Objective To observe the effects of one kind of angiotensin converting enzyme inhibitor (ACE1) drugs fosinopril (FOS) on transforming growth factor β1 (TGF-β1)and β1- integrin( Itg-31 ) expression in rat glomerular mesangial cells (GMC)induced by lipopolysacchatide (LPS).Methods We established the cultured glomerular mesangial cells of rat in vitro and passages 3 ～ 10 of cells were used in the experiment after identification.The experiment included the following groups:Control group,LPS induced group (LPS group) and FOS intervened group.According to the different concentrations of FOS,FOS intervened group was divided into high,middle and low dose FOS groups,which were FOS1 group,FOS2 group and FOS3 group respectively.The changes of TGF-β1 protein secretion was detected by the enzyme-linked immunosorbent-assay; The changes of TGF-β1 and Itg-β1 mRNA expression was detected by quantitative real-time RT-PCR.Results (1) TGF-β1protein secretion in rat GMC at 6h,12h,24h three time points:They were 958.55 ± 34.67 ( ng/L),1052.05 ±48.59( ng/L),1166.06 + 35.39 (ng/L) respectively in Control group.They were 1342.12 + 39.87 ( ng/L),1432.31 + 39.33 (ng/L) and 1 537.77 + 43.79 (ng/L) respectively in LPS group,which were higher significantly than those in Control group ( all P ＜ 0.01 ).They were 779.58 ± 48.64 ( ng/L),878.33 ± 29.50 (ng/L) and 962.57 ±31.94( ng/L) in FOS1 group,989.311±73.56(ng/L),1073.29±66.89(ng/L) and 1210.75 ±61.68(ng/L) in FOS2 group,1 253.78 ±45.32( ng/L),1 348.18 ±45.81 (ng/L) and 1450.06 ±46.24( ng/L) in FOS3 group respectively,which were lower significantly in all FOS intervened groups than that in LPS group (all P＜O.01).(2)TGF-β1 mRNA expressions in rat GMC at6h,12h,24h three time points were higher significantly than that in Control group.TGF-β1 mRNA expressions were lower significantly in all FOS intervened groups than that in LPS group.( 3 ) Itg-β1 mRNA expressiones in rat GMC at 6h,12h,24h three time points were higher significantly than that in Control group.Itg-β1 expressions were lower significantly in all FOS intervened groups than that in LPS group.Conclusions LPS can induce the increase of TGF-β1 secretion and mRNA expression.FOS can inhibit the TGF-β1 secrection and mRNA expession in GMC as dose-dependent manner,at the same time down regulated the Itg-β1 mRNA expression iuduced by LPS.All above supply the theoretical evidence for the renal protection of FOS by non-hemodynamics mechanism.

Abstract: Objective　To investigate the impacts of vaccination with inactivated SARS-COV-2 vaccine on the clinical manifestations and serological responses of COVID-19 patients infected by Delta and Alpha variants. Methods　Clinical and experimental data of 341 confirmed SARS-COV-2 patients were collected from The Eighth Affiliated Hospital of Guangzhou Medical University May 1- September 30, 2021. The subjects were divided into Delta and Alpha variant group according to virus variants, and were divided into vaccinated group and unvaccinated group according to whether they had received inactivated COVID-19 vaccine or not. The clinical manifestations and serological responses of patients with Delta and Alpha variant, and vaccinated and unvaccinated patients with Delta and Alpha variants were compared. Results　Totally 253 patients were infected with Delta variant (103 vaccinated and 150 unvaccinated patients), and 88 patients were infected with Alpha variant (21 vaccinated and 67 unvaccinated patients). The proportion of asymptomatic infection in Delta variants group was significantly lower than that in Alpha variants group (P<0.01). Delta variant group of vaccination rates and vaccine breakthrough infection rate was 40.7% (103/253) and 22.9% (58/253), were higher than Alpha variant group was 23.9% (21/88) and 8.0% (7/88), difference was statistically significant (χ2= 8.009, 9.484, P<0.01). The proportion of cough and fever in Delta variant group was higher than that in Alpha variant group (both P<0.01), the peak viral load was higher than that of Alpha variant group (P<0.01), the virus duration was longer than that of Alpha variant group (P<0.01), the levels of SAA, CRP and IFN were higher than those of Alpha variant group (all P<0.05), CD4+T cell count was lower than that of Alpha variant group (P<0.05), IgG and IgM levels were lower than those of Alpha variant group (both P<0.01). The proportion of moderate COVID-19 in the vaccinated group was lower than that in the unvaccinated group (P<0.01). In these two variants, the peak viral load of vaccinated group was lower than that of the unvaccinated group (both P<0.01), the duration of virus was shorter than that of unvaccinated group (both P<0.01). The levels of SAA, CRP and IL-6 in the vaccinated group were lower than those in the unvaccinated group (all P<0.05), CD4+T cell level was higher than that of unvaccinated group (both P<0.05), IgG and IgM level were higher than those in unvaccinated group (both P<0.05). Conclusions　Delta variant can lead to higher viral load and more severe disease course, which is associated with vaccine breakthrough infection. Inactivated vaccines for COVID-19 can reduce severe illness and death by reducing viral load, disease duration and inflammatory response through humoral and cellular immune mechanisms.

