1. Resveratrol promotes autophagy through zinc ion and induces cardiomyocyte protection
Pei WANG ; Jin-Kun XI ; Hu MA ; Ying YANG ; You-Cheng HU ; Tian-Yu LIU ; Jia-Bao GUO ; Yong-Gui HE
Chinese Pharmacological Bulletin 2023;39(6):1048-1054
Aim To investigate whether resveratrol (Resveratrol, Res) induces cardiomyocyte protection by increasing intracellular zinc ion and its possible signal mechanism. Methods H9c2 cells were routinely cultured and 2-deoxyglucose (2-DG) was used to establish an endoplasmic reticulum stress (ERS) model. The experiment was randomly divided into control group, 2-DG group, Res +2-DG group, TPEN + Res + 2-DG group and 3-MA + Res +2-DG group. Cell viability was detected by MTT and CCK-8; the expression levels of ERS molecular chaperone proteins glucose-regulated protein 78 (GRP78), glucose-regulated protein 94 (GRP94) and autophagy proteins LC3 II / I, p62 and p-AMPK were detected by Western blot; the expression of LC3 protein was measured by cellular immunofluorescence; the mitochondrial membrane potential (Aijjm) and the intracellular zinc ion level were measured by laser scanning confocal microscope. Results Compared with the control group, 2-DG reduced cell activity and resveratrol inhibited the changes caused by 2-DG, which was reversed by zinc chelator TPEN. 2-DG increased GRP78 and GRP94 expression and resveratrol inhibited the protein changes caused by 2-DG, which was reversed by TPEN. 2-DG increased the expression of LC3 II / I, p-AMPK and decreased the expression of p62, and resveratrol promoted the effect of 2-DG. 2-DG increased the fluorescence intensity of LC3, and resveratrol enhanced the effect of 2-DG, which was reversed by TPEN and 3-MA. 2-DG reduced the red fluorescence intensity of mitochondrial TMRE and green fluorescence intensity of intracellular zinc ions, and resveratrol inhibited these changes caused by 2-DG, which was also reversed by TPEN and 3-MA. The above differences were all statistically significant (P < 0. 05). Conclusion Resveratrol increases intracellular zinc to promote ERS-induced autophagy and prevent the mPTP opening in H9c2 cardiac cells.
2.Mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 regimen in the treatment of pediatric Burkitt lymphoma.
Meng ZHANG ; Pan WU ; Yan Long DUAN ; Ling JIN ; Jing YANG ; Shuang HUANG ; Ying LIU ; Bo HU ; Xiao Wen ZHAI ; Hong Sheng WANG ; Yang FU ; Fu LI ; Xiao Mei YANG ; An Sheng LIU ; Shuang QIN ; Xiao Jun YUAN ; Yu Shuang DONG ; Wei LIU ; Jian Wen ZHOU ; Le Ping ZHANG ; Yue Ping JIA ; Jian WANG ; Li Jun QU ; Yun Peng DAI ; Guo Tao GUAN ; Li Rong SUN ; Jian JIANG ; Rong LIU ; Run Ming JIN ; Zhu Jun WANG ; Xi Ge WANG ; Bao Xi ZHANG ; Kai Lan CHEN ; Shu Quan ZHUANG ; Jing ZHANG ; Chun Ju ZHOU ; Zi Fen GAO ; Min Cui ZHENG ; Yonghong ZHANG
Chinese Journal of Pediatrics 2022;60(10):1011-1018
