1.Mechanism analysis of fisetin regulating LKB1-AMPK-mTOR-p70S6K pathway to improve oligonasthenospermia in rats
Li-Bang CHEN ; Bing-Xiang SHEN ; Chun-Yuan HE ; Wei-Chen ZHAO ; Wei CHANG ; Tong-Sheng WANG
Chinese Pharmacological Bulletin 2024;40(7):1296-1301
Aim To investigate the protective effect of fisetin on testis and sperm of rats with oligoasthenosper-mia and to explore its mechanism.Methods The rat model of oligoasthenospermia was established.The rats were randomly divided into the blank group,model group,low-,medium-,and high-dose fisetin treat-ment groups,and LKB1 agonist group,with 10 rats in each group.ELISA was used to detect the levels of FSH,LH,T,E2 and PRL.Flow cytometry was used to detect sperm cell apoptosis.HE staining was used to detect testicular tissue damage.Transmission electron microscopy was used to detect the ultrastructure of sperm cells.qRT-PCR and Western blot were used to detect the mRNA and protein expression of LKB1,AMPK,mTOR,and p70S6K.Results Compared with the blank group,the levels of FSH,LH,PRL,T and other hormones in the model group and LKB1 ago-nist group were significantly reduced,and sperm cell apoptosis and testicular injury were severe.The ex-pressions of LKB1 and p-AMPK/AMPK were signifi-cantly up-regulated,while the expressions of mTOR and p-p70S6K/p70S6K were significantly down-regula-ted(P<0.05).Compared with the model group,af-ter different doses of fisetin treatment,the number of apoptotic sperm cells was significantly reduced,the levels of FSH,LH,PRL,T and other hormones markedly increased,the expression of LKB1 and p-AMPK/AMPK was significantly down-regulated,and the expression of mTOR and p-p70S6K/p70S6K was evidently up-regulated(P<0.05).Conclusion Fi-setin is effective in the treatment of oligoasthenospermia rats,which may be related to LKB1-AMPK-mTOR-p70S6K signaling pathway.
2.The effect of physiotherapeutic scoliosis specific exercises on adolescent idiopathic scoliosis:a meta analysis
Ying CHANG ; Sheng HU ; Xianghu ZHAO
Chinese Journal of Spine and Spinal Cord 2024;34(6):602-609
Objectives:To evaluate with meta-analysis the clinical effects of physiotherapeutic scoliosis spe-cific exercises(PSSE)comparing with other conservative treatments in treating adolescent idiopathic scoliosis(AIS).Methods:PubMed,Web of Science,The Cochrane Library,WanFang Data and China National Knowl-edge Infrastructure(CNKI)were searched by computer from their establishments to July 2023.The randomized controlled trials(RCTs)of PSSE therapy(PSSE therapy group)and other conservative treatments(control group)in treating AIS were collected.Two researchers independently screened the literature,extracted data and assessed the risk of bias of the included studies.Meta analysis was performed using RevMan 5.4 software on the Cobb angle,angle of trunk rotation(ATR),and quality of life score of Scoliosis Research Society-22(SRS-22)scale reported in the included literature,and subgroup analysis was carried on according to Cobb angle and treat-ment duration.Results:A total of 14 studies were included,consisting of 16 RCTs(2 studies included 2 RCTs each),involving 944 AIS patients.The quality of the literature was of medium and high.Meta analysis results showed that,comparing with the control group,the PSSE therapy group was superior in reducing Cobb angle of AIS patients(MD=1.64;95%CI:2.78,0.50;P<0.05)and ATR(MD=1.45;95%CI:-2.58,-0.32;P<0.05),and improving the SRS-22 quality of life score(MD=0.25;95%CI:0.17,0.33;P<0.05).The results of subgroup analysis showed that for the AIS patients with duration of treatment ≤6 months(MD=-2.88;95%CI:-3.85,-1.91;P<0.05)and a Cobb angle<25° at enrollment(MD=-2.41;95%CI:-3.51,-1.30;P<0.05),the PSSE therapy group had a better effect with a smaller Cobb angle(P<0.05)than the control group.In terms of ATR improvement,for the patients with treatment duration ≤6 months(MD=2.63;95%CI:3.30,1.96;P<0.05),the PSSE therapy group had a lower ATR degree comparing with the control group(P<0.05).Conclusions:Comparing with other conservative treatments,PSSE therapy has advantages in improving the Cobb angle,re-ducing ATR and improving the quality of life in AIS patients,especially for mild scoliosis patients with Cobb angle<25°.PSSE therapy has a better therapeutic effect on reducing the Cobb angle and ATR more obvious-ly in AIS patients with duration of treatment ≤6 months.
