Pharmacovigilance impact research(PIR),as an important application field of pharmacoepidemiology,has attracted continuous attention in recent years from drug regulatory authorities,pharmaceutical manufacturers,and the academic community both domestically and internationally.This paper provides an interpretation of PIR based on the Guide for Methodology in Pharmacoepidemiologic Research(2nd edition).First,an overview of the implications of PIR will be provided,focusing on the pathways of pharmacovigilance activities and the significant importance of conducting PIR.Second,it reviews commonly used study designs and presents illustrative case examples.Building on this,the specific statistical considerations relevant to PIR were discussed.Finally,the challenges and prospects of conducting pharmacovigilance impact studies in a scientific and standardized manner are summarized.Compared with the previous edition,the 2nd edition has expanded the application scenarios of pharmacoepidemiology to include new areas such as PIR.Drawing on the guideline content and practical experience,this paper provides a detailed introduction and case analysis of PIR,serving as a reference for researchers engaged in this field.

Pharmacovigilance impact research(PIR),as an important application field of pharmacoepidemiology,has attracted continuous attention in recent years from drug regulatory authorities,pharmaceutical manufacturers,and the academic community both domestically and internationally.This paper provides an interpretation of PIR based on the Guide for Methodology in Pharmacoepidemiologic Research(2nd edition).First,an overview of the implications of PIR will be provided,focusing on the pathways of pharmacovigilance activities and the significant importance of conducting PIR.Second,it reviews commonly used study designs and presents illustrative case examples.Building on this,the specific statistical considerations relevant to PIR were discussed.Finally,the challenges and prospects of conducting pharmacovigilance impact studies in a scientific and standardized manner are summarized.Compared with the previous edition,the 2nd edition has expanded the application scenarios of pharmacoepidemiology to include new areas such as PIR.Drawing on the guideline content and practical experience,this paper provides a detailed introduction and case analysis of PIR,serving as a reference for researchers engaged in this field.

Objective To enhance the mechanical properties of trichiral honeycomb sandwich structures and satisfy the design criteria for vertebral implant structures.Methods A chiral-like honeycomb sandwich structure with an auxiliary support structure was constructed for optimal design.The finite element method was used to study the influence of the auxiliary support structure on the chiral-like honeycomb sandwich structure and the relationship between the support position and mechanical property parameters.Furthermore,the influence of the deformation mechanism of different structures on mechanical properties was discussed.Results All chiral-like honeycomb sandwich structures exhibited enhanced mechanical properties in comparison to trichiral honeycomb sandwich structures.The mechanical properties of the chiral-like dCW honeycomb sandwich structure with the auxiliary support structure positioned perpendicular to the ligament were optimal,and this position represented the optimal support position.When the volume was used as a control variable,the compressive stiffness,stiffness-to-mass ratio,and transverse strain of the chiral-like honeycomb sandwich structure in the x1 direction were significantly correlated with the change of the support position,and all of them were positively correlated.Conclusions As a novel chiral-like honeycomb structure,it provides a biomechanical basis for the optimal design and clinical application of honeycomb sandwich structures as vertebral implant structures.

Objective To enhance the mechanical properties of trichiral honeycomb sandwich structures and satisfy the design criteria for vertebral implant structures.Methods A chiral-like honeycomb sandwich structure with an auxiliary support structure was constructed for optimal design.The finite element method was used to study the influence of the auxiliary support structure on the chiral-like honeycomb sandwich structure and the relationship between the support position and mechanical property parameters.Furthermore,the influence of the deformation mechanism of different structures on mechanical properties was discussed.Results All chiral-like honeycomb sandwich structures exhibited enhanced mechanical properties in comparison to trichiral honeycomb sandwich structures.The mechanical properties of the chiral-like dCW honeycomb sandwich structure with the auxiliary support structure positioned perpendicular to the ligament were optimal,and this position represented the optimal support position.When the volume was used as a control variable,the compressive stiffness,stiffness-to-mass ratio,and transverse strain of the chiral-like honeycomb sandwich structure in the x1 direction were significantly correlated with the change of the support position,and all of them were positively correlated.Conclusions As a novel chiral-like honeycomb structure,it provides a biomechanical basis for the optimal design and clinical application of honeycomb sandwich structures as vertebral implant structures.