Objective: To analyze the clinical characteristics of children with Burkitt lymphoma (BL) and to summarize the mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen. Methods: Clinical features of 436 BL patients who were ≤18 years old and treated with the CNCL-B-NHL-2017 regimen from May 2017 to April 2021 were analyzed retrospectively. Clinical characteristics of patients at disease onset were analyzed and the therapeutic effects of patients with different clinical stages and risk groups were compared. Survival analysis was performed by Kaplan-Meier method, and Cox regression was used to identify the prognostic factors. Results: Among 436 patients, there were 368 (84.4%) males and 68 (15.6%) females, the age of disease onset was 6.0 (4.0, 9.0) years old. According to the St. Jude staging system, there were 4 patients (0.9%) with stage Ⅰ, 30 patients (6.9%) with stage Ⅱ, 217 patients (49.8%) with stage Ⅲ, and 185 patients (42.4%) with stage Ⅳ. All patients were stratified into following risk groups: group A (n=1, 0.2%), group B1 (n=46, 10.6%), group B2 (n=19, 4.4%), group C1 (n=285, 65.4%), group C2 (n=85, 19.5%). Sixty-three patients (14.4%) were treated with chemotherapy only and 373 patients (85.6%) were treated with chemotherapy combined with rituximab. Twenty-one patients (4.8%) suffered from progressive disease, 3 patients (0.7%) relapsed, and 13 patients (3.0%) died of treatment-related complications. The follow-up time of all patients was 24.0 (13.0, 35.0) months, the 2-year event free survival (EFS) rate of all patients was (90.9±1.4) %. The 2-year EFS rates of group A, B1, B2, C1 and C2 were 100.0%, 100.0%, (94.7±5.1) %, (90.7±1.7) % and (85.9±4.0) %, respectively. The 2-year EFS rates was higher in group A, B1, and B2 than those in group C1 (χ2=4.16, P=0.041) and group C2 (χ2=7.21, P=0.007). The 2-year EFS rates of the patients treated with chemotherapy alone and those treated with chemotherapy combined with rituximab were (79.3±5.1)% and (92.9±1.4)% (χ2=14.23, P<0.001) respectively. Multivariate analysis showed that stage Ⅳ (including leukemia stage), serum lactate dehydrogenase (LDH)>4-fold normal value, and with residual tumor in the mid-term evaluation were risk factors for poor prognosis (HR=1.38,1.23,8.52,95%CI 1.05-1.82,1.05-1.43,3.96-18.30). Conclusions: The CNCL-B-NHL-2017 regimen show significant effect in the treatment of pediatric BL. The combination of rituximab improve the efficacy further.
Adolescent
;
Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
;
Burkitt Lymphoma/drug therapy*
;
Child
;
Disease-Free Survival
;
Female
;
Humans
;
Lactate Dehydrogenases
;
Lymphoma, B-Cell/drug therapy*
;
Male
;
Prognosis
;
Retrospective Studies
;
Rituximab/therapeutic use*
;
Treatment Outcome
3.A 10-year retrospective analysis of spectrums and treatment options of orthostatic intolerance and sitting intolerance in children.
Ya Xi CUI ; Jun Bao DU ; Qing You ZHANG ; Ying LIAO ; Ping LIU ; Yu Li WANG ; Jian Guang QI ; Hui YAN ; Wen Rui XU ; Xue Qin LIU ; Yan SUN ; Chu Fan SUN ; Chun Yu ZHANG ; Yong Hong CHEN ; Hong Fang JIN
Journal of Peking University(Health Sciences) 2022;54(5):954-960
OBJECTIVE:
To analyze the disease spectrums underlying orthostatic intolerance (OI) and sitting intolerance (SI) in Chinese children, and to understand the clinical empirical treatment options.
METHODS:
The medical records including history, physical examination, laboratory examination, and imagological examination of children were retrospectively studied in Peking University First Hospital from 2012 to 2021. All the children who met the diagnostic criteria of OI and SI were enrolled in the study. The disease spectrums underlying OI and SI and treatment options during the last 10 years were analyzed.
