The innate immune sensor NLRP3 inflammasome overactivation is involved in the pathogenesis of ulcerative colitis. PGAM5 is a mitochondrial phosphatase involved in NLRP3 inflammasome activation in macrophages. However, the role of PGAM5 in ulcerative colitis and the mechanisms underlying PGAM5 regulating NLRP3 activity remain unknown. Here, we show that PGAM5 deficiency ameliorates dextran sodium sulfate (DSS)-induced colitis in mice via suppressing NLRP3 inflammasome activation. By combining APEX2-based proximity labeling focused on PGAM5 with quantitative proteomics, we identify NEK7 as the new binding partner of PGAM5 to promote NLRP3 inflammasome assembly and activation in a PGAM5 phosphatase activity-independent manner upon inflammasome induction. Interfering with PGAM5-NEK7 interaction by punicalagin inhibits the activation of the NLRP3 inflammasome in macrophages and ameliorates DSS-induced colitis in mice. Altogether, our data demonstrate the PGAM5-NEK7 interaction in macrophages for NLRP3 inflammasome activation and further provide a promising therapeutic strategy for ulcerative colitis by blocking the PGAM5-NEK7 interaction.

Gypenosides, structurally analogous to ginsenosides and derived from a sustainable source, are recognized as the principal active compounds found in Gynostemma pentaphyllum, a Chinese medicinal plant used in the treatment of the metabolic syndrome. By bioactive tracking isolation of the plants collected from different regions across China, we obtained four new gypenosides (1-4), together with nine known gypenosides (5-13), from the methanol extract of the plant. The structures of new gypenosides were elucidated by one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) spectra, complemented by chemical degradation experiments. Through comprehensive evaluation involving COL1A1 promoter assays and PP2Cα activity assays, we established a definitive structure-activity relationship for these dammarane-type triterpenoids, affirming the indispensability of the C-3 saccharide chain and C-17 lactone ring in effectively impeding extracellular matrix (ECM) deposition within hepatic stellate cells. Further in vivo study on the CCl₄-induced liver damage mouse model corroborated that compound 5 significantly ameliorated the process of hepatic fibrosis by oral administration. These results underscore the potential of dammarane-type triterpenoids as prospective anti-fibrotic leads and highlight their prevalence as key molecular frameworks in the therapeutic intervention of chronic hepatic disorders.
Animals ; Mice ; Gynostemma ; Liver Cirrhosis/drug therapy* ; Triterpenes/pharmacology* ; Ginsenosides ; Extracellular Matrix ; Dammaranes

Objective:To investigate the best neutralization ratio of protamine and heparin during off-pump coronary artery bypass grafting(OPCABG) by analyzing the advantages and disadvantages of heparin residue after OPCABG.Methods:From July 2018 to January 2019, 112 patients undergoing elective OPCABG were included in this study. The patients’ whole blood was drawn at 2 time points, including before entering operating room and entering intensive care unit, to receive thrombelastography(TEG) and heparinase-modified thromboelastography(hmTEG) . Conventional coagulation indexes such as activated coagulation time(ACT) were also detected. All the patients were divided into 3 groups, the non-heparin residue group(30 cases), heparin residue group 1(42 cases) and heparin residue group 2(40 cases) according to the laboratory results of TEG, hmTEG and ACT. We observed the dosage of each group of protamine and heparin, as well as the ratio of heparin and protamine. The changes of R time in TEG and ACT between 3 groups were analyzed and compared. Postoperative chest tube drainage at postoperative 12 h and 48 h, cTnI peak value, incidence of perioperative myocardial infarction(MI), incidence of reoperation and poor wound healing, amount of blood loss and transfusion, and acute renal injury were compared between the 3 groups.Results:No significant trio-group differences existed in basic clinical characteristics(all P>0.05). Postoperative R(CKH)time was similar in the 3 groups( P>0.05). Comparing with heparin residue group 1 and heparin residue group 2, the ACT after protamine neutralizing heparin and postoperative R time were decreased, the dosage of protamine, ratio of heparin and protamine, cTnI peak value were increased in the non-heparin residue group( P<0.05). Comparing with heparin residue group 2, the dosage of heparin, postoperative chest tube drainage at postoperative 12h and 48h, amount of blood transfusion and transfusion probability were significantly decreased in non-heparin residue group( P<0.05), but compared with group 1 of heparin residue, there was no significant difference in the above indexes( P>0.05). The perioperative myocardial infarction, incidence of reoperation and poor wound healing, postoperative acute renal injury and time of in ICU stay showed no significant differences between the 3 groups( P>0.05). Conclusion:Moderate heparin residue after OPCAB suggests that it has myocardial protective effect, and does not significantly increase the risk of bleeding. A large number of heparin residues can affect the coagulation function and lead to bleeding tendency, increase the amount of blood loss and transfusion. It is reasonable to make ACT after protamine neutralize heparin higher than the level of ACT before operation, and not higher than 20% of the level before operation.

