OBJECTIVE:To study the effect of long-term follow-up of Valsartan and amlodipine tablets(Ⅰ)on blood pressure control and renal protection of patients with refractory hypertension. METHODS:120 patients with refractory hypertension were di-vided into control group and observation group according to the patients’wishes,with 60 cases in each group. All patients accepted the triple therapy of amlodipine+valsartan+hydrochlorothiazide and life-style intervention;at the time of discharge from hospital, the blood pressure was well controlled. After discharge from hospital,control group was given amlodipine;observation group was given Valsartan and amlodipine tablet (Ⅰ) orally,1 tablet each time,qd,and dose increasing according to blood pressure,with maximal dose no more than 2 tablets. With 18 months of follow-up,blood pressure and renal function indexes of 2 groups were ob-served at different time points,and blood pressure control rate and the rate of renal function injury were also observed at the last follow-up;the occurrence of ADR was observed. RESULTS:2 cases and 3 cases were follow-up loss in observation group and con-trol group,respectively. With 12 and 18 months of follow-up,24 h systolic pressure,24 h diastolic pressure and 24 h urine protein of 2 groups increased significantly while creatinine clearance rate decreased significantly compared with before discharge;but the in-dexes of observation group was better than that of control group,with statistical significance(P<0.05). At last follow-up,the rate of blood pressure in observation group was significantly higher than in control group(84.5% vs. 52.6%),the rate of renal function injury was significantly lower than control group(8.6% vs. 24.6%),with statistical significance(P<0.05). There was no statisti-cal significance in the incidence of ADR between 2 groups(P>0.05). CONCLUSIONS:Valsartan amlodipine tablet(Ⅰ)has obvi-ous advantages in long-term follow-up of blood pressure control of patients with refractory hypertension. It can significantly reduce the incidence of renal function injury with good safety.

To investigate the influence of Drynaria total flavonoids on proliferation and apoptosis of osteoblasts in tumor necrosis factor-α (TNF-α)- mediated medium, so as to explore the mechanism of Drynaria total flavonoids in preventing and treating osteoporosis of rheumatoid arthritis.

Objective To evaluate the influence of epimeric glycyrrhizic acid on production of endothelin-1 (ET-1) in the lungs induced by ischemia-reperfusion(I/R) injury.Methods Twenty healthy long-ear white rabbits of both sexes, weighing 1.1-2.1kg were randomly divided into 2 groups: group I I/R alone ( n = 10) and group II I/R + epimeric glycyrrhizic acid (n = 10). The animals were anesthetized with thiopental 25 mg?kg-1 and tracheotomized and mechanically ventilated (FiO2 = 100% , VT = 10-13 ml?kg, RR = 20-30 bpm, I:E= 1: 1.2). Anesthesia was maintained with fentanyl, thiopental and vecuronium. Femoral artery was cannulated for continuous direct BP monitoring. MAP was maintained at 70-90 mm Hg during experiment. Right interval jugular vein was cannulated. Catheter was inserted into right atrium for fluid administration, blood sampling and right atrial pressure monitoring. Chest was opened and the hilum of right lung was mass-ligated to induce ischemia for 60 min and then released for reperfusion for 60 min. Epimeric glycyrrhizic acid 30 mg?kg-1 was given iv 30 min before ischemia of the right lung. Blood samples were taken from right atrium and femoral artery for determination of ET-1 concentration before ischemia of right lung (T0) and 1 and 5 min after right lung started being perfused (T1 , T2). At the end of 60 min reperfusion of the right lung, the animals were sacrificed and lungs (right and left) were removed for electron microscopic examination. Results In group 1 at T, the ET-1 levels in the blood from both femoral artery and right atrium were significantly higher than the baseline (T0) and the ET-1 concentration in the blood from femoral artery was significantly higher than that from right atrium. In group II there was no significant difference in blood ET-1 concentration between T0 and T, .Conclusion Ischemia-reperfusion induces increased production of ET-1 in the injured lung. Epimeric glycyrrhizic acid can inhibit the increase in the production of ET-1 in the induced by I/R.