RESULTS:
A total of 2 110 cases of OI and SI patients were collected in the last 10 years, including 943 males (44.69%) and 1 167 females (55.31%) aged 4-18 years, with an average of (11.34±2.84) years. The overall case number was in an increasing trend over the year. In the OI spectrum, postural tachycardia syndrome (POTS) accounted for 826 cases (39.15%), followed by vasovagal syncope (VVS) (634 cases, 30.05%). The highest proportion of SI spectrum was sitting tachycardia (STS) (8 cases, 0.38%), followed by sitting hypertension (SHT) (2 cases, 0.09%). The most common comorbidity of OI and SI was POTS coexisting with STS (36 cases, 1.71%). The highest proportion of treatment options was autonomic nerve function exercise (757 cases, 35.88%), followed by oral rehydration salts (ORS) (687 cases, 32.56%), metoprolol (307 cases, 14.55%), midodrine (142 cases, 6.73%), ORS plus metoprolol (138 cases, 6.54%), and ORS plus midodrine (79 cases, 3.74%). The patients with POTS coexisting with VVS were more likely to receive pharmacological intervention than the patients with POTS and the patients with VVS (41.95% vs. 30.51% vs. 28.08%, χ2= 20.319, P < 0.01), but there was no significant difference in the proportion of treatment options between the patients with POTS and the patients with VVS.
CONCLUSION
POTS and VVS in children are the main underlying diseases of OI, while SI is a new disease discovered recently. The number of children with OI and SI showed an increasing trend. The main treatment methods are autonomic nerve function exercise and ORS. Children with VVS coexisting with POTS were more likely to take pharmacological treatments than those with VVS or POTS only.
Child
;
Electrolytes
;
Female
;
Humans
;
Male
;
Metoprolol
;
Midodrine
;
Orthostatic Intolerance/therapy*
;
Postural Orthostatic Tachycardia Syndrome/diagnosis*
;
Retrospective Studies
;
Salts
;
Sitting Position
;
Syncope, Vasovagal/diagnosis*
;
Tilt-Table Test
4.Correlations between alterations of T-helper 17 cells and treatment efficacy after concurrent radiochemotherapy in locally advanced cervical cancer (stage IIB-IIIB): a 3-year prospective study.
Yi LIU ; Qiu-Fen GUO ; Jin-Long CHEN ; Xi-Rui LI ; Fei HOU ; Xiao-Yan LIU ; Wen-Jing ZHANG ; Yan ZHANG ; Fu-Feng GAO ; You-Zhong ZHANG ; Bao-Xia CUI ; Nai-Fu LIU
Chinese Medical Journal 2021;134(8):954-962
BACKGROUND:
Recently, T-helper 17 (Th17) cells have been proved to play an important role in promoting cervical cancer. But, till now, few study has been carried out to understand the involvement of these cells in efficacy of anti-tumor treatments. This study aimed to investigate the alterations in the percentage of circulating Th17 cells and related cytokines in locally advanced cervical cancer (LACC) patients before and after concurrent chemoradiotherapy (cCRT) and to analyze the correlations between the alterations in Th17 cells and treatment efficacy.
METHODS:
A prospective study with 49 LACC (International federation of gynecology and obstetrics [FIGO] stage IIB-IIIB) patients and 23 controls was conducted. Patients received the same cCRT schedule and were followed up for 3 years. Circulating Th17 cells (CD3+CD8- interleukin [IL]-17+ T cells) and related cytokines IL-17, transforming growth factor-β (TGF-β), IL-10, IL-23, IL-6, and IL-22 were detected before and after cCRT. Correlations between alterations of circulating Th17 cells and treatment efficacy were analyzed. Kaplan-Meier analysis was used for overall survival (OS) and progression-free survival (PFS).
RESULTS:
We found that 40 patients finished the entire cCRT schedule and met the endpoint of this study. The percentage of circulating Th17 cells in the LACC patients was higher than that in the controls, and it significantly decreased after cCRT (P < 0.05). After cCRT, patients were divided into two groups based on the average of the Th17 cells declined. The subgroup of patients with a prominent decrease in circulating Th17 cells after cCRT had a higher treatment efficacy and longer PFS and OS times. Compared with the control patients, LACC patients had higher IL-6, IL-10, IL-22, TGF-β levels and a lower IL-23 level (P < 0.05). After cCRT, IL-6, IL-10, IL-17, IL-23 level significantly increased and TGF-β level significantly decreased compared with the levels before cCRT (P < 0.05).