3.Small molecule deoxynyboquinone triggers alkylation and ubiquitination of Keap1 at Cys489 on Kelch domain for Nrf2 activation and inflammatory therapy
Linghu KE-GANG ; Zhang TIAN ; Zhang GUANG-TAO ; Lv PENG ; Zhang WEN-JUN ; Zhao GUAN-DING ; Xiong SHI-HANG ; Ma QIU-SHUO ; Zhao MING-MING ; Chen MEIWAN ; Hu YUAN-JIA ; Zhang CHANG-SHENG ; Yu HUA
Journal of Pharmaceutical Analysis 2024;14(3):401-415
Activation of nuclear factor erythroid 2-related factor 2(Nrf2)by Kelch-like ECH-associated protein 1(Keap1)alkylation plays a central role in anti-inflammatory therapy.However,activators of Nrf2 through alkylation of Keap1-Kelch domain have not been identified.Deoxynyboquinone(DNQ)is a natural small molecule discovered from marine actinomycetes.The current study was designed to investigate the anti-inflammatory effects and molecular mechanisms of DNQ via alkylation of Keap1.DNQ exhibited signif-icant anti-inflammatory properties both in vitro and in vivo.The pharmacophore responsible for the anti-inflammatory properties of DNQ was determined to be the α,β-unsaturated amides moieties by a chemical reaction between DNQ and N-acetylcysteine.DNQ exerted anti-inflammatory effects through activation of Nrf2/ARE pathway.Keap1 was demonstrated to be the direct target of DNQ and bound with DNQ through conjugate addition reaction involving alkylation.The specific alkylation site of DNQ on Keap1 for Nrf2 activation was elucidated with a synthesized probe in conjunction with liquid chromatography-tandem mass spectrometry.DNQ triggered the ubiquitination and subsequent degra-dation of Keap1 by alkylation of the cysteine residue 489(Cys489)on Keap1-Kelch domain,ultimately enabling the activation of Nrf2.Our findings revealed that DNQ exhibited potent anti-inflammatory capacity through α,β-unsaturated amides moieties active group which specifically activated Nrf2 signal pathway via alkylation/ubiquitination of Keap1-Kelch domain,suggesting the potential values of targeting Cys489 on Keap1-Kelch domain by DNQ-like small molecules in inflammatory therapies.
