1.SIRT6 as a key event linking P53 and NRF2 counteracts APAP-induced hepatotoxicity through inhibiting oxidative stress and promoting hepatocyte proliferation.
Yanying ZHOU ; Xiaomei FAN ; Tingying JIAO ; Wenzhou LI ; Panpan CHEN ; Yiming JIANG ; Jiahong SUN ; Yixin CHEN ; Pan CHEN ; Lihuan GUAN ; Yajie WEN ; Min HUANG ; Huichang BI
Acta Pharmaceutica Sinica B 2021;11(1):89-99
Acetaminophen (APAP) overdose is the leading cause of drug-induced liver injury, and its prognosis depends on the balance between hepatocyte death and regeneration. Sirtuin 6 (SIRT6) has been reported to protect against oxidative stress-associated DNA damage. But whether SIRT6 regulates APAP-induced hepatotoxicity remains unclear. In this study, the protein expression of nuclear and total SIRT6 was up-regulated in mice liver at 6 and 48 h following APAP treatment, respectively.
2.Neoadjuvant Chemotherapy–Guided Bladder-Sparing Treatment for Muscle-Invasive Bladder Cancer: Results of a Pilot Phase II Study
Hongzhe SHI ; Wen ZHANG ; Xingang BI ; Dong WANG ; Zejun XIAO ; Youyan GUAN ; Kaopeng GUAN ; Jun TIAN ; Hongsong BAI ; Linjun HU ; Chuanzhen CAO ; Weixing JIANG ; Zhilong HU ; Jin ZHANG ; Yan CHEN ; Shan ZHENG ; Xiaoli FENG ; Changling LI ; Yexiong LI ; Jianhui MA ; Yueping LIU ; Aiping ZHOU ; Jianzhong SHOU
Cancer Research and Treatment 2021;53(4):1156-1165
Purpose:
Reduced quality of life after cystectomy has made bladder preservation a popular research topic for muscle-invasive bladder cancer (MIBC). Previous research has indicated significant tumor downstaging after neoadjuvant chemotherapy (NAC). However, maximal transurethral resection of bladder tumor (TURBT) was performed before NAC to define the pathology, impacting the real evaluation of NAC. This research aimed to assess real NAC efficacy without interference from TURBT and apply combined modality therapies guided by NAC efficacy.
Materials and Methods:
Patients with cT2-4aN0M0 MIBC were confirmed by cystoscopic biopsy and imaging. NAC efficacy was assessed by imaging, urine cytology, and cystoscopy with multidisciplinary team discussion. Definite responders (≤ T1) underwent TURBT plus concurrent chemoradiotherapy. Incomplete responders underwent radical cystectomy or partial cystectomy if feasible. The primary endpoint was the bladder preservation rate.
Results:
Fifty-nine patients were enrolled, and the median age was 63 years. Patients with cT3-4 accounted for 75%. The median number of NAC cycles was three. Definite responders were 52.5%. The complete response (CR) was 10.2%, and 59.3% of patients received bladder-sparing treatments. With a median follow-up of 44.6 months, the 3-year overall survival (OS) was 72.8%. Three-year OS and relapse-free survival were 88.4% and 60.0% in the bladder-sparing group but only 74.3% and 37.5% in the cystectomy group. The evaluations of preserved bladder function were satisfactory.
Conclusion
After stratifying MIBC patients by NAC efficacy, definite responders achieved a satisfactory bladder-sparing rate, prognosis, and bladder function. The CR rate reflected the real NAC efficacy for MIBC. This therapy is worth verifying through multicenter research.