Objective:Bioinformatics was used to analyze the gene expression profile of renal chromophobe cell carcinoma (RCCC) to find out the key genes of RCCC.Methods:Chromophobe renal cell carcinoma gene chip data GSE15641 and GSE11151 were downloaded from the GEO database. Using R software packages such as " Affy" and " limma" in R software to screen differentially expressed genes, combining with David and STRING online bioinformatics tools to analyze the regulatory network of differentially expressed genes and construct protein-protein interaction (PPI) network, the Hub gene was screened through the Cytohubba plug-in of Cytoscape software.Results:A total of 261 differentially expressed genes were screened, including 194 down-regulated genes and 67 up-regulated genes. Gene enrichment (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to explore their biological functions. In GO enrichment analysis, biological processes were mainly enriched in cell secretion, gluconeogenesis and cell proliferation regulation; in cell composition, they were mainly enriched in exosomes, plasma membranes and their components; in molecular function, they were mainly enriched in heparin binding; in KEGG pathway analysis, they were mainly enriched in metabolic pathway, antibody biosynthesis pathway and renin angiotensin system pathway. PPI network was constructed by using online bioinformatics tools. The top 10 Hub genes were screened by using cytohubba plug-in in Cytoscape software, which were pipecolic acid and sarcosine oxidase (PIPOX), hydroxyacid oxidase 2 (HAO2), kynurenine 3-monooxygenase (KMO), solute carrier family 2 member 2 (SLC2A2), formimidoyltransferase cyclodeaminase (FTCD), angiogenin (ANG), APOBEC1 complementation factor (A1CF), aldehyde dehydrogenase 8 family member A1 (ALDH8A1), vitamin D binding protein (GC), histidine rich glycoprotein (HRG).Conclusions:Bioinformatics analysis of differentially expressed genes in renal chromophobe cell carcinoma can effectively explore the interaction information of these differentially expressed genes, and provide new ideas for the treatment of renal chromophobe cell carcinoma.

Objective:To explore the application value of enhanced recovery after surgery (ERAS) in laparoscopic radical resection of bladder cancer and ileal bladder surgery under modular operation procedures.Methods:A retrospective selection of 42 cases of laparoscopic radical radical resection of bladder cancer and ileal bladder surgery performed by the Department of Urology, General Hospital of Southern Theater Command from January 2017 to December 2019 were divided into two groups according to the different management methods adopted during the perioperative period: ERAS management group and conventional management group, each with 21 cases. Among them, patients in the ERAS management group were managed by ERAS during the perioperative period, and patients in the conventional management group were managed by conventional management during the perioperative period. The postoperative hospital stay, first exhaust time, first defecation time, first time to get out of bed, first liquid food time, postoperative visual analogue scale (VAS) score, as well as transferrin, upper arm circumference, body mass index, plasma albumin, total protein, and total protein were compared between the two groups of patients after surgery. The measurement data conforming to the normal distribution were expressed as mean±standard deviation ( Mean± SD), and the in dependent t-test was used for comparison between groups; the measurement data of non-normal distribution were expressed as the median (interquartile range) [ M( P25, P75)], the independent sample Mann-Whitney U test was used for comparison between groups; the Chi-square test was used for comparison of enumeration data between groups. Results:The postoperative hospital stay in the ERAS group was (8.9±1.8) d, the first exhaust time was (33.4±3.2) h, the first defecation time was (60.3±7.8) h, the first time to get out of bed was (23.1±6.7) h, the first liquid food time was (82.7±18.5) h and postoperative VAS was (1.3±0.6), that were significantly reduced compared with the conventional treatment group [(12.3±2.3) d, (51.4±5.2) h, (73.0±8.1) h, (34.7±8.2) h, (109.7±21.6) h, (3.6±0.8)], the difference were statistically significant ( P<0.05). In the ERAS group, the decreased value of transferrin was [0.8 (-0.4, 2.2) g/L], the decreased value of body mass index was[1.61±0.73], the decreased value of plasma albumin was [3.5±1.5 g/L], the decrease value of total protein was[10.1±5.6 g/L] and the decrease value of prealbumin was [90.5±11.3 mg/L] were significantly lower than those of the conventional management group[(1.9(0.9, 3.6) g/L, (2.32±1.05) kg/m 2, (9.6±2.0) g/L, (16.3±4.9) g/L, (131.3±7.4) g/L], and the difference were statistically significant ( P<0.05). Conclusion:Modular laparoscopic precision resection of bladder cancer and ERAS concept after ileal bladder surgery is beneficial to shorten the hospital stay, reduce postoperative pain, have less impact on the patient′s body loss and immune function, and can speed up the patient′s postoperative recovery.

Objective:To determine the efficacy and safety of sacral neuromodulation (SNM) in incomplete spinal cord injured (SCI) subjects affected by neurogenic lower urinary tract symptoms.Methods:Clinical data of 36 patients with incomplete spinal cord injury who underwent SNM from February 2015 to April 2019 were retrospectively analyzed and were divided into group NUR (16 cases neurogenic urinary retention group) and group NOAB (20 cases of neurogenic bladder overactive group). If at least 50% clinical improvement occurred, the patient would undergo a permanent SNM procedure. The patients were evaluated by using bladder diary, postvoid residual volume measurement, frequency of clean catheterization and urodynamic parameters before and during the test, and after the permanent SNM.Results:Among the 36 patients, 21 cases (58.3%) were tested effectively and received permanent stimulator implantation, 7(19.4%) in NUR group and 14(38.9%) in NOAB group. The residual urine volume of bladder, the average number of catheterization and the average number of urination in NUR group were improved in different degrees. After operation, the symptoms of frequent urination, urgency of urination and incontinence in NOAB group were relieved to varying degrees. During the follow-up, 2 patients with urinary retention failed the treatment. After the Ⅰ phase of the contralateral S3, the curative effect was recovered. A patient were infected after operation, and the wound healed after removal of the infection.Conclusions:The SNM is safe and effective in the treatment of neurogenic lower urinary tract symptoms in some incomplete spinal cord injury patients, and is helpful to protect renal function in patients with spinal cord injury. SNM can not improve all symptoms at times, but the SNM can be considered in patients with ineffective or intolerant traditional treatment.