Data quality management system is essential to ensure accurate, complete, consistent, and reliable data collection in clinical research. This paper is devoted to various choices of data quality metrics. They are categorized by study status, e.g. study start up, conduct, and close-out. In each category, metrics for different purposes are listed according to ALCOA+ principles such us completeness, accuracy, timeliness, traceability, etc. Some general quality metrics frequently used are also introduced. This paper contains detail information as much as possible to each metric by providing definition, purpose, evaluation, referenced benchmark, and recommended targets in favor of real practice. It is important that sponsors and data management service providers establish a robust integrated clinical trial data quality management system to ensure sustainable high quality of clinical trial deliverables. It will also support enterprise level of data evaluation and bench marking the quality of data across projects, sponsors, data management service providers by using objective metrics from the real clinical trials. We hope this will be a significant input to accelerate the improvement of clinical trial data quality in the industry.

Objective To observe the efficacy of Mimics finite element analysis software in the gasserian ganglion radiofrequency treatment of trigeminal neuralgia. Methods 180 cases with primary trigeminal neuralgia and VAS score ≥8 were randomly divided into 2 groups (n = 90 each): CT group (group C) and Mimics group (group M). The preoperative skull CT image of the foramen of cranial base could be analyzed in group C. The preoperative cranial CT image could be reconstructed and analyzed by Mimics finite element analysis software in group M. The puncturing success rate, complications rate and the outcomes between two groups were recorded. Results The puncturing success rates were 100% in group M and 92% in group C (P < 0.05). 6 cases with hematoma and 1 case, which were stabbed into the oral cavity were found in group C. No puncture complication was found in group G. There was no statistically significant between the two groups (P < 0.05). The VAS score was 1.6 ± 0.3 in group C and 1.3 ± 0.4 in group G, there was no statistical significance (P > 0.05) between them. Conclusions The Mimics finite element analysis software could improve the success rate of basicranial foramen ovale puncture and reduce the occurrence rate of puncture complications. Therefore , it could be safely applied to the treatment of primary trigeminal neuralgia by gasserian ganglion radio frequency.

Objective To investigate the security and result of operation of one side polycystic kidney removal and homonymy kidney transplantation simultaneously for giga-polycystic kidney di-sease of terminal stage. Methods Forty-five patients with polycystic kidney of transplantation were retrospectively analyzed. The patients were divided into 2 groups. Patients of group A (n=23) under-went resection of the cystic kidney by extraperitoneum and the other 22 patients(group B) didn't re-move the cystic kidney. The data including average length of hospital stay, variance of blood pressure, lessen of abdominal circumference, lung capacity, total lung capacity, FEV1.0/FVC, incidence rate of delayed graft function (DGF) and 1 year patient/kidney survival rate of the 2 groups were compared. Results The average length of post-operative hospital stay of group A was (14.5±2.6)d,lessen of blood pressure was (30.0±0.7/13.34±8.4)mm Hg, lessen of abdominal circumference was (11.0+ 6. 3) cm, lung capacity increased (1.4±0.3)L, total lung capacity increased (2.0±1.0)L, FEV1.0/ FVC increased (5.3±1.0) %, the incidence rate of DGF was 8.7% (2/23), 1 year patient/ kidney survival rate was 100.0%/95.7%. The average length of post-operative hospital stay of group B was (28.45±7.9)d,lessen of blood pressure was (3.9±11.2/2.9±12. 0)ram Hg, lessen of abdominal circumference was (3.3±2.2)cm, lung capacity increased (0.44±0.3)L, total lung capacity increased (0.8±0.2) L, FEV1.0/FVC increased (2.0±0.9)%, the incidence rate of DGF was 9.1%(2/22), 1 year patient/kidney survival rate was 100.0%/95.5%. There were no significant differences of the incidence rate of DGF and 1 year patient/kidney survival rate between the 2 groups. While there were significant differences of the other data between the 2 groups(P＜0.05). Conclusions It is safe and convenient for one side polycystic kidney removal and homonyrny kidney transplantation simultaneous-ly for giga-polycystic kidney disease of terminal stage. The procedure could be applied to the patients of graveness complication or giga-polycystie kidney hampering operation of transplantation.

