OBJECTIVE To establish a method for determining the contents of clopidogrel （CLP）， clopidogrel carboxylate （CLP-C）， clopidogrel acyl-β-D-glucuronide （CLP-G） and contents of clopidogrel active metabolite （CAM） in rat plasma， and to investigate their in vivo pharmacokinetic characteristics. METHODS The Shisedo CAPCELL ADME column was used with a mobile phase consisting of water and acetonitrile （both containing 0.1% formic acid） in a gradient elution. The flow rate was 0.4 mL/min， and the column temperature was maintained at 20 ℃. The injection volume was 2 μL. The analysis was performed in positive ion mode using electrospray ionization with multiple reaction monitoring. The ion pairs for quantitative analysis were m/z 322.1→211.9 （for CLP）， m/z 308.1→197.9 （for CLP-C）， m/z 322.1→154.8 （for CLP-G）， m/z 504.1→154.9 [for racemic CAM derivative （CAMD）]. Six rats were administered a single intragastric dose of CLP （10 mg/kg）. Blood samples were collected before medication and at 0.08， 0.33， 0.66， 1， 2， 4， 6， 10， 23 and 35 hours after medication. The established method was used to detect the serum contents of various components in rats. Pharmacokinetic parameters were then calculated using WinNonlin 6.1 software. RESULTS The linear ranges for CLP， CLP-C and CAMD were 0.08-20.00， 205.00-8 000.00， and 0.04-25.00 ng/mL， respectively （r≥0.990）. The relative standard deviations for both intra-day and inter-day precision tests were all less than 15%， and the relative errors for accuracy ranged from －11.68% to 14.40%. The coefficients of variation for the matrix factors were all less than 15%， meeting the requirements for bioanalytical method validation. The results of the pharmacokinetic study revealed that， following a single intagastric administration of CLP in rats， the exposure to the parent CLP in plasma was extremely low. Both the area under the drug concentration-time curve （AUC0-35 h） and the peak concentration of the parent CLP were lower than those of its metabolites. The AUC0-35 h of the active metabolite CAM was approximately 43 times that of CLP， though it had a shorter half-life （2.53 h）. The inactive metabolite CLP-C exhibited the highest exposure level， but it reached its peak concentration the latest and was eliminated slowly. The AUC0-35 h of CLP-G was about four times that of CAM， and its half-life was similar to that of CLP-C. CONCLUSIONS This study successfully established an liquid chromatography-tandem mass spectrometry method for the determination of CLP and its three metabolites， and revealed their pharmacokinetic characteristics in rats. Specifically， the parent drug CLP was rapidly eliminated， while the inactive metabolites CLP-C and CLP-G exhibited long half-lives， and active metabolite CAM displayed a transient exposure pattern.

Objective To analyze the correlation between thromboelastogram indicators(R time,K time,MA value)and global registry of acute coronary events(GRACE)score and acute myocardial infarction(AMI),and explore the risk factors for the onset of AMI.Methods A total of 108 patients with AMI who were hospitalized in Xuancheng Central Hospital for the first time from September 2020 to February 2023 were selected as the observation group,while 70 patients with stable coronary heart disease were selected as the control group.The clinical basic data,thromboelastogram indicators,GRACE score,and homocysteine(Hcy)of all study subjects were collected.The differences of clinical basic data,thromboelastogram indica-tors,GEACE score,and Hcy level between the observation group and the control group were statistically ana-lyzed.The predictive value of thromboelastogram indicators,GRACE score,and Hcy level for the occurrence of AMI was evaluated by using the receiver operating characteristic(ROC)curve.Binary Logistic regression model was used to conduct univariate and multivariate regression analyses on indicators with statistically sig-nificant differences,in order to determine the independent risk factors for AMI occurrence.Results There were significant differences of R time,K time,MA value,GRACE score,serum Hcy level,and the proportion of underlying diseases between the observation group and the control group(P＜0.05).The ROC curve re-sults showed that R time,K time,MA value,GRACE score,and Hcy had good predictive value for the occur-rence of different types of AMI,and the value of the combined application was higher.Univariate Logistic re-gression showed that MA value,GRACE score,Hcy level,and underlying disease were positively correlated with the occurrence of AMI(P＜0.05),while R time and K time were negatively correlated with the occur-rence of AMI(P＜0.05).Multivariate Logistic regression showed that high GRACE score and elevated Hcy level were independent risk factors for the occurrence of AMI(P＜0.05),while R time and K time were inde-pendent protective factors for the occurrence of AMI(P＜0.05).Conclusion Thromboelastogram,Hcy,and GRACE score could be used as dynamic monitoring indicators for clinical risk assessment of AMI in acute cor-onary syndrome population.