Objective:To investigate the effect of head model in improving the photographic ability of interns during the photographic training of oral facial image in pediatric dentistry.Methods:A total of 60 interns of stomatology school affiliated to Xinjiang Medical University were randomly divided into head model training group, mutual training group and clinical probation group for photographic training. After the training, the interns in the three groups were evaluated for the photographic time, the level of photos, etc., by the training test and satisfaction level of volunteers. Besides, the head model training group was conducted by questionnaire survey. One-way analysis of variance and least significant difference analysis were used to analyze the data between groups by SPSS 17.0 software.Results:There was no statistical difference between the head model training group and the mutual training group in photographic time and level of photos, while both of them were much better in the head model training group and mutual training group than in the clinical probation group ( P<0.05). There was no statistical difference between the head model training group and the mutual training group in the satisfaction level, while that was lower in the head model training group than in the clinical probation group ( P<0.05). According to the questionnaire survey, most interns in the head model training group acknowledged its effects. Conclusion:The use of head model can help improve the oral photographic ability, and promote the teaching effect and efficiency in photographic training.

Objective To investigate the effects of radical prostatectomy on the overall survival (OS)and tumor-specific survival in prostate cancer(PCa)patients aged 75 years and older.Methods Clinical data of patients aged 75 and older with localized PCa from Surveillance,Epidemiology,and End Results(SEER)Database from 2004 to 2016 were retrospectively analyzed.There were 17 899 cases of PCa undergoing radical prostatectomy and 3 648 cases of PCa without surgery in this study.The OS and prostate cancer-specific survival(PSS)were compared between the surgery group and the nonsurgery group.Results For 75-79-year-old patients with high-risk localized PCa,the OS and PSS in the surgery group were better than in the non-surgery group (OR =1.49,95 ％ CI:1.22 ～ 1.82,P ＜ 0.01;OR=1.43,95％CI:1.09～2.04,P＜0.05).For patients aged 75-79 years with low-risk PCa and patients aged 80 years and older with low-,middle-,or high-risk PCa,the OS was worse in the surgery group than in the non-surgery group(OR =0.54,95％CI:0.38～0.76,P＜0.01;OR =0.47,95％CI:0.34～0.66,P＜0.01;OR =0.58,95％CI:0.44～0.78,P＜0.01;OR =0.59,95％CI:0.51 ～0.68,P＜0.01).For patients aged 75-79 years with low-or medium-risk PCa and patients aged 80 years and older with medium-risk PCa,there was no statistical difference in PSS between the surgery and non-surgery groups(P＞0.05).Conclusions Age limits for prostatectomy should be extended as a result of increasing average life expectancy.Patients aged 75-79 years with high-risk PCa can be considered for surgical treatment,while it should not be recommended for patients aged 75-79 years with low-or medium-risk localized PCa or aged more than 80 years.Many factors should be considered in making treatment decisions for prostate cancer.

Objective    To explore the relationship between glycated hemoglobin (HbA1c) level and blood glucose fluctuations after coronary artery bypass grafting (CABG) and adverse events in non-diabetic patients, thus providing theoretical support for intensive preoperative blood glucose management in patients undergoing CABG surgery. Methods    A total of 304 patients undergoing CABG with or without valvular surgery from October 2013 to December 2017 were enrolled in this prospective, single-center, observational cohort study. We classified them into two different groups which were a low-level group and a high-level group according to the HbA1c level. There were 102 males and 37 females, aged 36–85 (61.5±9.5) years in the low-level group, and 118 males and 47 females aged 34–85 (63.1±9.4) years in the high-level group. The main results were different in hospital mortality and perioperative complications including in-hospital death, myocardial infarction, sternal incision infection, new stroke, new-onset renal failure and multiple organ failure. To assess the effects of confounding factors, multivariate logistic regression analysis was used. Results     Postoperative blood glucose fluctuation was more pronounced in the high-level group than that in the low-level group before admission [0.8 (0.6, 1.2) mmol/L vs. 1.0 (0.8, 1.8) mmol/L, P<0.01]. This study also suggested that the  incidence of major adverse events was significantly lower in the low-level group compared with the high-level group (P=0.001). Multivariate logistic regression analyses to correct the influence of other confounding factors showed that HbA1c (OR=2.773, P=0.002) and postoperative blood glucose fluctuations (OR=3.091, P<0.001) could still predict the occurrence of postoperative adverse events. Conclusion    HbA1c on admission can effectively predict blood glucose fluctuations in 24 hours after surgery. Secondly, HbA1c on admission and postoperative blood glucose fluctuations can further predict postoperative adverse events. It is suggested that we control the patient's preoperative HbA1c at a low level, which is beneficial to control postoperative blood glucose fluctuation and postoperative adverse events.

