1.Hepatic protein phosphatase 1 regulatory subunit 3G alleviates obesity and liver steatosis by regulating the gut microbiota and bile acid metabolism
Zhang CHU ; Wang GUI ; Yin XIN ; Gou LINGSHAN ; Guo MENGYUAN ; Suo FENG ; Zhuang TAO ; Yuan ZHENYA ; Liu YANAN ; Gu MAOSHENG ; Yao RUIQIN
Journal of Pharmaceutical Analysis 2024;14(8):1222-1237
Intestinal dysbiosis and disrupted bile acid(BA)homeostasis are associated with obesity,but the precise mechanisms remain insufficiently explored.Hepatic protein phosphatase 1 regulatory subunit 3G(PPP1R3G)plays a pivotal role in regulating glycolipid metabolism;nevertheless,its obesity-combatting potency remains unclear.In this study,a substantial reduction was observed in serum PPP1R3G levels in high-body mass index(BMI)and high-fat diet(HFD)-exposed mice,establishing a positive correlation between PPP1R3G and non-12α-hydroxylated(non-12-OH)BA content.Additionally,hepatocyte-specific overexpression of Ppp1r3g(PPP1R3G HOE)mitigated HFD-induced obesity as evidenced by reduced weight,fat mass,and an improved serum lipid profile;hepatic steatosis alleviation was confirmed by normalized liver enzymes and histology.PPP1R3G HOE considerably impacted systemic BA homeostasis,which notably increased the non-12-OH BAs ratio,particularly lithocholic acid(LCA).16S ribosomal DNA(16S rDNA)sequencing assay indicated that PPP1R3G HOE reversed HFD-induced gut dysbiosis by reducing the Firmicutes/Bacteroidetes ratio and Lactobacillus population,and elevating the relative abundance of Blautia,which exhibited a positive correlation with serum LCA levels.A fecal microbiome transplantation test confirmed that the anti-obesity effect of hepatic PPP1R3G was gut microbiota-dependent.Mechanistically,PPP1R3G HOE markedly suppressed hepatic cholesterol 7α-hydroxylase(CYP7A1)and sterol-12α-hydroxylase(CYP8B1),and concurrently upregulated oxysterol 7-α hydroxylase and Takeda G protein-coupled BA receptor 5(TGR5)expression under HFD conditions.Furthermore,LCA administration significantly mitigated the HFD-induced obesity phenotype and elevated non-12-OH BA levels.These findings emphasize the significance of hepatic PPP1R3G in ameliorating diet-induced adiposity and hepatic steatosis through the gut microbiota-BA axis,which may serve as potential ther-apeutic targets for obesity-related disorders.
2.Implementation of teaching clinic in the standardized training of general practice residents: current situation and implications
Xinyan YU ; Lingyan WU ; Lingna MAO ; Ming NI ; Zhizhi JIANG ; Yuling TONG ; Yi GUO ; Zhenya SONG ; Zhijie XU
Chinese Journal of Medical Education Research 2024;23(9):1281-1285
Teaching clinics represent a unique form of outpatient training of resident physicians and serve as a crucial instrument and core component of standardized training of general practice residents. This article reviews the common model and innovations of teaching clinics of general practice in China, and analyzes their reported effectiveness in enhancing the capabilities of consultation of resident physicians, the teaching capabilities of general practice trainers, as well as satisfaction levels of involved participants. It outlines the challenges encountered in implementing teaching clinics, including inadequate teaching facilities and equipment, incomplete incentive system for teaching, difficulties in patient recruitment, and weaknesses in the teaching capabilities of trainers. To address these challenges, this article proposes corresponding strategies based on realistic needs, including the improvement of facilities and equipment in teaching clinics, the establishment of incentive systems for teaching clinics, the expansion of patient recruitment channels for teaching clinics, and the enhancement of training for trainers' teaching capabilities. This is envisaged to provide both theoretical bases and practical guidance for the effective execution and standardized development of teaching clinics in general practice residency training bases.