3.Effect of dexmedetomidine hydrochloride on inflammatory response induced by lipopolysaccharide in Kupffer cells
Hui LIN ; Dong-Huan WU ; Guan-Wen LIN ; Bi-Shan OUYANG
The Chinese Journal of Clinical Pharmacology 2019;35(7):667-670
Objective To study the effect of dexmedetomidine hydrochloride (Dex) on lipopolysaccharide (LPS) induced inflammatory response in Kupffer cells. Methods Healthy male SD rats were selected for isolation and culture of liver Kupffer cells. The cells were randomly divided into 6 groups: normal group, model group, experimental-L group, experimental-H group, combined group and control group. The normal group was cultured routinely, model group was cultured with 1μg·m L-1 LPS solution 3 h, experimental-L, experimental-H group were cultured respectively with 0. 01 μmol·L-1 or 1 μmol·L-1 Dex 24 h + 1 μg·m L-1 LPS solution 3 h, combined group was cultured with 1μmol·L-1 Dex + 100 μmol·L-1 yohimbine hydrochloride (α2 adrenergicreceptor antagonist) 24 h + 1 μg·m L-1 LPS 3 h, control group was cultured with 100 μmol·L-1 yohimbine hydrochloride 24 h. The survival rate of Kupffer cells was determined by MTT. The contents of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the supernatant of Kupffer cells were determined by enzyme linked immunosorbent assay. Results After disposal, the survival rates of Kupffer cells in normal group, model group, experimental-L group, experimental-H group, combined group and control group were respectively (100. 00 ± 0. 00) %, (56. 35 ± 4. 21) %, (64. 78 ± 4. 37) %, (83. 84 ± 5. 16) %, (57. 03 ± 4. 09) % and (54. 58 ± 3. 95) %. The TNF-αin the 6 groups were respectively (1. 19 ± 0. 16) , (57. 36 ± 7. 23) , (48. 27 ± 5. 58) , (7. 64 ± 0. 92) , (56. 98 ± 7. 05) and (58. 03 ± 7. 34) ng ·m L-1; the IL-6 in the 6 groups were respectively (47. 38 ± 6. 05) , (289. 49 ± 27. 83) , (231. 17 ± 22. 58) , (85. 35 ± 8. 23) , (287. 96 ± 26. 45) and (291. 43 ± 28. 04) pg·m L-1. Comparison between model group and normal group, the differences of the factors were significant (all P < 0. 05) ; comparison between two dose experimental groups and model group, the differences of the factors were significant (all P < 0. 05) ; comparison between combined group and control group with two dose experimental groups, the differences of the factors were significant (all P < 0. 05) . Conclusion Dex can reduce the activity of LPS induced Kupffer cells in a dose-dependent manner, inhibit oxidative stress injury and inflammatory response induced by Kupffer cells, which may be related to the agitation ofα2 adrenalic receptor. Yohimbine has antagonistic effect on its therapeutic effect.
4.Treatment of Sanders II calcaneus fractures via minimally invasive sinus tarsi approach.
Xue-Xun BAO ; Chen-Jie XIA ; Bi-Yun ZHAO ; De-Jun SHI ; Guan-Hua LAN ; Guo-Lin REN ; Zu-Hong XIE ; Wen-Xi DU
China Journal of Orthopaedics and Traumatology 2017;30(8):755-758
OBJECTIVETo study the feasibility and clinical efficacy of a minimally invasive sinus tarsi approach in the treatment of Sanders II calcaneus fractures.
METHODSFrom August of 2015 to July of 2016, 13 patients(totally 13 feet) with Sanders II intra-articular calcaneus fractures were treated via the minimally invasive sinus tarsi approach. The Böhler angle, Gissane angle and the length, width and height of calcaneus were compared between pre-operation and post-operation. The AOFAS ankle and foot scoring system of the orthopaedic ankle foot Association was used to evaluate the efficacy.
RESULTSAll the patients were followed up, and the duration ranged from 6 to 15 months, with an average of 9.5 months. No incision complications occurred. The Böhler angle was increased from preoperative (18.82±5.11)° to postoperative(26.63±4.45)°(=-4.16,=0.000). The Gissane angle was increased from preoperative(111.07±15.36)° to postoperative (124.56±8.71)° (=-2.75,=0.011). The length, width, height of calcaneus were absolutely improved from preoperative(69.82±5.95) mm, (42.07±3.68) mm, (41.20±3.90) mm to preoperatively(72.61±5.46) mm, (39.10±4.02) mm, (44.03±3.33) mm. According to the AOFAS, 8 patients got an excellent result, 4 good and 1 poor, and the postoperative mean score was 88.2±5.9.