4.Study on the application of different-length peripheral intravenous catheters in patients undergoing metabolic and bariatric surgery:a randomized clinical trial
Xiaohui YANG ; Chang LIU ; Weihua YU ; Jionghuang CHEN ; Wanting SHENG ; Xiuzhu CAO ; Xufen ZENG ; Xianghong JIN ; Linfang ZHAO
Chinese Journal of Nursing 2024;59(4):401-407
Objective To investigate the appropriate venous access for obese patients undergoing metabolic and bariatric surgery by comparing the clinical outcomes of different lengths of peripheral intravenous catheters.Methods Inpatients who underwent bariatric surgery in a tertiary hospital in Zhejiang from August 2022 to December 2022 were selected as the study population using a fixed-point continuous convenience sampling method.A stratified block randomisation method was used to divide the group into an experimental group 1(mini-midline catheters),an experimental group 2(midline catheters)and a control group(short peripheral intravenous catheters,Short PIVCs).The incidence of catheter-related complications,the rate of extubation due to complications,the duration of catheter retention,the time to first catheter-related complication were compared in the 3 groups.Results A total of 186 patients were included,with 62 patients in each group.The overall incidence of catheter-related complications in experimental group 1,experimental group 2,and control group were 25.81%,8.06%,and 58.06%.The extubation rates due to complications were 19.35%,4.84%,and 41.94%,and the duration of catheter retention was 7.00(6.00,7.00)d,7.00(6.00,7.00)d,6.00(3.00,6.25)d.The differences were statistically different(P<0.05)when comparing the 3 groups.Among them,the differences in the overall incidence of catheter-related complications and the rate of extubation due to complications were statistically significant when comparing experimental group 1 with the control group,experimental group 2 with the control group,and experimental group 1 with experimental group 2(P<0.017);the duration of catheter retention in both experimental group 1 and experimental group 2 were higher than it in the control group,and the differences were statistically different(P<0.017).Conclusion The complication rate of mini-midline catheters and midline catheters is lower than that of short ones,and the indwelling time is consistent with the perioperative period of metabolic and bariatric surgery,which is suitable for use in patients undergoing metabolic and bariatric surgery.
5.Application of"rotation-correction loop technique"in the retrieval of complex inferior vena cava filters
Jie HU ; Maolin QIAO ; Qinqin TIAN ; Heng WANG ; Sheng YAN ; Wenbo ZHAO ; Yongbin SHI ; Peilu SHI ; Miao XING ; Haifeng LI ; Haijiang JIN ; Ping WANG ; Wenkai CHANG ; Yuwen WANG ; Honglin DONG
Journal of Interventional Radiology 2024;33(3):289-294
Objective To discuss the application of the"rotating guidewire and correcting the filter recovery hook direction technique"("rotation-correction loop technique"for short),a technique invented by the authors in clinical practice,in the retrieval of complex inferior vena cava filter(IVCF),and to discuss its technical skills and advantages.Methods The clinical data of 417 patients carrying an IVCF,who were admitted to the Department of Vascular Surgery of Second Hospital of Shanxi Medical University of China to retrieve IVCF between January 2022 and December 2022,were retrospectively analyzed.Taking the time spent on the retrieval of IVCF and the intraoperative radiation dose as the evaluation indicators,the advantages and disadvantages of the standard filter retrieval technique,the"rotation-correction loop technique"and the other loop-assisted techniques were compared.Results Both the intraoperative radiation dose and the time spent on the retrieval of IVCF using"rotation-correction loop technique"were remarkably lower than those of other loop-assisted techniques(P<0.000 1).Conclusion For the retrieval of complex IVCF,especially for the IVCF which is heavily tilted and/or its recovered hook is attached to the vascular wall,the use of"rotation-correction loop technique"can shorten the time spent on the the retrieval of IVCF and reduce the intraoperative radiation dose.This technique carries high safety and practicability,the device is simple and it can be manipulated by single physician,which is conducive to clinical application and promotion.(J Intervent Radiol,2024,33:289-294)
6.The chemical constituents and hypoglycemic activity of alcoholic extract of sea buckthorn leaves
Chang-yu YAN ; Zhao-jun DING ; Xiao-min LI ; Xin-liang MAO ; Zong-sheng YU ; Zhi-fang WANG ; Jian-wen YE ; Kurihara HIROSHI ; Yi-fang LI ; Lei LIANG ; Rong-rong HE
Acta Pharmaceutica Sinica 2023;58(2):396-404
The purpose of this research is to identify the chemical constituents of sea buckthorn leaves extract (SBLE) and explore its hypoglycemic biological activity. SBLE was prepared by hot reflux extraction with 65% ethanol, and its chemical composition was analyzed by ultra-high-performance liquid chromatography-photodiode array-mass spectrometry/mass spectrometry (UHPLC-PDA-MS/MS) system. The animal experiments were compliant with ethical principles for animal use and had been approved by the Animal Experiment Ethics Committee of Jinan University. Mice were injected with streptozocin (STZ) to establish a hyperglycemic animal model, and SBLE (1.5 g·kg-1) was administered by gavage for 5 weeks. The fasting blood glucose (FBG) and oral glucose tolerance were detected. Normal mice were given SBLE (1.5 g·kg-1) by intragastric administration for 10 days, and blood was collected from the tail vein to detect the changes in blood glucose within 120 min after sucrose or starch loading. The mucous membrane of the small intestine of mice was taken to detect the activity of
7.The timing of pericardial drainage catheter removal and restart of the anticoagulation in patients suffered from perioperative pericardial tamponade during atrial fibrillation catheter ablation and uninterrupted dabigatran: Experiences from 20 cases.