Objective: To investigate the effects of modified three-step procedure for anatrophic nephrolithotomy in the treatment of complex staghorn renal calculi. Methods: A total of 22 patients with complex staghorn renal calculi between June 2013 and June 2016 at Department of Urology in Guangzhou General Hospital of Guangzhou Military Command were retrospective analyzed. There were 13 males and 9 females, ranging from 35 to 62 years old with mean age of 47 years. There were 17 patients with dull pain, and 5 patients who were found through physical examinations. Kidney calculi located in left kidney in 15 patients, right kidney in 7 patients. All patients were treated with modified three-step procedure for anatrophic nephrolithotomy. The operation time, blood loss, time of intraoperative renal ischemia, and postoperative complications were recorded. Serum creatinine (Scr), blood urea nitrogen(BUN), β₂-microglobulin(β₂-MG), diseased side glomerular filtration rate(GFR) , and renal cortical thickness of the diseased kidney in preoperative and postoperative were compared. The clinical data were compared by paired sample t test between pre-operation and post-operation. Results: The calculi were completely removed in 22 patients, the mean operation time was 84 minutes (50 to 126 minutes), the mean time of intraoperative renal ischemia was 31 minutes (20 to 56 minutes), the mean blood loss was 246 ml (150 to 360 ml). There were no secondary bleeding or urinary fistula happened, the perinephric drainage tub was removed in 3 to 7 days postoperative, the mean hospitalization time was 7 days.Compared with the preoperative, the Scr ((172.7±21.3)μmol/L vs. (146.4±22.8)μmol/L, t=7.197, P=0.000), BUN ((9.2±1.8)mmol/L vs. (8.0±0.5)mmol/L, t=3.798, P=0.001) and β₂-MG ((203.0±32.0)μg/L vs. (175.6±23.8)μg/L, t=5.009, P=0.000) in postoperative decreased, the diseased side GFR increased ((28.6±4.0) ml/min比(31.8±3.3) ml/min, t=-3.521, P=0.002). There were no significant difference of diseased renal cortical thickness between preoperative and postoperative(t=-1.323, P=0.200). There were 12 patients with postoperative pain, 2 patients with vomiting, 3 patients with fever, and 2 patients with wound infection. The follow-up time was 6 months, no residual stones in 22 patients. Conclusion The modified three-step procedure for anatrophic nephrolithotomy has high stone free rates with less effects on renal function and fewer complications, the method could be widely applied.

Objective To investigate the effect of microRNA-497 (miR-497) on cell proliferation and apoptosis capability of baldder cancer cell line EJ. Methods EJ human baldder cancer cells were divided into miR-497 mimics group,mimics NC group,miR-497 inhibitor group and inhibitor NC group. MiR-497 mimics,mimics NC,miR-497 inhibitor and inhibitor NC were transfected into EJ cells by LipfectamineTM 2000. The transfection effi-ciency was observed under a fluorescence microscope 6 hours after. And qRT-PCR was used to detected the expres-sion of miR-49748 hours after. Plate clone formation assay ,MTT assay and flow-cytometric analysis of apoptosis were used to detect the cell proliferation and apoptosis of bladder cancer EJ cells. Western blot was employed to de-termine the protein expressions of bcl-2 and caspase-3. Results Under fluorescence microscope ,the efficiency rate of four groups were over 90%. And qRT-PCR results showed miR-497 expression in EJ cells increased signifi-cantly in miR-497 mimics group than those in the control group(P<0.01),while miR-497 inhibitor post expres-sion decreased(P<0.01). Overexpression of miR-497 significantly suppressed EJ cells proliferation(P<0.01), and prompted EJ cells apoptosis(P < 0.01)compared with the control group. Moreover ,opposite results were ob-tained when miR-497 inhibitor was transfected into EJ cells . Compared with negative control ,the protein expres-sion of Bcl-2 down-regulated(P < 0.01)and Caspase-3 up-regulated(P < 0.01)in miR-497 mimics transfection group. Conclusions MiR-497 could suppress the proliferation and promote apoptosis of EJ cells ,which might be related to the protein expression of Bcl-2 and Caspase-3.

A s an im portant part of epigenetic m arker, D N A m ethylation involves in the gene regulation and attracts a w ide spread attention in biological auxology, geratology and oncology fields. In forensic science, because of the relative stable, heritable, abundant, and age-related characteristics, D N A m ethyla-tion is considered to be a useful com plem ent to the classic genetic m arkers for age-prediction, tissue-identification, and m onozygotic tw ins' discrim ination. V arious m ethods for D N A m ethylation detection have been validated based on m ethylation sensitive restriction endonuclease, bisulfite m odification and m ethylation-C pG binding protein. In recent years, it is reported that the third generation sequencing m ethod can be used to detect D N A m ethylation. T his paper aim s to m ake a review on the detection m ethod of D N A m ethylation and its applications in forensic science.