CONCLUSIONSThe limited open sinus tarsi approach could be used successfully to treat displaced Sanders II fractures with less injury and effectively restored the surface of subtalar joint, however the method is not fit for the patients with comminuted fracture in lateral wall and great change in the length, width, height, varus and valgus of calcaneus.
5.Toxicity of multi-walled carbon nanotubes, graphene oxide, and reduced graphene oxide to zebrafish embryos.
Xiao Tong LIU ; Xi Yan MU ; Xiao Li WU ; Li Xuan MENG ; Wen Bi GUAN ; Yong Qiang MA ; Hua SUN ; Cheng Ju WANG ; Xue Feng LI
Biomedical and Environmental Sciences 2014;27(9):676-683
OBJECTIVEThis study was aimed to investigate the toxic effects of 3 nanomaterials, i.e. multi-walled carbon nanotubes (MWCNTs), graphene oxide (GO), and reduced graphene oxide (RGO), on zebrafish embryos.
METHODSThe 2-h post-fertilization (hpf) zebrafish embryos were exposed to MWCNTs, GO, and RGO at different concentrations (1, 5, 10, 50, 100 mg/L) for 96 h. Afterwards, the effects of the 3 nanomateria on spontaneous movement, heart rate, hatching rate, length of larvae, mortality, and malformations ls were evaluated.
RESULTSStatistical analysis indicated that RGO significantly inhibited the hatching of zebrafish embryos. Furthermore, RGO and MWCNTs decreased the length of the hatched larvae at 96 hpf. No obvious morphological malformation or mortality was observed in the zebrafish embryos after exposure to the three nanomaterials.
CONCLUSIONMWCNTs, GO, and RGO were all toxic to zebrafish embryos to influence embryos hatching and larvae length. Although no obvious morphological malformation and mortality were observed in exposed zebrafish embryos, further studies on the toxicity of the three nanomaterials are still needed.
Animals ; Embryo, Nonmammalian ; Embryonic Development ; drug effects ; Female ; Graphite ; toxicity ; Heart Rate ; drug effects ; Male ; Movement ; drug effects ; Nanotubes, Carbon ; toxicity ; Oxides ; toxicity ; Toxicity Tests ; Zebrafish
6.Prenatal sonographic ifndings of urorectal septum malformation sequence in female
Ying, YUAN ; Shengli, LI ; Huaxuan, WEN ; Jingru, BI ; Qiong, ZHENG ; Rong, YU ; Yong, GUAN
Chinese Journal of Medical Ultrasound (Electronic Edition) 2014;(9):737-742
Objective To summarize and analyze prenatal ultrasound and postnatal autopsy ifndings in fetuses with urorectal septum malformation sequence (URSMS). Methods An analysis of prenatal ultrsound ifndings and postnatal autopsy features was performed on eleven cases of fetuses with URSMS that were identiifed by ultrasonography at Shenzhen Maternity&Child Healthcare Hospital in the period of January 2003 to December 2012. Results Prenatal ultrasonography showed a large abdominal cystic mass concomitant with imperforate anus in eleven fetuses with URSMS. The cyst contained unilocular or bilocular cystic structures in two fetuses, and trilocular cystic structures in nine fetuses. The cyst was demonstrated as clear acoustic transmission in three fetuses and unclear in eight fetuses. Out of them, seven fetuses had kidney abnormalities, six had ascites, and three had enterolithiasis. The associated systemic abnormalities included tethered cord in two fetuses, single umbilical artery in two fetuses, sacrococcygeal dysplasia in one fetus, and myocardial noncompaction in one fetus. 21-trisomy was found in one fetus by chromosome examination. Eleven cases were all identiifed as female fetuses by autopsy ifndings, including a single perineal opening and ambiguous genitalia with clitoral hypertrophy and labial fusion. The internal genital abnormalities included double vagina or longitudinal vaginal septum in nine fetuses, double uterus or uterus bicornis in ten fetuses and vaginal dysplasia in one fetus. Conclusions URSMS is a complex congenital malformation, which includes abnormalities of the urinary system, reproductive system and gastrointestinal track. An abdominal cystic mass visualized by prenatal ultrasonography might be the distinctive lesion in female with URSMS, and have an important diagnostic value. The kidney abnormalities and ambiguous genitalia can contribute to the diagnosis of URSMS.