Objective To investigate the expression profiles of microRNA in early esophageal squamous cancer and normal esophageal tissues and verify the significantly different expression miRNAs , further to study the effects on proliferation of EC109. Methods The microarray assay was performed to analyze miRNA expression profiles in three pairs of early esophageal squamous cancer and the corresponding normal esophageal tissues. Quantitative real-time polymerase chain reaction (qRT-PCR) was used in another 38 pairs samples to further verify the differentially expressed miRNAs . Three verified miRNAs ( miR-29a, miR-221 and miR-222) mimics were transfected into EC109 respectively and CCK8 method was used to study the effect of cell proliferation in each miRNA. Results Microarray technique selected 53 miRNAs that differentially expressed in early esophageal squamous cancer and normal esophageal tissues , 32 miRNAs were up-regulated and 21 miRNAs were down-regulated. qRT-PCR verified that miR-29a was significantly down-regulated (P < 0.05) and miR-221, miR-222 were significantly up-regulated (P < 0.05) in early esophageal squamous cancer tissue. Over-expression of miR-29a could significantly inhibit the proliferation of EC109 (P < 0.05) whereas over-expression of miR-221 or miR-222 could both significantly promote the proliferation of EC109 (P < 0.05). Conclusion There was significant difference of miRNAs expression between early esophageal squamous cancer and normal esophageal tissues, and the differentially expressed miRNAs could be used as new biomarkers for early diagnosis of esophageal squamous cancer.

Objective To investigate the outcomes of patients with rheumatoid arthritis (RA) treated by different combination of synthetic disease modifying antirheumatic drugs (DMARDs) under the guidance of treat-to-target strategy.Methods Forty-two RA patients with high disease activity were enrolled into this randomized,open-label and prospective study.It was comprised of a maximal 36-week induction phase and then followed by a maintenance phase up to 84 weeks.Combination of synthetic DMARDs was initiated in the induction phase,with or without low dose glucocorticoids (GCs) during the first 12 weeks.Patients who achieved low disease activity (LDA) were randomized into two maintenance groups.An increase of DAS28 by 0.6 was defined as relapse.The patients achieved LDA in the induction phase,relapsed during maintenance phase and possible relevant risk factors were analyzed.Results Twenty-seven (64％) patients achieved LDA during the induction phase.More non-smoking patients achieved LDA than those smoked [85％ (11/13) vs 55％(16/29),P＜0.05].During the maintenance phase,14 (61％) out of 27 patients relapsed.Patients taking GCs during the first 12 weeks had a significantly higher relapse rate compared to those without GC (83％ vs 36％,P=0.021).Patients who entered maintenance phase at week 12 had a significantly higher tendency to relapse compared to those who entered the maintenance phase at week 24 [75％(9/12) vs 33％(3/9),P=0.026].Conclusion Smoking seems to be a risk factor for RA patients who fail to reach LDA.Low dose GCs as a bridge therapy may require a longer duration.High relapse rates in both the maintenance groups indicat that a longer tight induction phase may be appropriate before downstairs therapy.