Objective:To analyze the changes of diagnosis and treatment before and after renal biopsy in adult patients with acute kidney disease (AKD), and to explore the value of renal biopsy in the diagnosis and treatment of AKD.Methods:It was a single-center retrospective observational study. The adult patients with AKD who underwent renal biopsy in the Department of Nephrology of the First Affiliated Hospital of Nanjing Medical University from January 1, 2017 to December 31, 2021 were enrolled. Demographic data, general clinical data, laboratory tests, and diagnosis and treatment data before and after renal biopsy were collected to analyze the concordance rate between clinical and pathological diagnoses, changes in treatment after renal biopsy, and bleeding complication.Results:A total of 575 patients diagnosed with AKD by renal biopsy were included in this study, with age of 51 (36, 63) years old and 359 males (62.4%). Among them, there were 293 patients (51.0%) of acute kidney injury, 348 patients (60.5%) of hypertension and 124 patients (21.6%) of diabetes. The peak serum creatinine was 272 (190, 477) μmol/L. The hemoglobin was 106 (86, 126) g/L. The 24-hour urine protein was 2.15 (0.79, 4.82) g. There were 347 patients (60.3%) of acute glomerular diseases, 136 patients (23.7%) of acute interstitial nephritis, 47 patients (8.2%) of thrombotic microangiopathy, and 45 patients (7.8%) of acute tubular necrosis. The most common types of acute glomerular diseases were IgA nephropathy and anti-neutrophil cytoplasmic antibody-associated glomerulonephritis, accounting for 22.3% (128/575) and 12.2% (70/575), respectively. The clinical diagnoses before renal biopsy were consistent with the renal histopathological diagnoses in 454 patients, with an accuracy rate of 79.0%. Following the renal biopsy, the treatment plan involving glucocorticoids or immunosuppressants was adjusted in 394 patients (68.5%). Significant post-biopsy bleeding occurred in 15 patients (2.6%), with 12 patients requiring blood transfusion and 1 patient requiring surgical intervention.Conclusions:Twenty-one clinical diagnoses do not match the pathological diagnoses in adult AKD patients, 68.5% of patients have changes in their treatment plans, and 2.6% of patients have significant hemorrhagic complications after renal biopsy. Clinicians need to carefully consider the benefits and risks and make individualized decisions about renal biopsy.

Objective To investigate the current situation of achievement transformation in tertiary medical hospitals in Shanghai and propose countermeasures for the existing problems to enhance the effectiveness of achievement transformation.Methods A questionnaire survey was done on the transformation and management of scientific research achievements in 47 terti-ary hospitals in Shanghai.Meanwhile,interviews were carried out among the managers and researchers from these hospitals.Re-sults In the past three years,the rate of transformation achievements in the hospitals was only 2.8%.In the achievement trans-formation existed such problems as weak awareness of scientific researchers,low patent quality,lack of full-time managers,and inflexible management mode.It was also believed that there is a need to improve main responsibilities,achievement management,system establishment,personnel training,resource sharing,department coordination and other related aspects.Conclusion The rate of achievement transformation in tertiary medical institutions in Shanghai is at a lower level.There are numerous problems and difficulties in the transformation.Therefore,urgent efficient countermeasures are needed to promote the transformation of a-chievement.