7.Value of postoperative adjuvant chemotherapy in locally advanced rectal cancer patients with ypT1-4N0 after neo-adjuvant chemoradiotherapy.
Kai-yun YOU ; Hai-hua PENG ; Yuan-hong GAO ; Li CHEN ; Guan-qun ZHOU ; Hui CHANG ; Xiao-jing DU ; Lin XIAO ; Zhi-fan ZENG ; Bi-xiu WEN ; Meng-zhong LIU
Chinese Journal of Oncology 2013;35(9):708-713
OBJECTIVEThe purpose of this study was to investigate the value of postoperative chemotherapy for locally advanced rectal cancer patients who reached pathological ypT1-4N0 after neo-adjuvant chemoradiotherapy.
METHODSWe performed a retrospective study of 104 patients treated with preoperative chemoradiotherapy followed by radical resection, who achieved pathological ypT1-4N0, between Mar 2003 and Dec 2010. There were 73 patients who received postoperative adjuvant chemotherapy, and the other 31 patients did not. The distribution of final pathologic stages for these patients was ypT1-2N0 in 39 cases and ypT3-4N0 in 65 cases.
RESULTSThe median follow-up was 41 months. The 3-year overall survival rate (OS) and recurrence-free survival rate (RFS) for the whole group (ypT1-4N0) were 93.4% and 85.3%, respectively. The 3-year OS and RFS in the adjuvant chemotherapy group and non-adjuvant chemotherapy group were 95.5%, 88.6% and 88.6%, 77.2%, respectively. There were no significant differences in 3-year RFS (P = 0.108) and OS (P = 0.106) between the two groups. The 3-year local recurrence and distant metastasis rates in the adjuvant chemotherapy group were 4.1% (3/73) and 5.5% (4/73), while for the non-adjuvant chemotherapy group, the 3-year local recurrence rate and distant metastasis rate were 3.2% (1/31) and 16.1% (5/31), respectively. Significant difference was found in distant metastasis rates (P = 0.030) between the two groups, but not in local recurrence rates (P = 0.676).Further subgroup analysis indicated that for the ypT1-2N0 patients, there were no significant differences in 3-year OS (P = 0.296) and RFS (P = 0.939) between the adjuvant and non-adjuvant chemotherapy groups, while negative results displayed in 3-year local recurrence rates (P = 0.676) and distant metastasis rates (P = 0.414). However, for patients with ypT3-4N0, significant differences were showed in both the 3-year OS (P = 0.034) and RFS (P = 0.025), and further analysis revealed that the 3-year distant metastasis rate was significantly higher in the non-adjuvant chemotherapy group than in the adjuvant chemotherapy group (P = 0.010) , but with non-significant difference in the 3-year local recurrence (P = 0.548).
CONCLUSIONSAdjuvant chemotherapy may not improve survival for ypT1-2N0 patients. However, it may be clinically meaningful for ypT3-4N0 patients by decreasing distant metastasis rate. Further randomized controlled clinical trials are needed to confirm our results.
Adenocarcinoma ; drug therapy ; pathology ; radiotherapy ; surgery ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Chemoradiotherapy, Adjuvant ; Chemotherapy, Adjuvant ; Deoxycytidine ; analogs & derivatives ; therapeutic use ; Female ; Fluorouracil ; analogs & derivatives ; therapeutic use ; Follow-Up Studies ; Humans ; Leucovorin ; therapeutic use ; Male ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Organoplatinum Compounds ; therapeutic use ; Postoperative Period ; Radiotherapy, Conformal ; Rectal Neoplasms ; drug therapy ; pathology ; radiotherapy ; surgery ; Retrospective Studies ; Survival Rate ; Young Adult
8.Prevalence, awareness, treatment, and control of hypertension in the non-dialysis chronic kidney disease patients.