3.Application of healthcare failure mode and effect analysis in preventing nursing interruption with negative outcome in operating room
Zhenya ZOU ; Xiaoyang ZHOU ; Hongxiang DUAN ; Chengcheng QIAN ; Cunbao GUO ; Jinbao MAO
Chinese Journal of Practical Nursing 2023;39(14):1041-1047
Objective:To explore the effect of healthcare failure mode and effect analysis (HFMEA) in reducing the incidence of nursing interruption with negative outcome in operating room, so as to maximize the smooth progress of the surgical process.Methods:This was a quasi experimental study. The gastrointestinal surgery room of Shandong Provincial Hospital Affiliated to Shandong First Medical University was selected for the study. According to the surgical sequence, 38 surgeries performed in the gastrointestinal surgery suite from August 15-30, 2021 were set as the control group, and the conventional healthcare cooperation model process was implemented; 42 surgeries performed from September 15-30, 2021 were set as the intervention group, and the operating room under the HFMEA model was implemented negative outcome care disruption event management process.A video tracking method combined with a surgical care disruption event register was used to investigate the occurrence of negative outcome care disruption events in the operating room, comparing the number, duration, source of disruption events and the incidence of near miss events in the operating room between the control group and the intervention group.Results:In the control group, there were 38 observed surgeries, 190 negative outcome care interruptions, negative outcome interruptions of (5.26 ± 1.02) min duration, and no near misses; in the intervention group, there were 42 observed surgeries, 84 negative outcome care interruptions, negative outcome interruptions of (2.06 ± 0.08) min duration, and no near misses. There were statistically significant differences in the number, duration of negative outcome care interruptions between the intervention group and the control group ( χ2 = - 18.71, t = - 20.28; all P<0.01). There was statistically significant difference in the source of negative outcome care interruptions between the intervention group and the control group ( χ2 = - 12.71, P<0.01). Conclusions:HFMEA model can effectively reduce the number of negative nursing interruptions in the operating room, shorten the duration of interruptions, and minimize potential safety hazards caused by nursing interruptions, which is conducive to ensuring the safety of patients.
4.Correlation between changes of swallowing function in oral and pharyngeal phases, and aspiration in stroke patients based on videofluroscopic swallowing study
Zhenya LI ; Jie SUN ; Pengfei GUO ; Guangming WANG
Chinese Journal of Rehabilitation Theory and Practice 2023;29(8):933-939
ObjectiveTo analyze the correlation between the changes of swallowing function and aspiration in stroke patients using videofluroscopic swallowing study. MethodsFrom January, 2014 to December, 2021, 240 stroke patients who underwent videofluroscopic swallowing study in the radiology department of Xuzhou Central Hospital were retrospectively analyzed. They were divided into aspiration group (n = 108, ≥ grade 5) and non-aspiration group (n = 132, < grade 5) according to Rosenbek Penetration/Aspiration Scale (PAS). The swallowing function changes in the oral and pharyngeal phases were compared between two groups according to Videofluoroscopic Dysphagia Scale, the risk factors of aspiration were analyzed using Logistic multivariate regression. ResultsThere were significant differences in incomplete lip closure, impaired bolus formation, apraxia, incomplete tongue-to-palate contact, premature bolus loss, prolonged oral transit time, delayed triggering of pharyngeal swallow, epiglottis folding dysfunction, pyriform sinus residue, and coating of pharyngeal wall (χ2 > 5.802, P < 0.05). Prolonged oral transit time (OR = 3.964, P = 0.036), delayed triggering of pharyngeal swallow (OR = 5.684, P < 0.001), epiglottis folding dysfunction (OR = 11.571, P < 0.001) and pyriform sinus residue (OR = 4.524, P = 0.002) were correlated with aspiration. ConclusionProlonged oral transit time, delayed triggering of pharyngeal swallow, epiglottis folding dysfunction and pyriform sinus residue are risk factors of aspiration after stroke.
5.A case of neurofibromatosis complicated with small bowel obstruction.