Objective This study is aimed to explore the effect of rhTNFR:Fc and methotrexate (MTX)-rhTN FR:Fc on joint destruction of collagen-induced arthritis ( CIA ) rat by establishing CIA rat model which imitates pathogenic factors of rheumatoid arthritis (RA).Methods CIA rat model were developed by subcutaneous injection of bovine type Ⅱ collagen.The rats with inflammation scores of two or above were randomly divided into four groups:the sterilized water treatment group (0.4 ml/w,intra-peritoneal injection),the MTX treatment group (1 mg/w,intra-peritoneal injection),the rhTNFR:Fc treatment group(0.8 mg Biw,intra-peritoneal injection),the MTX + rhTNFR:Fc treatment group (MTX 1 mg/w and rhTNFR:Fc 0.8 mg Biw,intraperitoneal injection).After treatment for 8 weeks,the rats were sacrificed and took the ankle radiography.Micro-CT scan of proximal tibia was performed and hard-tissue slices were made,and then the ankle's bone damage of each group was observed in order to evaluate trabecular variation and bone quantity changes of proximal tibia.Statisstical analysis was conducted with ANK-q test.Results After treatment for 8 weeks,the percentage of trabecular area and the trabecular number of the rhTNFR:Fc treatment group and the MTX-rhTNFR:Fc treatment were [(29.1±0.3)％,(26.7±0.6)％,(4.4±0.5)/mm,(4.0±0.6)/mm] (P＜0.01),which were evidently higher than the sterilized water treatment group and MTX treatment group (P＜0.01).The trabecular separation of Etanercept treatment group and MTX-rhTNFR:Fc group was obviously less than the sterilized water treatment group and MTX treatment group [(12.9±0.5)％,(13.2±0.4)％ vs (2.0±0.3)/mm,(2.2t0.2)/mm] (P＜0.01).Conclusion rhTNFR:Fc and MTX-rhTNFR:Fc can remarkably inhibit joint destruction of CIA rat.And their effect on inhibiting of inflammation and increasing peri-articular bone quantity.In addition,they are effective on inhibiting the reduction of local trabecular structure and increase of trabecular separation.

Objective To investigate the optimal injury time point of cardiac arrest (CA) induced electrically, and establish a reproducible prolonged CA and cardiopulmonary resuscitation (CPR) model in pigs. Methods Forty healthy domestic male pigs were randomly divided into four groups, which were ventricular fibrillation (VF) 8, 10, 11, and 12 minutes groups, each group for 10 animals. In these groups, VF was induced by alternating current delivered to right ventricular endocardium and untreated for 8, 10, 11, and 12 minutes, respectively, followed by 6 minutes of CPR procedure. The resuscitation and survival outcomes were recorded. Hemodynamic parameters and arterial blood gases of animals after successful resuscitation were measured and recorded for 6 hours. Those successful resuscitation animals were regularly evaluated for the neurological deficit score (NDS) and survival outcomes every 24 hours till 96 hours after resuscitation. Results The shortest duration of CPR (minute: 6.9±1.3) and the highest successful ratio of the first defibrillation (7/10) were observed in group VF 8 minutes, and the ratio of successful resuscitation was 100%. The best coronary perfusion pressure (CPP) during the CPR, less neurological impairment, longer survival time, more stable hemodynamics, and shorter time for arterial pH and lactate level restoring to the original state after CPR were also observed in group VF 8 minutes, and no severe damage was found in those animals. The longest duration of CPR (minute:10.3±2.9) and the lowest successful ratio of the first defibrillation (1/10) were observed in group VF 12 minutes, and only 4 animals achieved restoration of spontaneous circulation (ROSC), and no animal survived to CPR 96 hours. The worst CPP during CPR and the highest NDS after resuscitation were also found in VF 12 minutes animals compared to those animals in the other groups. The injuries caused by ischemia and hypoxia in groups VF 10 minutes and VF 11 minutes were in between those of the groups VF 8 minutes and VF 12 minutes, and the duration of CPR were (7.0±2.1) minutes and (8.2±2.6) minutes. There were 9 and 7 animals achieved ROSC in groups VF 10 minutes and VF 11 minutes correspondingly, and 6 and 4 animals survived to 96 hours respectively. Obviously unstable hemodynamics was observed during the period of CPR 2 hours in the two groups. At CPR 1 hour, the heart rates (HR, beats/min) in groups VF 10 minutes and VF 11 minutes increased to 172 (155, 201) and 168 (136, 196) respectively, and the mean arterial pressures (MAP, mmHg, 1 mmHg = 0.133 kPa) declined to 97 (92, 100) and 81 (77, 100), the cardiac output (CO, L/min) decreased to 5.0 (4.0, 5.8), 3.7 (3.0, 5.4) correspondingly. Distinct injuries were found in the two groups [CPR 24-96 hours NDS in groups VF 10 minutes and VF 11 minutes: 180 (110, 255)-20 (0, 400) and 275 (223, 350)-240 (110, 400)], and the arterial pH of the two group decreased to 7.26±0.09 and 7.23±0.09 respectively, and the level of lactate (mmol/L) increased to 9.17±1.48 and 12.80±2.71 correspondingly at CPR 0.5 hour. Significantly lower pH was observed in group VF 11 minutes compared to group VF 8 minutes at CPR 0.5 hour (7.23±0.09 vs. 7.33±0.04, P < 0.05). The highest level of lactate (mmol/L) was also found at the same time point in group VF 11 minutes, which recovered to normal slowly, and was still significantly higher than groups VF 8, 10, 12 minutes (7.58±3.99 vs. 2.55±1.53, 2.13±2.00, 3.40±2.30, all P < 0.05) at CPR 4 hours. Conclusions The longer duration of CA was, the more severe damage would be, the longer CPR time would be required, and the harder of the animals to achieve ROSC. In this prolonged CA and CPR porcine model, 10-11 minutes for untreated VF, was an optimal time point with appropriate successful rate of resuscitation, survival outcomes, and post-resuscitation injuries. Therefore, we recommended 10-11 minutes might be the rational length of no-flow time in this model.