Xin ZHAO ; Wen Li DAI ; Xin SU ; Jia Hui WU ; Chang Qi JIA ; Li FENG ; Man NING ; Yan Fei RUAN ; Song ZUO ; Rong HU ; Xin DU ; Jian Zeng DONG ; Chang Sheng MA
Chinese Journal of Cardiology 2023;51(1):45-50
Objective: To investigate the timing of pericardial drainage catheter removal and restart of the anticoagulation in patients with atrial fibrillation (AF) suffered from perioperative pericardial tamponade during atrial fibrillation catheter ablation and uninterrupted dabigatran. Methods: A total of 20 patients with pericardial tamponade, who underwent AF catheter ablation with uninterrupted dabigatran in Beijing Anzhen Hospital from January 2019 to August 2021, were included in this retrospective analysis. The clinical characteristics of enrolled patients, information of catheter ablation procedures, pericardial tamponade management, perioperative complications, the timing of pericardial drainage catheter removal and restart of anticoagulation were analyzed. Results: All patients underwent pericardiocentesis and pericardial effusion drainage was successful in all patients. The average drainage volume was (427.8±527.4) ml. Seven cases were treated with idarucizumab, of which 1 patient received surgical repair. The average timing of pericardial drainage catheter removal and restart of anticoagulation in 19 patients without surgical repair was (1.4±0.7) and (0.8±0.4) days, respectively. No new bleeding, embolism and death were reported during hospitalization and within 30 days following hospital discharge. Time of removal of pericardial drainage catheter, restart of anticoagulation and hospital stay were similar between patients treated with idarucizumab or not. Conclusion: It is safe and reasonable to remove pericardial drainage catheter and restart anticoagulation as soon as possible during catheter ablation of atrial fibrillation with uninterrupted dabigatran independent of the idarucizumab use or not in case of confirmed hemostasis.
Humans
;
Atrial Fibrillation/drug therapy*
;
Dabigatran/therapeutic use*
;
Cardiac Tamponade/complications*
;
Anticoagulants/therapeutic use*
;
Retrospective Studies
;
Treatment Outcome
;
Drainage/adverse effects*
;
Catheter Ablation
;
Catheters/adverse effects*
9.A prospective study on application of human umbilical cord mesenchymal stem cells combined with autologous Meek microskin transplantation in patients with extensive burns.