Ying ZHENG ; Guang-Yan CAI ; Xiang-Mei CHEN ; Ping FU ; Jiang-Hua CHEN ; Xiao-Qiang DING ; Xue-Qing YU ; Hong-Li LIN ; Jian LIU ; Ru-Juan XIE ; Li-Ning WANG ; Zhao-Hui NI ; Fu-You LIU ; Ai-Ping YIN ; Chang-Ying XING ; Li WANG ; Wei SHI ; Jian-She LIU ; Ya-Ni HE ; Guo-Hua DING ; Wen-Ge LI ; Guang-Li WU ; Li-Ning MIAO ; Nan CHEN ; Zhen SU ; Chang-Lin MEI ; Jiu-Yang ZHAO ; Yong GU ; Yun-Kai BAI ; Hui-Min LUO ; Shan LIN ; Meng-Hua CHEN ; Li GONG ; Yi-Bin YANG ; Xiao-Ping YANG ; Ying LI ; Jian-Xin WAN ; Nian-Song WANG ; Hai-Ying LI ; Chun-Sheng XI ; Li HAO ; Yan XU ; Jing-Ai FANG ; Bi-Cheng LIU ; Rong-Shan LI ; Rong WANG ; Jing-Hong ZHANG ; Jian-Qin WANG ; Tan-Qi LOU ; Feng-Min SHAO ; Feng MEI ; Zhi-Hong LIU ; Wei-Jie YUAN ; Shi-Ren SUN ; Ling ZHANG ; Chun-Hua ZHOU ; Qin-Kai CHEN ; Shun-Lian JIA ; Zhi-Feng GONG ; Guang-Ju GUAN ; Tian XIA ; Liang-Bao ZHONG ; null
Chinese Medical Journal 2013;126(12):2276-2280
BACKGROUNDData on the epidemiology of hypertension in Chinese non-dialysis chronic kidney disease (CKD) patients are limited. The aim of the present study was to investigate the prevalence, awareness, treatment, and control of hypertension in the non-dialysis CKD patients through a nationwide, multicenter study in China.
METHODSThe survey was performed in 61 tertiary hospitals in 31 provinces, municipalities, and autonomous regions in China (except Hong Kong, Macao, and Taiwan). Trained physicians collected demographic and clinical data and measured blood pressure (BP) using a standardized protocol. Hypertension was defined as systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg, and/or use of antihypertensive medications. BP < 140/90 mmHg and < 130/80 mmHg were used as the 2 thresholds of hypertension control. In multivariate logistic regression with adjustment for sex and age, we analyzed the association between CKD stages and uncontrolled hypertension in non-dialysis CKD patients.
RESULTSThe analysis included 8927 non-dialysis CKD patients. The prevalence, awareness, and treatment of hypertension in non-dialysis CKD patients were 67.3%, 85.8%, and 81.0%, respectively. Of hypertensive CKD patients, 33.1% and 14.1% had controlled BP to < 140/90 mmHg and < 130/80 mmHg, respectively. With successive CKD stages, the prevalence of hypertension in non-dialysis CKD patients increased, but the control of hypertension decreased (P < 0.001). When the threshold of BP < 130/80 mmHg was considered, the risk of uncontrolled hypertension in CKD 2, 3a, 3b, 4, and 5 stages increased 1.3, 1.4, 1.4, 2.5, and 4.0 times compared with CKD 1 stage, respectively (P < 0.05). Using the threshold of < 140/90 mmHg, the risk of uncontrolled hypertension increased in advanced stages (P < 0.05).
CONCLUSIONSThe prevalence of hypertension Chinese non-dialysis CKD patients was high, and the hypertension control was suboptimal. With successive CKD stages, the risk of uncontrolled hypertension increased.