Objective:To evaluate the effect of preemptive analgesia with ibuprofen on postoperative pain following single posterior tooth implantation, aiming to provide a clinical reference for its application.Methods:A multicenter, randomized, double-blind, placebo-controlled parallel-group trial was conducted. A total of 82 participants were included in the trial, meeting the eligibility criteria from April 2022 to April 2024 at the Capital Medical University School of Stomatology (40 cases), Beijing TianTan Hospital, Capital Medical University (22 cases), Beijing Chao-Yang Hospital, Capital Medical University (20 cases). Participants were randomly assigned in a 1∶1 ratio to either the ibuprofen group or the control group, with each group comprising 41 individuals. Participants in the ibuprofen group received 300 mg of sustained-release ibuprofen capsules orally 15 min before surgery, while the control group received a placebo. Both groups received the same postoperative analgesic regimen for 3 days. Pain scores were assessed using the numerical rating scale at 30 min, 4 h, 6 h, 8 h, 24 h, 48 h, and 72 h postoperatively, and the additional use of analgesic medication was recorded from days 4 to 6 postoperatively.Results:A total of 82 participants were initially enrolled in the study, with 7 dropouts (4 from the control group and 3 from the ibuprofen group), resulting in 75 participants (37 in the control group and 38 in the ibuprofen group) completing the trial. There were no reports of adverse events such as nausea or vomiting among the participants. The ibuprofen group exhibited significantly lower pain scores at 4 h, 6 h and 8 h [1.0 (0.0, 2.0), 1.0 (0.0, 2.0), 1.5 (0.0, 3.0) ] postoperatively compared to the control group 4 h, 6 h and 8 h [2.0 (1.0, 3.0), 3.0 (1.5, 4.0), 2.0 (1.0, 4.0)] ( Z=-1.99, P=0.047; Z=-3.01, P=0.003; Z=-2.10, P=0.036). The proportions of patients requiring additional analgesic medication between days 4 and 6 post-surgery were 18.4% (7/38) in the ibuprofen group and 27.0% (10/37) in the control group, with no significant difference (χ 2=0.79, P=0.373). The median additional medication usage postoperatively was [0.0 (0.0, 0.0) pills] in the ibuprofen group and [0.0 (0.0, 1.0) pills] in the control group, with no significant difference ( Z=-0.78, P=0.439). Conclusions:Preemptive analgesia with ibuprofen effectively reduces postoperative pain following tooth implantation, representing a safe and effective perioperative pain management strategy.

Objective To investigate the therapeutic effect and underlying mechanism of Qishishenshu Capsule on renal fibrosis in mice with early diabetic nephropathy(DN).Methods A DN mouse model was established by multiple injections of streptozotocin.The mice were randomly divided into a normal group(NC),model group(DN),and Qishi group(QS)(0.9 g/(kg·d)),with eight mice in each group.Mice were gavaged continuously for 4 weeks,and fasting blood glucose(FBG)was measured weekly.Four weeks later,urinary albumin/creatinine(UACR),serum creatinine,and blood urea nitrogen were measured.Hematoxylin-eosin,periodicacid-Schiff,and Sirius red staining were used to analyze renal pathological changes.Real-time fluorescence quantitative reverse-transcription polymerase chain reaction was used to detect the mRNA levels of fibronectin(FN),collagen type Ⅰ alpha 1(Col1a1),and α-smooth muscle actin(α-SMA).Immunohistochemistry and Western blot were performed to detect FN,collagen type Ⅰ(Collagen Ⅰ),collagen typeⅢ(Collagen Ⅲ),α-SMA,Podocin,Nephrin,and transforming growth factor-β1/SMAD family member2/3(TGF-β1/Smad2/3)pathway-related proteins.Results Compared with mice in the NC group,those in the DN group showed significantly higher levels of FBG and UACR(P＜0.001),and mesangial hyperplasia,basement membrane thickening,and collagen deposition in the renal tissue.The mRNA levels of FN,Col1a1,and α-SMA were increased(P＜0.05).Protein levels of Podocin and Nephrin were decreased(P＜0.05).The levels of FN,Collagen I,Collagen Ⅲ,α-SMA,and TGF-β1/Smad2/3 pathway proteins were increased(P＜0.05).Compared with the DN group,the QS group's level of UACR was decreased(P＜0.05),their renal pathological injury was alleviated,and mRNA levels of FN,Collagen Ⅰ,andα-SMA were attenuated(P＜0.05);whereas their protein levels of Podocin and Nephrin were elevated(P＜0.05).The levels of FN,Collagen Ⅰ,Collagen Ⅲ,α-SMA,and TGF-β1/Smad2/3 pathway proteins were also decreased(P＜0.05).Conclusions Qishishenshu Capsule improved renal fibrosis in DN mice,probably through the inhibition of the TGF-β1/Smad2/3 signaling pathway.