Objective To investigate the risk factors predicting pathology grade upgrading after radical prostatectomy using the 2014 International Society of Urologic Pathology (ISUP) grading system.Methods A total of 205 patients who underwent biopsy and radical prostatectomy from January 2017 to December 2018 were reviewed retrospectively.The median and range of the patients' age,PSA level,prostate volume,number of biopsy core examined,Gleason score and ISUP grade were 66 (45-81) years old,17.16(0.89-1254.00)ng/ml,36.4(4.1-152.1) rnl,10(1-15),7(6-10),and 3(1-5) respectively.The patients were divided into group of upgrading ISUP grade and group without upgrading ISUP grade.Multivariate Logistic regression analysis and receiving operating characteristic curve analysis were performed to identify predictors of ISUP upgrading and determine the optimal cut off value respectively.Result The median and range of Gleason score and ISUP grade after radical prostatectomy were 7 (6-10),and 3 (1-5) respectively.The radical prostatectomy ISUP grade upgraded in 73 (35.6％) out of 205 cases when compared with biopsy ISUP grade.Radical prostatectomy ISUP grades were concordant in 91 cases (44.4％) and downgraded in 41 cases(20.0％).Of 101 with biopsy ISUP grades less than or equal to 2,the ISUP grade of radical prostatectomy upgraded in 58 cases (57.4％),while radical prostatectomy ISUP grade upgraded in only 18 (26.9％) of 67 patients with biopsy ISUP grades of 3 or 4.Biopsy ISUP grades represent an independent predictor for ISUP grade upgrading after radical prostatectomy (OR =0.496,P ＜ 0.001).Conclusion Patients with biopsy ISUP grades less than or equal to 2 are at great risk of ISUP grade upgrading after radical prostatectomy.

Objective:To improve the awareness of cholesterol crystal embolism syndrome (CCE) inrheumatologists.Methods:The clinical characteristics of 40 Chinese CCE patients admitted to our department (one case) were summarize and in the literature (thirty-nine cases) were reviewed.Results:Among these 40 patients, 87.5%(35/40) were male and the mean age was (68±6) years. All patients suffered from athero-sclerosis and 87.5%(35/40) of them had precipitating factors such as endovascular intervention, vascular surgery, anticoagulant, or thrombolytic therapy. The clinical manifestations included renal insufficiency (90.0%, 36/40), blue toe syndrome (82.5%, 33/40), ulceration or gangrene (25.0%, 10/40), and livedo reticularis (15%, 6/40). Acute phase reactant was tested in 25 cases, of whom 84.0%(21/25) showed elevated C-reactive protein (CRP) and 56.0%(14/25) showed elevated erythrocyte sedimentation rate (ESR).Conclusion:Rheumatologists should be alert that CCE is one of the differential diagnosis of systemic vasculitis, especially for patients with severe atherosclerosis.