Mao LINGNA ; Guo QINGQU ; Wang GUIFENG ; Song ZHENYA
Journal of Zhejiang University. Medical sciences 2016;45(3):297-301
Neurofibromatosis type 1(NF-1) with gastrointestinal stromal tumor (GIST) is a rare case in clinical practice. But it is even rarer that the GIST tumor in this case is so large that it cause small intestinal obstruction. Here we report such a male case of NF-1,with positive family history of NF-1 and nodules all over the patient's skin and abdominal cavity. The patient came to hospital with a sudden upper abdominal pain and nausea and vomiting over 5 d. Abdominal computerized tomography (CT) showed that there were numerous nodules of different size in his abdominal cavity. And the largest one is about 10 cm in diameter,which oppressed the small bowel and caused the small bowel mesenteric volvulus and obstruction of the bowel. Finally,the tumor was pathologically proved to be a GIST tumor but not NF nodule. The patient stays healthy until now after operation.
6.Effect of sorafenib combined with thalidomide on angiogenesis in chick chorioallantoic membrane
Zhenya GUO ; Junfeng YE ; Qiankun XIE
Journal of Clinical Hepatology 2016;32(5):908-910
ObjectiveTo investigate the effect of sorafenib and/or thalidomide on angiogenesis in chick chorioallantoic membrane (CAM). MethodsWhite eggs incubated for 7 days were used to establish a CAM model. The model eggs were randomly divided blank control group, sorafenib group, thalidomide group, and sorafenib/thalidomide group. After treatment, each egg was incubated for another 2 days. The CAM samples were collected and fixed to take their pictures under a microscope, and the vascular coverage of each sample was calculated. Comparison between these groups was made by analysis of variance, and comparison between each two groups was made by SNK-q test. ResultsThe thalidomide group or sorafenib group had significantly lower vascular coverage than the blank control group (30.2%±2.9% or 26.5%±2.1% vs 38.3%±2.7%, P<0.05). The sorafenib/thalidomide group had significantly lower vascular coverage than the thalidomide group or sorafenib group (12.6%±1.5% vs 30.2%±2.9% or 26.5%±2.1%, P<0.05). ConclusionBoth sorafenib and thalidomide have a good anti-angiogenic effect on CAM, but a combination of the two drugs shows better efficacy.
7.Research progress in causes of congenital biliary atresia
Zhenya GUO ; Ruoyan ZHANG ; Mingjiang LIU
Journal of Clinical Hepatology 2015;31(8):1343-1346
Congenital biliary atresia is considered a neonatal rare disease with multiple causes and phenotypes, whose pathogenesis remains unclear. At present, the etiological study of congenital biliary atresia mainly focuses on viral infection, immune disorder, and dysplasia. This paper summarizes the main etiological hypotheses about congenital biliary atresia nowadays and the connections between them. The research progress provides valuable clues and evidence for the etiology and control of this disease.
8.Autologous bone marrow-mononuclear cell transplantation after the bone marrow stimulation in the treatment of thromboangiitis obliterans
Xuefeng LI ; Zhenya SHEN ; Yongquan GU ; Jian ZHANG ; Hengxi YU ; Lianrui GUO ; Zhu TONG ; Shijun CUI ; Yingfeng WU ; Zhonggao WANG
Clinical Medicine of China 2011;27(7):716-720