CONCLUSION
Circulating Th17 cells in the LACC patients (FIGO stage IIB-IIIB) were higher than those in the controls, but they generally decreased after cCRT. A more pronounced decrease in circulating Th17 cells after cCRT was correlated with better therapeutic effect and longer PFS and OS times.
Chemoradiotherapy
;
Disease-Free Survival
;
Female
;
Humans
;
Neoplasm Staging
;
Prospective Studies
;
Retrospective Studies
;
Th17 Cells
;
Treatment Outcome
;
Uterine Cervical Neoplasms/therapy*
5.Analysis of pertussis surveillance 2017 to 2019 in Minhang District of Shanghai
Yan DU ; Jia REN ; Li-ping ZHANG ; Xi WANG ; Bao-fang JIN ; Ye WANG ; Ke-wen MEI ; Xiu-hong TIAN
Shanghai Journal of Preventive Medicine 2021;33(11):1040-1045
Objective:To analyze the source of infection, clinical symptoms and epidemiological characteristics of pertussis surveillance cases in Minhang District of Shanghai from 2017 to 2019,so as to provide the basis for pertussis surveillance and immunization strategy. Methods:Descriptive epidemiological method was used to analyze the pertussis surveillance cases. Results:A total of 334 cases were included in the pertussis active surveillance system, 237 cases were confirmed cases. There were 13 towns or streets in Minhang District, except for Pujin Street, all the other 12 towns or streets had cases. The high risk group (131/237, 55.27% of the cases) were the infants under five months old who did not reach the age of immunization or did not complete the basic immunization of diphtheria, tetanus, and acellular pertussis combined vaccine (DTaP). The cases mainly occurred in March to July, accounting for 71.31% (169/237). The highest culture-positive rate of
6.A double-blind, randomized, placebo- and positive-controlled phase III trial of 1% benvitimod cream in mild-to-moderate plaque psoriasis.
Lin CAI ; Gen-Hui CHEN ; Qian-Jin LU ; Min ZHENG ; Yu-Zhen LI ; Jin CHEN ; Jie ZHENG ; Fu-Ren ZHANG ; Jian-Bin YU ; Sen YANG ; Fu-Qiu LI ; Sheng-Xiang XIAO ; Qiu-Ning SUN ; Jin-Hua XU ; Xing-Hua GAO ; Hong FANG ; Tian-Wen GAO ; Fei HAO ; Quan-Zhong LIU ; Ya-Ting TU ; Ruo-Yu LI ; Bao-Xi WANG ; Dan-Qi DENG ; Qing-Shan ZHENG ; Hong-Xia LIU ; Jian-Zhong ZHANG
Chinese Medical Journal 2020;133(24):2905-2909
BACKGROUND:
Benvitimod cream, a novel synthetic small molecule, was effective in treating mild-to-moderate plaque psoriasis. We conducted a phase III clinical trial to assess the efficacy and safety of benvitimod cream in patients with mild-to-moderate plaque psoriasis.
METHODS:
We randomly assigned 686 patients (2:1:1) to receive 1% benvitimod cream, 0.005% calcipotriol ointment or placebo twice a day for 12 weeks. The primary efficacy end points were the percentage of patients with a 75% or greater reduction from baseline in the psoriasis area and severity index (PASI 75) score and with a score of 0 or 1 in static physician's global assessment (sPGA) at week 12.
RESULTS:
The results showed that 50.4% of patients in the benvitimod group achieved PASI 75, which was significantly higher than that in the calcipotriol (38.5%, P < 0.05) and placebo (13.9%, P < 0.05) groups. The proportion of patients achieving an sPGA score 0 or 1 was 66.3% in the benvitimod group and 63.9% in the calcipotriol group, which were both significantly higher than that in the placebo group (34%, P < 0.05). In the long-term follow-up study, 50.8% of patients experienced recurrence. After retreatment with 1% benvitimod, 73.3% of patients achieved an sPGA score of 0 or 1 again at week 52. Adverse events included application site irritation, follicular papules, and contact dermatitis. No systemic adverse reactions were reported.
