CD7+, with variable expression of CD34/MPO/CD2/CD3. Ki-67 index was mostly 30%-50%. However, the histiocytoid cells showed phenotype of CD1a+/S-100+/Langerin+/-, while CD163/CD68 were positive in some degree. These cells did not express any T or B cell markers. The Ki-67 index mostly ranged between 10%-20%. None of the cases had Epstin-Barr viral infection. Among the 6 patients, 4 patients were followed up (6-63 months, median time, 18.5 months), of whom 1 patient died of the disease and 3 patients were alive at the end of follow-up.
Conclusions
T-LBL/MS combined with LCH is a rare mixed type of immature hematopoietic disease, and mainly occurs in lymph node and skin. The clinical course is overall aggressive. Therefore, it is helpful to recognize and identify the two pathologic components in the same tissue for accurate diagnosis and proper treatment.
8.Liver histological status and clinic outcome in HBeAg-negative chronic hepatitis B with low viral load
Deli DENG ; Jianning JIANG ; Minghua SU ; Rongming WANG ; Weiwei ZANG ; Xiaozhang LING ; Huilan WEI ; Xianshuai LIANG ; Huikun ZHOU ; Wenming HE ; Rongsheng GUO
Chinese Journal of Hepatology 2020;28(12):1013-1017
Objective:To retrospectively analyze the serological, virological, biochemical, liver histological status and clinical outcomes in HBeAg-negative chronic hepatitis B (CHB) patients with low HBV viral load, and to explore the necessity of antiviral therapy for these patients.Methods:A total of 99 HBeAg-negative CHB patients with HBV DNA level < 4 lg copies/ml who performed liver biopsy at the baseline were enrolled from the follow-up cohort. Among them, 23 cases received the second liver biopsy during follow-up. The relationships among the degree of inflammation and fibrosis of liver tissues, the status of HBsAg and HBcAg, age, gender, family history, HBV DNA load, serological markers and other indicators were analyzed. The pathological differences between two liver biopsy examinations were compared. The effect of nucleos(t)ide analogues (NAs) treatment on patient’s clinical outcomes were analyzed. For multivariate analysis, a binary logistic regression model was performed. Log-rank test was used to compare the cumulative incidence of hepatocellular carcinoma (HCC) in NAs-treated and non-NA streated patients.Results:Baseline liver histology status showed that 58.6% (58/99) patients had obvious liver tissue damage in their baseline liver tissue pathology (G≥2 and /or S≥2). Univariate logistic regression analysis showed that a liver cirrhosis (LC) family history, a HBsAg-positive family history, baseline alanine aminotransferase and aspartate aminotransferase levels were positively correlated factors for liver tissue damage. Multivariate logistic regression analysis showed that a LC family history was the main risk factor for liver tissue damage. Twenty-three cases had received a second liver biopsy after an interval of 4.5 years. In 10 untreated cases, the second liver biopsy results showed the rate of obvious liver tissue damage (G≥2 and/ or S≥2) increased from 50.0% to 90.0%. In the other 13 cases who received NAs treatment, the second liver biopsy showed improvement in liver histology, and the rate of obvious liver tissue damage decreased from 61.5% to 46.2%. The 5-year HCC cumulative incidence in non-NAs-treated patients was significantly higher than that of in NAs-treated patients (17.7% vs. 3.8%, P = 0.046). Conclusion:For most HBeAg-negative CHB patients with low viral load, liver tissue pathology result suggests that it meets the indications for antiviral therapy, especially in patients with a LC familial history. Without antiviral therapy, liver tissue damage for these patients will progressively worse with the high incidence of HCC. Therefore, it is suggested that antiviral therapy should be started as soon as possible for the HBeAg-negative CHB patients with low viral load regardless of the alanine aminotransferase level, especially in patients over 30 years-old with a LC or HCC family history.
9. Clinicopathologic features of primary mucosal CD30-positive T-cell lymphoproliferative disorders in head and neck region
Fang LIU ; Min LI ; Liangyun ZHANG ; Li GUO ; Weiwei HU ; Huilan RAO
Chinese Journal of Pathology 2018;47(6):412-416
Objective:
To study clinicopathologic features, prognosis and differential diagnoses of primary mucosal CD30-positive T-cell lymphoproliferative disorders of the head and neck(mCD30+ TLPD-head and neck).
Methods:
Three cases of mCD30+ TLPD-head and neck were collected from January 2014 to April 2017 at Sun Yat-Sen University Foshan Hospital. A literature review of mCD30+ TLPD of head and neck was provided.