Objective:To investigate the correlation between complement C3 and urine protein level and proteinuria remission status in patients with primary membranous nephropathy (PMN), and better guide individualized clinical treatment.Methods:It was a single-center retrospective study. The clinical data of PMN patients who underwent renal biopsy in the First Affiliated Hospital of Nanjing Medical University from January 2017 to June 2022 were collected. Patients with 24 h urinary protein ≥ 3.5 g were followed up after receiving standard treatment, and the last outpatient or inpatient review was used as the end point of follow-up. 24 h urine protein was collected to evaluate the remission status of proteinuria. Kaplan-Meier method was used to analyze the correlation between serum and renal complements and proteinuria remission. Cox regression analysis method was used to analyze the correlation between serum C3 level and renal tissue C3 deposition and proteinuria remission.Results:This study included 507 PMN patients with 312 (61.54%) males, aged 54 (43, 64) years old. Compared with 24 h urinary protein < 3.5 g group, proportion of males ( χ2=22.479, P<0.001), age ( Z=-2.521, P=0.012), systolic blood pressure ( Z=-4.148, P<0.001), diastolic blood pressure ( Z=-4.084, P<0.001), serum anti-phospholipase A2 receptor (PLA2R) antibody titer ( Z=-7.019, P<0.001), total cholesterol ( Z=-8.796, P<0.001), triglyceride ( Z=-6.158, P<0.001), low density lipoprotein cholesterol ( Z=-8.716, P<0.001), serum creatinine ( Z=-7.368, P<0.001), serum C3 ( Z=-3.663, P<0.001), serum C4 ( Z=-6.560, P<0.001), proportion of glucocorticoid use ( χ2=116.417, P<0.001) and proportion of immunosuppressant use ( χ2=53.839, P<0.001) were all higher, while serum albumin ( Z=12.518, P<0.001), estimated glomerular filtration rate ( Z=6.345, P<0.001) and serum IgG ( Z=7.321, P<0.001) were all lower in 24 h urinary protein ≥3.5 g group. There were 268 patients included in the follow-up cohort with baseline 24 h urinary protein of 7.15 (5.14, 10.24) g, serum anti-PLA2R antibody titer of 61.44 (14.35, 193.24) RU/ml, serum C3 of 1.005 (0.864, 1.150) g/L, and serum C4 of 0.260 (0.214, 0.317) g/L. Kaplan-Meier survival curve showed that the incomplete remission rate of proteinuria in serum C3 > 1.005 g/L group was lower than that in serum C3 ≤ 1.005 g/L group (log-rank χ2=4.757, P=0.029). There was no significant difference in the incomplete remission rate of proteinuria between serum C4 ≤ 0.260 g/L group and serum C4 > 0.260 g/L group (log-rank χ2=3.543, P=0.060). Renal C1q (log-rank χ2=0.167, P=0.683) and C4 (log-rank χ2=1.927, P=0.165) deposition had no significant effects on proteinuria remission in PMN patients. The incomplete remission rate of proteinuria in patients with renal C3 deposition was higher than that in patients without renal C3 deposition (log-rank χ2=7.018, P=0.008). Univariate Cox regression analysis showed that serum C3 level and C3 deposition in renal tissues were influencing factors of incomplete remission of proteinuria (both P<0.05), while adjusting for gender, age, mean arterial pressure, serum anti-PLA2R antibody, serum albumin and 24 h urinary protein, serum C3 ≤ 1.005 g/L ( HR=1.374, 95% CI 1.021-1.849, P=0.036), C3 deposition in renal tissues ( HR=1.949, 95% CI 1.098-3.460, P=0.023), and serum C3 ≤ 1.005 g/L combined with C3 deposition in renal tissues ( HR=1.472, 95% CI 1.093-1.983, P=0.011) were independent influencing factors of incomplete remission of proteinuria. Conclusions:The serum C3 level and C3 deposition in renal tissues are closely related to urinary protein level and proteinuria remission status in PMN patients. The patients with higher urinary protein have higher serum C3. For patients with massive proteinuria, serum C3 ≤ 1.005 g/L, C3 deposition in renal tissues, serum C3 ≤ 1.005 g/L combined with C3 deposition in renal tissues are independent risk factors of incomplete remission of proteinuria.

Objective To extract and summarize the best evidence of manual rehabilitation therapy in patients with breast cancer related lymphedema.It aims to provide evidence-based basis for clinical nursing staff interven-tion.Methods According to the"6S evidence resource pyramid model",we systematically retrieved from UpTo-Date,BMJ best clinical practice,JBI evidence-based medicine center database of Joanna Briggs Institute in Australi-a,Embase,Cochrane Library,Pubmed,GIN,New Zealand Guidelines collaboration group,SIGN,American Cancer So-ciety,American Association for Physical Therapy,American Society for Lymphatic,American Lymphedema Website,Ontario Association of Registered Nurses of Canada,Yimaitong,CNKI,VIP,CBM,WanFang,CHINAL,Web of Science and OVID databases from establishment of database to January 2023.It mainly includes guidelines,consensuses,evi-dence summaries,clinical decision-making,systematic evaluation and primitive research.There were 2 researchers who independently evaluated the quality of the literature and extracted evidence.Results A total of 19 pieces of the literature were involved,including 4 guidelines,4 consensuses,3 system reviews,1 recommended practice,2 clinical decision-making,1 summary of evidence,4 primitive research.Finally,26 pieces of best evidence are summarized from the 5 aspects of indications,contraindications,treatment points,treatment effects and precautions of manual re-habilitation.Conclusion This study summarized the evidence of manual rehabilitation therapy in breast cancer re-lated lymphedema.It can provide practical basis for clinical nursing staff.In clinical practice,it is important to strictly evaluate whether patients have contraindications to treatment,to follow the recommended treatment plan and monitor complications during treatment.