Objective To investigate the effect and safety of autologons bone margow-mononuclear cell (BM-MNC)transplantation after the bone marrow stimulation in patients with thromboangiitis obliterans (TAO).Methods The bone marrows of 12 patients were stimulated by an injection of the recombinant human granuloeyte-macmphage colony-stimulatory factor(GCSF)for 3-5 days.150-200 ml bone marrow was drown from the iliac spine and the autologous BM-MNC were obtained in each patients.Fifteen lower limbs of 12 patients received implantation of the autologous BM-MNC by an intramuscular iniecdon.A series of subjective indexes(including improvement of pain and cold sensation)and objeetive indexes [including increase of ankle braehial index(ABI),transcutaneons oxygen pressure(TcPO2)and improvement of foot skin ulcer] were used to evaluate the effects.Results The outcomes were evaluated after 2 months of transplantation.The pain-relief rate and the cold feeling improvement rate were 86.7%(13/15)and 93.3%(14/15)respectively.The ABI were 0.38 ±0.05 vs.0.61 ±0.14(P<0.05)before transplantation and 2 months after transplantation respectively.increased in 66.7%(10/15)limbs.The TcPO2 of the ischemic legs increased from(27.47±2.85)mm Hg to(43.53 ±8.38)mm Hg(t=-7.03,P<0.05)after the transplantation,and the improvement rate of TcPO2 was 93.3%(14/15).Skin ulcers in improved in 8/9 limbs.Twelve patients were followed up for all average period of 10 months.The patients'symptoms improved in 80.0%(12/15)limbs,as to the objective index the ABI was0.57±0.13,TcPO2 was(42.07 ±7.81)mm Hg,which improved significandy compared to before treatment(t=-5.33,-7.80,Ps<0.05).skin ulcer healing rate was 66.7%(6/9).The ischemic symptoms in 2 patients were not relieved.There WBS no mortality and high level amputation in all subjects.The complications,such as proliferative retinopathy,malitpmnt tumor,myocardial infarction,stroke or hemangioma were not found in any patients.Conclusion In patients with TAO,intramuscular transplantation of autologous BM-MNC after the bone marrow stimulation has advantages of less bone marrow aspiration,more mononuclear cell content and relatively high safety.It may be a new and effective method to alleviate symptoms and accelerate the healing of skin ulcer.
9.Combination of acupuncture, cupping and medicine for treatment of fibromyalgia syndrome: a multi-central randomized controlled trial.
Zhen-Ya JANG ; Chang-Du LI ; Ling QIU ; Jun-Hua GUO ; Ling-Na HE ; Yang YUE ; Fang-Ze LI ; Wen-Yi QIN
Chinese Acupuncture & Moxibustion 2010;30(4):265-269
OBJECTIVETo evaluate the clinical effect of combination of acupuncture, cupping and medicine for treatment of fibromyalgia syndrome.
METHODSBy using multi-central randomized controlled method, 186 cases were randomly divided into an acupuncture combined with cupping and western medicine group (group A), an acupuncture combined with cupping group (group B) and a western medicine group (group C) and treated continuously for 4 weeks. The treatment of acupuncture combined with cupping was produced by acupuncture at five mental points and moving cupping on the Hechelu of the back, once evrey other day, thrice each week, and the western medicine therapy by oral administration of Amitriptyline, once each day. The scores of McGill Pain Questionnaire (MPQ), the amount of tenderness point and the time of producing effect were compared and the therapeutic effects were assessed with the Hamilton Depression Scale (HAMD).
RESULTSThe cured and markedly effective rate was 65.0% (39/60) in the group A, which was superior to 15.9% (10/63) in the group B and 16.1% (9/56) in the group C (both P < 0.001). After treatment, the scores of MPQ and HAMD and the amount of tenderness point all decreased in the three groups, group A being significantly better than group B and group C, and the time of producing effect in the group A was more earlier than those in the group B and the group C.
CONCLUSIONThe therapeutic effect of combination of acupuncture, cupping and medicine on fibromyalgia syndrome is superior to that of the simple acupuncture combined with cupping or the simple medicine.