Objective: To investigate the predictive value of serum high-mobility group box-1 protein (HMGB1) for hemorrhage transformation (HT) after intravenous thrombolysis in patients with acute ischemic stroke. Methods: From February 2017 to September 2019, patients with acute ischemic stroke underwent intravenous thrombolysis in Lixin County People's Hospital, Bozhou, Anhui Province were enrolled prospectively. In the morning of the day after admission, fasting blood was collected to detect the level of serum HMGB1. Twenty-four hours after intravenous thrombolysis, CT reexamination was performed to determine whether HT occurred. The demographic and baseline clinical data were compared between the HT group and the non-HT group. Multivariate logistic regression analysis was used to determine the independent risk factors for HT after thrombolysis. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of serum HMGB1 level to HT. Results: A total of 182 patients were enrolled in the study, including 22 in the HT group and 160 in the non-HT group. The age, fasting blood glucose, serum HMGB1 level, and the proportion of history of atrial fibrillation and regular antiplatelet medication before onset in the HT group was significantly higher than those in the non-HT group, and the differences were statistically significant (all P<0.05). Multivariate logistic regression analysis showed that the increased serum HGMB1 level (odds ratio [OR] 2.145, 95% confidence interval[CI] 1.467-3.138; P=0.002), taking antiplatelet drugs regularly before onset (OR 5.496, 95% CI 1.700-17.768; P=0.004) and increased baseline fasting blood glucose level (OR 1.333, 95% CI 1.024-1.736; P=0.033) were the independent risk factors for HT after intravenous thrombolysis. ROC curve analysis showed that the area under the curve of serum HMGB1 level predicting HT after intravenous thrombolysis was 0.788 (95% CI 0.721-0.845; P<0.001). The sensitivity and specificity were 72.73% and 82.50%, respectively, when the best cutoff value was 7.97 μg/L. Conclusion The increased baseline HMGB1 level may predict the risk of HT after intravenous thrombolysis in patients with acute ischemic stroke.

Objective To explore the factors affecting the effect of first stage treatment of sacral neuromodulation.Methods A retrospective analysis of 39 patients with dysuria related diseases from April 2012 to January 2016 was performed.There were 14 male patients and 25 female patients.Their age ranged from 15 to 86 years old,mean 54 years old.The types of disease were bladder pain syndrome/interstitial cystitis in 1 8 cases,idiopathic urinal retention in 5 cases,overactive bladder in 8 cases,neurogenic bladder in 6 cases,and urgent incontinence in 2 cases.All patients were treated by behavioral therapy,drug therapy,and at least one recomnended treatment method.All previons treatments were ineffective.All patients were collected baseline medical records.The voiding diary,visual analogue pain score,quality of life score,anxiety score and other information before and after the first stage surgery and the last follow-up after the second stage surgery were also collected.Results A total of 39 patients were enrolled in this study.27 patients (69％)who were satisfied with the effect of the first stage of surgery were treated with the second stage surgery,and 12 patients (31％)who were not satisfied with the results of the first phase operation did not undergo the second phase operation.The second stage implantation rate was 69％.The average experience time was (21.6 ± 3.0) days.In the single first stage implantation group,there were 6 males and 6 females,including interstitial cystitis in 3 cases,overactive bladder in 3 cases,neurogenic bladder in 4 cases,idiopathic urinary retention in 1 cases and urgent incontinence in 1 cases.2 cases have a history of pelvic and urinary surgery and 10 cases dont.The average BMI was 21.8 ± 3.7 kg/m2,and mean age was(44.5 ± 19.1) years old.The average preoperative anxiety score was 33.7 ± 5.3 and the average pain score of preoperative was 8.0 ± 1.0.The average quality of life score was 4.6 ±0.8 and the average daily nunber of urine was 23.1 ± 12.8.The average mean urine volume was (89.4 ± 33.0) ml,the average frequency of nocturia was 10.3 ± 5.5,the average medical history time was (100.6 ± 125.5) months.In the second stage implantation group,there were 8 males and 19 females,including interstitial cystitis in 15 cases,overactive bladder in 5 cases,neurogenic bladder in 2 cases,idiopathic urinary retention in 4 cases,and urgent incontinence in 1 cases.10 cases have a history of pelvic and urinary surgery while 17 cases don't.Average BM1 was (24.1 ± 2.6) kg/m2,and mean age was(57.9 ± 16.8) years old.The average preoperative anxiety score was 27.7 ± 5.9,the average pain score of preoperative was 7.9 ± 1.6.The average quality of life score was 5.3 ± 0.9 the average daily urinary number was 30.6 ± 14.2.The average mean urine volume was (64.8 ± 37.4) ml and the average frequency of nocturia was 13.3 ± 9.2.The average history of time was (83.0 ± 56.0) months.Patients who were implanted with permanent sacral neuromodulation system were mostly older (P =0.034),with higher BMI (P =0.043) and lower anxiety (P =0.008).There were no statistically significant differences in gender(P =0.287),disease(P =0.116),the daily urinary frequency (P =0.140),the average urine volume (P =0.470),nocturia freqnency (P =0.068),pain scores (P =0.880),surgical history (P =0.276)and the medical history time (P =0.116) between patients who underwent first stage surgery only and second stage surgery.Conclusion BMI,age and anxiety may be the factors that affect the outcome of the first stage treatment of sacral neuromodulation.