Tian Tian YAN ; Rong XIAO ; Ying WANG ; Guo An LIN ; Yin ZHENG ; Hui ZHAO ; Wen Jun LI ; Xin Zhi SHANG ; Jin Song MENG ; Dong Sheng HU ; Song LI ; Chao WANG ; Zhi Chen LIN ; Hong Chang CHEN ; Dong Yan ZHAO ; Di TANG
Chinese Journal of Burns 2023;39(2):114-121
Objective: To investigate the effects of human umbilical cord mesenchymal stem cells (hUCMSCs) combined with autologous Meek microskin transplantation on patients with extensive burns. Methods: The prospective self-controlled study was conducted. From May 2019 to June 2022, 16 patients with extensive burns admitted to the 990th Hospital of PLA Joint Logistics Support Force met the inclusion criteria, while 3 patients were excluded according to the exclusion criteria, and 13 patients were finally selected, including 10 males and 3 females, aged 24-61 (42±13) years. A total of 20 trial areas (40 wounds, with area of 10 cm×10 cm in each wound) were selected. Two adjacent wounds in each trial area were divided into hUCMSC+gel group applied with hyaluronic acid gel containing hUCMSCs and gel only group applied with hyaluronic acid gel only according to the random number table, with 20 wounds in each group. Afterwards the wounds in two groups were transplanted with autologous Meek microskin grafts with an extension ratio of 1∶6. In 2, 3, and 4 weeks post operation, the wound healing was observed, the wound healing rate was calculated, and the wound healing time was recorded. The specimen of wound secretion was collected for microorganism culture if there was purulent secretion on the wound post operation. In 3, 6, and 12 months post operation, the scar hyperplasia in wound was assessed using the Vancouver scar scale (VSS). In 3 months post operation, the wound tissue was collected for hematoxylin-eosin (HE) staining to observe the morphological changes and for immunohistochemical staining to observe the positive expressions of Ki67 and vimentin and to count the number of positive cells. Data were statistically analyzed with paired samples t test and Bonferronni correction. Results: In 2, 3, and 4 weeks post operation, the wound healing rates in hUCMSC+gel group were (80±11)%, (84±12)%, and (92±9)%, respectively, which were significantly higher than (67±18)%, (74±21)%, and (84±16)% in gel only group (with t values of 4.01, 3.52, and 3.66, respectively, P<0.05). The wound healing time in hUCMSC+gel group was (31±11) d, which was significantly shorter than (36±13) d in gel only group (t=-3.68, P<0.05). The microbiological culture of the postoperative wound secretion specimens from the adjacent wounds in 2 groups was identical, with negative results in 4 trial areas and positive results in 16 trial areas. In 3, 6, and 12 months post operation, the VSS scores of wounds in gel only group were 7.8±1.9, 6.7±2.1, and 5.4±1.6, which were significantly higher than 6.8±1.8, 5.6±1.6, and 4.0±1.4 in hUCMSC+gel group, respectively (with t values of -4.79, -4.37, and -5.47, respectively, P<0.05). In 3 months post operation, HE staining showed an increase in epidermal layer thickness and epidermal crest in wound in hUCMSC+gel group compared with those in gel only group, and immunohistochemical staining showed a significant increase in the number of Ki67 positive cells in wound in hUCMSC+gel group compared with those in gel only group (t=4.39, P<0.05), with no statistically significant difference in the number of vimentin positive cells in wound between the 2 groups (P>0.05). Conclusions: The application of hyaluronic acid gel containing hUCMSCs to the wound is simple to perform and is therefore a preferable route. Topical application of hUCMSCs can promote healing of the autologous Meek microskin grafted area in patients with extensive burns, shorten wound healing time, and alleviate scar hyperplasia. The above effects may be related to the increased epidermal thickness and epidermal crest, and active cell proliferation.
Female
;
Humans
;
Male
;
Burns/surgery*
;
Cicatrix
;
Eosine Yellowish-(YS)
;
Hyaluronic Acid/therapeutic use*
;
Hyperplasia
;
Ki-67 Antigen
;
Prospective Studies
;
Umbilical Cord
;
Vimentin
;
Young Adult
;
Adult
;
Middle Aged
10.Taste masking pharmaceutical excipients and their applications
Xiang-an-ni KONG ; Lei ZHAO ; Wen-zhen ZHAN ; Yu-xuan LI ; Chang LI ; Jia-sheng TU ; Chun-meng SUN
Acta Pharmaceutica Sinica 2023;58(11):3179-3184
The taste of drugs has an important impact on the compliance of patients, but most of the active drug ingredients have an uncomfortable taste, especially traditional Chinese medicine. Through a variety of pharmaceutical excipients with taste masking properties combined with corresponding technologies can improve the taste of drugs and the characteristics of other dosage forms, so as to improve patient compliance. Here, we mainly summarize the auxiliary materials used for taste masking, explain the mechanism of taste masking from the point of view of excipients and introduces related uses, so as to provide reference for further research on taste masking of pediatric preparations.

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