Adult ; Aged ; Awareness ; Female ; Humans ; Hypertension ; complications ; epidemiology ; therapy ; Male ; Middle Aged ; Prevalence ; Renal Insufficiency, Chronic ; complications
9.Clinical application of ultrasound three perpendicular planes plus special planes in diagnosis of fetal cleft lip/palate
Xiu-lan, CHEN ; Sheng-li, LI ; Jing-ru, BI ; Yuan, YAO ; Zhi-lian, XIAO ; Yu-rong OUYANG ; Cong-ying, CHEN ; YUAN-YING ; GUAN, YONG ; Rong, YU ; xuan Hua, WEN ; Hui-wen, LIU ; Ren-kun ZHUANG ; Qin-kai, ZENG ; Yuan-yuan, FANG ; Qiong, ZHENG
Chinese Journal of Medical Ultrasound (Electronic Edition) 2013;(7):542-547
Objective To study the clinical significance of the method of three perpendicular planes plus special planes in diagnosing fetal cleft lip /palate by prenatal ultrasound .Methods The approach of three perpendicular planes and special planes were used in diagnosing 110 cases of cleft lip/palate.The sonogram features in each section were analyzed and the outcomes were recorded during follow-up.Results On prenatal ultrsound ,110 cases were examined with three perpendicular planes method .The coronary section could be displayed at 100%cases (110 cases), sagittal section 76.4%cases (84 cases),transverse section 96.4%cases (106 cases) and parasagittal section 25.5%cases (28 cases).With special planes method,74 cases were examined .The section through pyriform aperture could be displayed in 47 cases,in 45 cases on the section through the lower lip/lower jaw/submandibular triangle ,and in 16 cases on the section through the cheek.Combining the three perpendicular planes and special planes methods ,94.5%(104/110) cases could be diagnosed definitely.Six cases (5.5%,6/110) were missed because of fetal position or oligoamnios . Conclusions The method of three perpendicular planes plus special planes is effective in prenatal ultrasound diagnosing cleft lip/palate,which is of great help in improving prenatal diagnostic accuracy of fetal cleft lip/palate.
10.Etiologic detection and epidemiological analysis of one suspected case of diphtheria in Guangdong province.
Mei-zhen LIU ; Wei-zheng ZHANG ; Jun SHU ; Jing-diao CHEN ; Da-wei GUAN ; Chuan-xi FU ; Bo YANG ; Bi-xia KE ; Chang-wen KE
Chinese Journal of Preventive Medicine 2011;45(10):909-911
OBJECTIVETo clarify the diagnosis of one suspected case of diphtheria in Guangdong province by epidemiological analysis and etiologic detection.
METHODSOn July 6th 2010, the corynebacterium diphtheria was detected from the nasal secretions of one nasopharyngeal carcinoma patient in a college-town hospital in Guangzhou City, Guangdong Province. The patient and the close contacts were asked to participate in the epidemiological survey; and their nasopharyngeal swabs (3 samples) and the nasal secretions of the patient (1 sample) were collected. The bacteria of the samples were isolated and cultured by blood plate and agar loefflera. The smears of positive strains were dyed and identified by BioMerieux API Coryne biochemical card. Gene tox of β-Corynebacteriophage, Corynebacterium diphtheriae was tested by PCR method, the aliphatic acid was analyzed by gas chromatography method and the Corynebacterium diphtheriae (CMCC 38009) was selected as positive control.
RESULTSThe patient had not gone out, neither had been visited. The patient denied history of vaccines or the immunizations. From the survey on patient's family members and close contacts, no similar symptoms had been found. One strain of Corynebacterium diphtheriae was isolated from the patient's nasal secretions, Gram positive and shape diversified. After cultured by agar loefflera and Gram-dyed and Neisser-dyed, one end or both two ends of the strain showed typical metachromatic granule. API Coryne was identified to Corynebacterium diphtheriae mitis/belfanti (99.4%). The result of gas chromatography method also indicated Corynebacterium diphtheriae. No Corynebacterium diphtheriae was isolated from the nasopharyngeal swabs, neither of the patient nor of the close contacts. The gene tox of β-Corynebacteriophage, Corynebacterium diphtheriae was negative according to the PCR test.
CONCLUSIONThe isolated Corynebacterium diphtheriae did not produce toxin as there was no biological structure gene of toxin. The patient was a health carrier of nontoxic Corynebacterium diphtheriae.
China ; epidemiology ; Corynebacterium diphtheriae ; isolation & purification ; Diphtheria ; epidemiology ; microbiology ; Female ; Humans ; Middle Aged ; Nasopharynx ; microbiology ; Polymerase Chain Reaction ; methods

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