Objective:To verify the fracture risk assessment tool ( FRAX) to estimate the probability of osteoporotic fracture in patients with rheumatoid arthritis ( RA ) with or without bone mineral density (BMD), and identify associated risk factors of osteoporosis .Methods: In the study, 200 patients with rheumatoid arthritis aged more than 40 years in Peking University First Hospital from Dec .2009 to Dec. 2012 were recruited.Clinical information was obtained from a questionnaire of their case history and medical records.FRAX tool was administered.Their lumber spine and left femoral BMD were determined by dual energy X ray absorptiometry.The gender, age, disease duration, menopause status, body mass index ( BMI) and accumulative dose of glucocorticoid were obtained in retrospect .Correlation analysis was conducted between the BMD and clinical information .Results:The study population ( female, 77.5%) had a mean age of 59.4 years, in which 10 (13%) patients showed a normal BMD, 67 (87%) were osteopenia or osteoporosis , while 32 patients (16%) had fragile fracture.Compared with the patients with normal BMD, the subjects with low BMD had significantly older age , longer period for corticoids usage , higher day dose and accumulated dose of corticoids .The 10-year fracture risk of sustai-ning major osteoporotic fractures and hip fracture was higher .No significant difference was observed be-tween the 10-year fracture risks calculated with BMD and without BMD .The values of the different area under the receiver operating characteristic ( ROC) curve ( AUC) for major and hip fractures calculated in three ways:without BMD, with the femoral neck BMD, and with T-score.The best result was for FRAX tool for hip fracture with the T-score ( AUC 0 .899 ) .A stepwise multivariate linear regression model was constructed to explore the relationship between the different clinical factors studied and a low BMD . Three statistically significant variables for lumber BMD were pain on visual assessment scale ( VAS ) (P=0.02), fracture history (P=0.003) and a higher steroid accumulated dose (P=0.008).Three statistically significant variables for left hip BMD were age (P<0.001), fracture history (P=0.05) and lower BMI ( P=0.03) .Conclusion:Low BMD is a common complication in RA patients .Risk factors for major fracture and hip fracture are increased .There is a positive correlation between FRAX calculated with and without BMD or T score .FRAX with the femoral neck T score or BMD presents a discriminatory capacity better than FRAX without BMD , according to the AUC ROC .

Objective To investigate the ultrastructure and function changes of the thyroid parafollicular cell in ANP rats and to study the possible mechanism of hypocalcemia during ANP.Methods Thirty-two male Wistar rats were randomly divided into 4 groups:sham operation group ( SO group) and ANP 3,6,12 h groups.ANP model was induced by retrograde injection of 5％ sodium taurocholate into the biliopancreatic duct. The serum levels of amylase,lipoidase,calcitonin and Ca2+ were measured.The pathological changes in pancreatic tissue were observed.The ultrastructure changes of thyroid parafollicular cell were observed.ResultsThe serum levels of amylase,lipoidase,calcitonin and Ca2+ were (4025 ±579)U/L,(8272 ± 794) U/L,(383.6 ± 64.5) pg/ml,(2.41 ± 0.12) mmol/L at 6h in ANP group,which were significantly higher than those in SO group [ ( 1063 ± 129 ) U/L,( 55 ± 18 ) U/L,( 143.1 ± 42.2 ) pg/ml,(2.97 ±0.12 ) mmol/L ( P ＜0.05 ) ].Under the electron-microscopy,the nucleus of thyroid parafollicular cells shrinked and mitochondrial proliferation and endoplasmic reticulum fusion appeared.After 6 h,all the organelle reduced and disappeared,and only small amount of secretory granules remained.Conclusions Changes in the structure and function of the thyroid parafollicular cells occur in rats of ANP,and they induce the development of hypocalcemia.

Objective To observe the effects of fosinopril(FOS)on secretion of ColⅠ,expression of Smad2、Smad7 mRNA in TGF-β1-induced glomerulomesangial cells(GMC)in rat model. Methods Rat glomerular mesangial cells were cultured in vitro,passages 3 - 10 cells were used in the study after identification,and the cells were divided into 3 groups:control group(Ctrl group),TGF-β1 group,and fosinopril group. Expression of Col Ⅰ in cell culture supernatant was detected by the enzyme-linked immunosorbent assay(ELISA)at 6 h,24 h and 48 h. Changes of Smad2,Smad7 mRNA expression were evaluated by fluorescent quantitation PCR. Results Glomerular mesangial cells had Col Ⅰ protein expression. Secretion of Col Ⅰ was significantly higher in TGF-β1 group than those in Ctrl group at each time point(P ＜ 0.01),however the Col Ⅰ was significantly lower in fosinopril group at all time points than that in TGF-β1 groups(P ＜ 0.05). Glomerular mesangial cells also had Smad2,Smad7 mRNA expressions. The expressions of Smad2,Smad7 mRNA were significantly higher in TGF-β1 group than those in Ctrl group at each time point. Expression of Smad2 mRNA was significantly lower in fosinopril group than that in TGF-β1 group at all time points,while the difference in Smad7 mRNA expression between TGF-β1 group and fosinopril group showed no statistical significance(P ＞ 0.05). Conclusions Fosinopril could inhibit the secretion of Col Ⅰ and expression of Smad2 mRNA in glomerular mesangial cells induced by TGF-β1,suggesting that fosinopril might delay glomerular sclerosis through inhibiting the expression of Smad2 in TGF-β1/Smad signaling pathway.