Objective To obtain alpaca single domain antibody targeting Her2.Methods An alpaca was immunized with human recombination Her2 protein mixed with Freund's adjuvant.Total RNA was extracted from the alpaca's blood and was used to synthesize first strand cDNA.Single domain antibody variable region (VHH) gene of the alpaca was amplified by PCR and cloned into pMES4 vector for library construction.After screening, E.coli BL21 (DE3) was transformed with selected clones and was induced with IPTG for the expression of recombinant proteins.The nanobody was purified by nickel ion affinity chromatography column.The affinity of the nanobodies to Her2 was tested.Results After the second round of screening, two antibody clones were selected, H3 and H5.The affinity of H5 was 8.106×10-10mol/L.Histochemistry results showed that H5 could recognize Her2 antigen in breast tumor tissue.Conclusion An Her2 specific nanobody derived from alpaca is obtained through phage display library screening, which can recognize human Her2 antibody in human breast tumor tissue.

Objective To investigate the status of geriatric doctors' acknowledge and treatment of outpatients with lower urinary tract symptoms in 15 Chinese cities.Methods The investigation was conducted in 15 Chinese cities and involved 1056 geriatric doctors from December 2013 to February 2014.The questionnaire survey was made in behavior,attitude,skill and knowledge(BASK)of LUTS.The geriatric doctors participated in the investigation by answering the questionnaires about acknowledge for definition,etiology,diagnosis and treatment of the LUTS,and in results discussion,which was aimed at improving participants' cognition for diagnosis and treatment of elderly LUTS and at strengthening the practice.The final objective was to promote diagnosis standardization and to improve the level of clinical diagnosis and treatment for the elderly 1UTS.Results 95.9％ of geriatric doctors considered that they knew well the main clinical manifestations of LUTS.However,34.3 ％ of geriatric doctors were able to classify the symptoms of LUTS correctly.More than 90.0 ％ of geriatric doctors considered that the causes of LUTS were variable and they mastered the common cause of LUTS.But,38.0％ of them were able to completely master the causes of LUTS and 35.5％ would actively ask outpatients about the symptoms.70.0％ of the doctors thought they were familiar with the initial manifestations of LUTS and benign prostatic hypertrophy(BPH).However,many Chinese geriatric doctors didn't follow up the guidelines and 30.0％ of them failed to evaluate the severity of LUTS via IPSS(International Prostatic Symptom Score).75.8％ of geriatric doctors considered that they would give the patients the best treatment options by comprehensive assessment.However,60.0％ of them didn't know that α1 receptor blocker was the first line of treatment option of patients with moderate severe LUST.More than half of them were unclear that the patients with prostate volume under 40 ml could be treated by α1 receptor blocker.82.3％ of geriatric doctors considered that LUTS and hypertension should be treated respectively.But,55.0％ of them didn't know that ALLHAT trial has proved that Doxazosin would increase the risk of cardiovascular event.Conclusions The geriatric doctors are now able to pay attention to outpatients with LUTS,but still should further strengthen their acknowledge on the definition,cause,diagnosis and treatment of LUTS.