CONCLUSION:
During this 12-week study, benvitimod cream was demonstrated with high effectiveness and safety in patients with mild-to-moderate plaque psoriasis.
TRIAL REGISTRATION
Chinese Clinical Trial Registry (ChiCTR), ChiCTR-TRC-13003259; http://www.chictr.org.cn/showprojen.aspx?proj=6300.
Double-Blind Method
;
Follow-Up Studies
;
Humans
;
Ointments
;
Psoriasis/drug therapy*
;
Resorcinols
;
Severity of Illness Index
;
Stilbenes
;
Treatment Outcome
7.A multicenter survey of antibiotic use in very and extremely low birth weight infants in Hunan Province.
Ming-Jie WANG ; Shao-Jie YUE ; Jin LIN ; Xi-Rong GAO ; Xiao-Ming PENG ; Meng-Yu CHEN ; Hua-Bao PENG ; Bei CAO ; Yun-Qing ZENG ; Shu-Lian WANG ; Bo WEN ; Xi-Lin HUANG ; Xiao-Ping LI ; Ai-Zhen ZHANG ; Ting CAO ; Yi-Hua CHEN ; Tie-Qiang CHEN ; Chun-Hua YE ; Tao BO ; De-Lin JIANG ; Xiu-Qun HUANG ; Na-Fang REN ; Long-Zhang TAO ; Fang YAO ; Chang-Jun TIAN ; Hong-Ming LI ; Ai-Min ZHANG ; Fu-Rong HUANG ; Wei-Guo ZHANG ; Xiang-Hong CHEN ; Yu-Chan LIU ; Zheng-Lin LIU ; Yan-Shan XU ; Jing-Song MING ; Li CHEN ; Ning-Yi ZHU ; Jun-Min HE ; Sai-Jun YI ; Tuan-Mei WANG ; Zhao-Hui LI ; Gui-Tian WANG
Chinese Journal of Contemporary Pediatrics 2020;22(6):561-566
OBJECTIVE:
To investigate the current status of antibiotic use for very and extremely low birth weight (VLBW/ELBW) infants in neonatal intensive care units (NICUs) of Hunan Province.
METHODS:
The use of antibiotics was investigated in multiple level 3 NICUs of Hunan Province for VLBW and ELBW infants born between January, 2017 and December, 2017.
RESULTS:
The clinical data of 1 442 VLBW/ELBW infants were collected from 24 NICUs in 2017. The median antibiotic use duration was 17 days (range: 0-86 days), accounting for 53.0% of the total length of hospital stay. The highest duration of antibiotic use was up to 91.4% of the total length of hospital stay, with the lowest at 14.6%. In 16 out of 24 NICUs, the antibiotic use duration was accounted for more than 50.0% of the hospitalization days. There were 113 cases with positive bacterial culture grown in blood or cerebrospinal fluid, making the positive rate of overall bacterial culture as 7.84%. The positive rate of bacterial culture in different NICUs was significantly different from 0% to 14.9%. The common isolated bacterial pathogens Klebsiella pneumoniae was 29 cases (25.7%); Escherichia coli 12 cases (10.6%); Staphylococcus aureus 3 cases (2.7%). The most commonly used antibiotics were third-generation of cephalosporins, accounting for 41.00% of the total antibiotics, followed by penicillins, accounting for 32.10%, and followed by carbapenems, accounting for 13.15%. The proportion of antibiotic use time was negatively correlated with birth weight Z-score and the change in weight Z-score between birth and hospital discharge (r=-0.095, -0.151 respectively, P<0.01), positively correlated with death/withdrawal of care (r=0.196, P<0.01).
CONCLUSIONS
Antibiotics used for VLBW/ELBW infants in NICUs of Hunan Province are obviously prolonged in many NICUs. The proportion of routine use of third-generation of cephalosporins and carbapenems antibiotics is high among the NICUs.