Results:
All three cases presented with either bulging/exophytic nodule or mucosal ulcer/erosion. Morphologically, the tumor consisted of diffuse proliferation of uniform, large atypical mononuclear lymphoid cells that showed irregular or polymorphic nuclei with small nucleoli, and abundant pale or amphophilic cytoplasm. Hallmark cells with eccentric, horseshoe, kidney-like, or doughnut-shaped nuclei were present. While mitotic figures were present, no tumor necrosis was found. Eosinophilc infiltration was obvious in the background. The atypical large lymphoid cells had a immunophenotype of CD30+ /CD3+ /CD4+ /CD56- along with positive cytotoxic molecule. While being negative for EBER/ALK/CD20/CD8, TCR rearrangement was found in 2 out of 3 cases. Three patients were cured after excision without relapse and metastasis.The two patients with TCR rearrangement didn′t show aggressive clinical course.
Conclusions
mCD30+ TLPD-head and neck is a rare benign lymphoproliferative disorder with spontaneous regression. It should be differentiated from cutaneous CD30+ anaplstic large cell lymphoma, lymphomatoid papulosis, and EBV-related mucocutaneous ulcer. Correct recognition of mCD30+ TLPD of head and neck is important to avoid overtreatment.
10.Relationships of psychological and social factors on dyspepsia of the college students in Nanning city
Guowen ZUO ; Jingjing QI ; Liexin LIANG ; Huilan YE ; Xianwen GUO ; Facan ZHANG
Chinese Journal of Digestion 2016;36(4):259-264
Objective To investigate the prevalence of dyspepsia and the relationship between dyspepsia,psychological and social factors among the college students in Naning city,and to improve the prevention and treatment of dyspepsia in this region.Methods Rome Ⅲ diagnostic questionnaire for adult dyspepsia,Chinese college student mental health scale (CCSMHS),Chinese college student psychological stress scale (CCSPSS),Chinese college student adaptation scale (CCSAS) and Chinese college student personality scale (CCSPS) were performed through interview survey in 2 580 Nanning college students.Chi square test and rank sum test were used to compared differences between groups.Correlation analysis was performed by Pearson correlation and Logisitic regression analysis.Results A total of 2 520 qualified Rome m questionnaires were recovered.The prevalence of dyspepsia in Nanning college students was 5.36%(135/2 520).The most common appearance of dyspepsia in college students were dislike of drinking tea (86.96%(100/115) vs 79.10%(1 605/2 029)),dislike of pickled food (85.22%(98/115) vs 76.29%(1 548/2 029)) and missing meals (40.87%(47/115) vs 30.31%(615/2 029)),the differences were statistically significant (x2 =4.122,4.860,5.685;all P<0.05),while the dyspepsia was not related with drinking,smoking and taking raw,cold or spicy food (all P>0.05).The results of multifactor regression analysis showed that the prevalence of dyspepsia was not correlated with diet.Among the twelve dimensions of psychological health,the somatization,anxiety,depression,low self-esteem,social withdrawal,sexual psychology,paranoia,force,dependency,psychotic tendencies of dyspepsia group were significantly higher than those with non-dyspepsia group (x2 =16.981,21.805,12.520,13.539,6.998,6.154,15.013,9.457,10.715,4.260,all P<0.05).Among the seven dimensions of psychological stress,study pressure and development pressure were negative life events,and their of dyspepsia group were significantly higher than those with non-dyspepsia group (x2 =6.216,Fisher exact probability test,both P<0.05).There was no statistically significant difference between two groups in the seven personality,such as active,outgoing,tenacity,rigorous,altruism,affectionate and easy-going (all P>0.05).Among the seven dimensions of adaptation,the adaptation to campus life,emotion and career choice of dyspepsia group were significantly lower than those with non-dyspepsia group (x2 =8.223,8.148,5.713,all P<0.05).While there was no statistically significant difference between two groups in the other four dimensions of adaption,such as relationships,learning,ego and satisfaction (all P>0.05).The results of Logistic regression analysis in psychological health,stress and adaption of dyspepsia group and non-dyspepsia group indicated that dyspepsia was associated with somatization (odds ration (OR) =1.610,95% confidence interval (CI) 1.012-2.559),anxiety (OR=1.955,95%CI 1.216-3.142) and the study pressure (OR=2.159,95%CI 1.106-4.213).The results of Pearson correlation analysis in study pressure,somatization and anxiety of dyspepsia group showed that both somatization and anxiety were correlated with study stress in dyspepsia group (r=0.314,0.323;both P<0.05).Conclusions Dyspepsia is a common symptom in Nanning college students.Students with dyspepsia have different degrees of psychological problems which are mostly anxiety and somatization.And study stress as a negative event is the major stress factor.


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