A 58-year-old male patient with angioimmunoblastic T-cell lymphoma developed a rash and skin tightness on the face, limbs, and trunk together with joint stiffness and dysfunction after 6 months of treatment with the programmed cell death protein-1 inhibitor camrelizumab. Laboratory tests revealed progressive eosinophilia over 6 months, with the eosinophil count increasing from 0.07×10 9/L to 3.3×10 9/L. Magnetic resonance imaging showed thickened skin of both forearms, while T 2-weighted imaging showed markedly increased signal intensity within the myofascia. Skin biopsy of the right forearm showed thickened and fibrosed fascia and infiltration of inflammatory cells, including lymphocytes, plasma cells, and eosinophils. The patient was diagnosed with immune checkpoint inhibitor (ICI)-induced eosinophilic fasciitis (EF). After beginning treatment with methylprednisolone (40 mg daily), methotrexate (10 mg/week), and baricitinib (4 mg daily), his symptoms of skin tightness and joint dysfunction significantly improved within 1 month, and his peripheral blood eosinophil count decreased to 0.17×10 9/L. ICI-induced EF is a rare immune-related adverse reaction. To date, only 20 cases have been reported in published foreign literature, and their clinical characteristics are summarized here. The time from ICI treatment to EF was 12 (8,15) months, and the main clinical manifestations included skin involvement ( n=19), joint dysfunction ( n=11), myalgia/muscle weakness ( n=9), and peripheral eosinophilia ( n=16). After treatment, the clinical symptoms of EF improved in 17 patients, and eosinophil counts returned to normal after 3 (1,8) months. EF is a dysfunctional adverse response to ICI therapy. Tumor patients undergoing immunotherapy should be monitored for symptoms of EF. Early treatment is essential for preventing complications.

OBJECTIVE: To explore the clinical and genetic characteristics of a Chinese pedigree affected by glycogen storage disease (GSD) type Ia with gout as the first manifestation. METHODS: Clinical and biochemical data of the pedigree were collected. Available members of the pedigree were subjected to gene sequencing, and the result was analyzed by bioinformatics software. The pedigree was followed up for five years. RESULTS: The proband was a young female manifesting recurrent gout flare, hypoglycemia, and hypertriglyceridemia. One of her younger brothers also presented with dysplasia and hepatic adenoma. Gene sequencing revealed that the proband and her younger brother both harbored c.1022T>A (p.I1e341Asn) and c.230+5G>A compound heterozygous variants of the G6PC gene , which were inherited from their father and mother, respectively. Among these, the c.230+5G>A is an intron region variant which was unreported previously, and bioinformatics analysis showed that it may impact mRNA splicing of the gene. The proband was treated with raw corn starch, allopurinol, and fenofibrate. Gout was well controlled, and she had given birth to a baby girl without GSD. CONCLUSION GSD Ia should be considered among young gout patients with hypoglycemia and hepatomegaly, for which gene sequencing is warranted. GSD Ia has a good prognosis after comprehensive treatment with diet and medicine.
China ; Female ; Glycogen Storage Disease Type I ; Gout/genetics* ; Humans ; Hypoglycemia ; Male ; Pedigree ; Symptom Flare Up

ObjectiveTo explore the occurrence of gasdermin D （GSDMD） -mediated pyroptosis and its effect on cell proliferation， migration and tubular formation abilities of synovial vascular endothelial cells （VEC） in rheumatoid arthritis （RA）. MethodsSynovium tissues from knee joints of 22 RA patients and 18 orthopaedic arthropathies （Orth. A） patients were collected. The level of activated GSDMD-NT segment in synovium was detected by Western blot. The clinical characteristics of RA patients were compared between high and low synovial GSDMD-NT groups. The cell localization of GSDMD in RA synovium was detected by immunofluorescence staining. RA synovial fluid was added to the culture of human umbilical vein endothelial cells （HUVEC） in vitro， and the level of apoptosis and expression of pyroptosis pathway proteins were detected. The effects of GSDMD on apoptosis， proliferation， migration and tubule formation of HUVEC cells were analyzed. ResultsGSDMD expression in RA synovium was significantly higher than that in Orth. A， and more severe joint destruction and higher microvascular count score were found in RA patients with high GSDMD-NT expression. Synovial VEC had positive expression of GSDMD. Stimulation with RA synovial fluid could induce GSDMD-mediated pyroptosis in HUVEC， increased the secretion of vascular endothelial growth factor （VEGF） and their abilities of proliferation， migration and tubule formation. Knockdown of GSDMD could reverse the above effects. ConclusionGSDMD-mediated pyroptosis of partial synovial VEC aggravates RA joint destruction through VEGF secretion that promotes proliferation， migration and angiogenesis of the remaining VEC， which may be a new target to block neovascularization and inhibit joint destruction in RA.