Anti-Bacterial Agents
;
Birth Weight
;
Humans
;
Infant
;
Infant, Extremely Low Birth Weight
;
Infant, Newborn
;
Intensive Care Units, Neonatal
;
Surveys and Questionnaires
8.Warm needling moxibustion versus electroacupuncture for simple obesity due to yang deficiency of the spleen and kidney: a controlled clinical trial
Li-Yan ZHOU ; Tian-Feng HE ; Xiao-Yan CHU ; Yin-Hua SONG ; Xing-Hong BING ; Jin-Lei DING ; Xi-Dong DUAN ; Yong-Bao LUO ; Yin SHI ; Shan-Ping TAO
Journal of Acupuncture and Tuina Science 2019;17(4):258-263
Objective: To compare the therapeutic efficacy between warm needling moxibustion and electroacupuncture (EA) in the treatment of simple obesity due to yang deficiency of the spleen and kidney. Methods: Seventy patients with simple obesity due to yang deficiency of the spleen and kidney were randomly divided into a warm needling moxibustion group and an EA group, with 35 subjects in each group. Same major acupoints were selected for the two groups, including Shuifen (CV 9), Guanyuan (CV 4), Daheng (SP 15), Shuidao (ST 28), Shousanli (LI 10), Zusanli (ST 36), Sanyinjiao (SP 6) and Taixi (KI 3). The warm needling moxibustion group received warm needling moxibustion, while the EA group received EA treatment. The interventions were performed once every other day, with 15 treatments as one course. The therapeutic efficacy, body weight and body mass index (BMI) were then observed and compared. Results: The total effective rate in the warm needling moxibustion group was 85.7% versus 77.1% in the EA group, and the between-group difference was statistically significant (P<0.05). The warm needling moxibustion was remarkably superior to the EA in weight loss and lowering BMI, both with statistical significance (P<0.05, P<0.01). At the three-month follow-up, the body weight and BMI further decreased in the warm needling moxibustion group (both P<0.05), and the levels were lower than those in the EA group (P<0.05, P<0.01). Conclusion: Warm needling moxibustion can produce reliable and consistent efficacy in the treatment of simple obesity due to yang deficiency of the spleen and kidney. Compared with EA, warm needling moxibustion shows advantage in both short-term and long-term efficacies, and thus is worth promotion in clinical practice.
10.Expression Level and Clinical Significance of VEGF, IL-17, β2-MG and IL-35 in Patients with Multiple Myeloma.
Xiao-Na JIN ; Bao-Zhen ZHOU ; Dang-Feng ZHANG
Journal of Experimental Hematology 2018;26(1):192-196
OBJECTIVETo explore the expression and clinical significance of VEGF, IL-17, β2-MG and IL-35 in patients with multiple myeloma.
METHODSA total of 83 patients with multiple myeloma (MM) from January 2012 to December 2016 were enrolled in MM group, 36 healthy subjects were enrolled in control group. The levels of IL-17, IL-35 and VEGF in serum were detected by ELISA. The levels of β2-MG in serum were measured by radioimmunoassay. The differences of different indexes between 2 groups were compared.
RESULTSThe serum levels of IL-17, VEGF and β2-MG in serum of III stage were higher than that in II stage, which was higher than that in I stage and control group (P<0.05). The levels of IL-35 in the control group were significantly higher than those in the I,II,III stage group (P<0.05). The levels of IL-17, VEGF and β2-MG in serum of progress period were higher than those in stable phase and control group, level of IL-35 in serum of control group was significantly higher than that in the stable phase and progress period group (P<0.05). The correlation analysis showed that the level of serum IL-17 positively correlated with VEGF, β2-MG expression (r=0.65, 0.58, P<0.05); and the serum IL-17 levels were negatively correlated with IL-35 levels (r=-0.42, P<0.05).
CONCLUSIONThe anomalous levels of IL-17, IL-35, IVEGF and β2-MG expressions correlate with the progression and prognosis of patients with multiple myeloma.

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