Acupuncture Points ; Acupuncture Therapy ; Adult ; Amitriptyline ; therapeutic use ; Antidepressive Agents, Tricyclic ; therapeutic use ; Combined Modality Therapy ; Female ; Fibromyalgia ; drug therapy ; therapy ; Humans ; Male ; Middle Aged ; Young Adult
10.Transplantation of autologous bone marrow mesenchymal stem cells modified with AKT1 for treating pig ischemic cardiomyopathy
Yunsheng YU ; Shiqiang GUO ; Guiping YU ; Wenxue YE ; Haoyue HUANG ; Yihuan CHEN ; Fei HUA ; Yongquan GU ; Zhenya SHEN
Chinese Journal of Tissue Engineering Research 2009;13(49):9616-9624
BACKGROUND: A great quantity of cell loss in early stage following stem cell transplantation can significantly affect transplantation effect. Presently, it is confirmed that overexpression of AKT1 gene significantly inhibit cell apoptosis. OBJECTIVE: To explore whether AKT1 gene overexpression can block stem cell apoptosis under hypoxic condition following pig autologous bone marrow mesenchymal stem cell (BMSC) transplantation, and the effect of repairing damaged myocardium. DESIGN, TIME AND SETTING: The randomized controlled animal study was performed at the Soochow University from August 2005 to February 2007.MATERIALS: A total of 24 healthy male Meishan pigs were supplied by the Animal Experimental Center of Soochow University. METHODS: The CDS (regulation domin of AKT1) AKT1-cDNA fragment was amplified. Lentivector Packaging Kit was used to transfect BMSCs after synthesized with pCDH1-AKT1 shuttling plasmid. Following BrdU labeling, models of myocardial infarction were constructed by occluding the distal left anterior descending coronary artery in pigs with gelatin sponge. 4 weeks later, pigs were randomly divided into four groups: the model control group, the DMEM group, the BMSCs group, and the AKT-transfected group. In model control group, there was no other injection after occluding the left anterior descending coronary artery. In the DMEM group, 5 mL DMEM was injected into the coronary artery. 5 mL BMSCs (1×10~7 cells) were infused into the coronary artery in the BMSCs group. 5 mL BMSCs transfected with the AKT1 gene were injected in the AKT-transfected group MAIN OUTCOME MEASURES: Western blot analysis and real time RT-PCR were used to test the plasmid. The cardiac function was evaluated by magnetic resonance image. Histological characteristics of the myocardium were observed using immunohistochemistry. Serum vascular endothelial growth factor and transforming growth factor β1 levels were determined by ELISA. RESULTS: AKT1-cDNA was cloned into pCDH1-MCS1-EF1-copGFP and the sequence was confirmed in comparison with the published one. AKT mRNA expression could be detected distinctly 24 and 48 hours after transfecting cells. The expression of AKT1 intensity in MSCs remained strong 2 weeks later with detected by real time RT-PCR and Western blot analysis. AKT1-mRNA transcriptional levels were 120 times of primary cells. Before the cell implantation, the left ventricular end-diastolic dimension increased and the stroke volume decreased in the myocardial infarction hearts. The cardiac function was significantly improved after cell implantation, and the implanted MSCs prevented the infarct region from thinning and expanding, improved contraction and increased perfusion in all groups relative to the control hearts. The left ventricular chamber size was smaller in the hearts with being transplanted cells than that in the control hearts. Moreover, the improvement was even markedly greater in AKT-transfected group (P < 0.05). Hematoxylin-eosin staining results showed that fibering was significant in the model control group and DMEM group. Island-like myocardium was observed in the infarct zone of the BMSCs group and AKT-transfected group, and plenty of small vessels-shape structure was detected in the AKT-transfected group. Immunohistochemistry demonstrated that Von Willebrand Factor (vWF) and Cx-43 expression was determined in the myocardium in the BMSCs group and AKT-transfected group, and the proportion of BrdU and Cx-43-positive cells to BrdU-positive cells was significantly greater in the AKT-transfected group compared with the BMSCs group 4 weeks following transplantation (P < 0.05). Following cell transplantation, vascular endothelial growth factor levels were gradually increased, peaked at 1 week, gradually decreased, and reached a normal level at 4 weeks. Transforming growth factor p1 levels were gradually reduced, and significantly less than the model control group, DMEM group 4 weeks later (P < 0.05), and significantly lower than that pretransplantation (P < 0.05).CONCLUSION: Using lentiviral vector to construct with AKT1 gene could stably make BMSCs overexpress AKT1. The BMSCs engraftment in host myocardium might improve the left ventricle function by attenuating the contractile dysfunction and pathologic thinning in this model of left ventricular wall infarction. AKT1 overexpression can significantly improve cardiac function following infarction.

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