Objective:To investigate the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with maintenance hemodialysis (MHD) in Jiangsu province during SARS-CoV-2 pandemic in China from December 7, 2022 to January 27, 2023, and to analyze the influencing factors of all-cause death.Methods:It was a multi-center cross-sectional investigation. Structured questionnaire was used to collect patient information by medical staff of each hemodialysis center (room) as investigators. Part of the demography data and laboratory examination data came from the Jiangsu Province Hemodialysis Data Information System. MHD patients from hemodialysis centers (rooms) at all levels of medical institutions and independent hemodialysis institutions in Jiangsu province during the outbreak of SARS-CoV-2 infection were included, and the clinical characteristics and all-cause mortality of confirmed and suspected cases of SARS-CoV-2 infection were analyzed.Results:Questionnaire surveys and data analysis on 57 278 patients in 407 hemodialysis centers (rooms) were completed, accounting for 90.41% of the total number of MHD patients (63 357 cases) in Jiangsu province during the same period. There were 24 038 cases (41.97%) of SARS-CoV-2 infection and 14 805 cases (25.85%) of suspected infection, which were widely distributed in all dialysis centers in Jiangsu province. After clinical classification of 38 843 confirmed and suspected SARS-CoV-2 infection cases, 3 662 cases were severe and critical cases, accounting for 9.43% of the infected and suspected cases. Among the patients who had completed the questionnaires, there were 1 812 all-cause deaths, with an all-cause mortality rate of 3.16%. Multivariate logistic regression analysis showed that elderly (taking ≤50 years as a reference, 51-59 years: OR=1.583, 95% CI 1.279-1.933, P=0.001; 60-69 years: OR=3.972, 95% CI 3.271-4.858, P<0.001; 70-79 years: OR=7.236, 95% CI 5.917-8.698, P<0.001; ≥80 years: OR=11.738, 95% CI 9.459-14.663, P<0.001), male ( OR=1.371, 95% CI 1.229-1.529, P<0.001), and co-infection with hepatitis B virus (HBV) (positive serum HBV surface antigen, OR=0.629, 95% CI 0.484-0.817, P<0.001) were independent influencing factors for all cause mortality. Receiver-operating characteristic curve analysis showed that the area under the curve for male, age and current HBV infection prediction of all-cause death was 0.529 ( P<0.001), 0.724 ( P<0.001) and 0.514 ( P=0.042), respectively, and the cut-off value for age prediction of all-cause death was 65.5 years old. Compared with patients without HBV infection, MHD patients with HBV infection significantly reduced the proportion of severe and critically ill patients, all-cause hospitalizations and all cause deaths when infected with SARS-CoV-2 (4.99% vs. 6.41%, χ2=6.136, P=0.013; 8.90% vs. 11.44%, χ2=11.662, P<0.001; 2.01% vs. 3.37%, χ2=10.713, P=0.001, respectively). Conclusion:The MHD patients in Jiangsu province are susceptible to SARS-CoV-2. Elderly age and male gender are independent risk factors for death in MHD patients during the epidemic, while the HBV infection may be a protective factor for death of MHD patients infected with SARS-CoV-2.

OBJECTIVE: To explore the long-term efficacy of allogeneic hematopoietic stem cell transplantation (alloHSCT) in patients with Mucopolysaccharidosis (MPS), which has rarely been reported in China. METHODS: A 18-month-old boy and a 23-month-old girl undergoing alloHSCT for MPS VI and MPS IH Shanghai Children's Medical Center on March 30, 2006 and September 6, 2006 were selected as the study subjects. A busulfan-based myeloablative regimen was used as the conditioning regimen. Peripheral stem cells were respectively collected from a human leucocyte antigen (HLA) matched sibling carrier donor and a HLA 9/10 matched unrelated donor. Both patients were followed up for more than 15 years. The functions of internal organs before and after the transplantation were compared, and child 1 was also compared with his untreated brother and healthy brother. RESULTS: Both children have achieved full donor chimerism after the transplantation, and their enzymatic activities have remained stable. The enzymatic activity of the child 1 was slightly lower than normal but similar to that of his carrier donor, whilst that of the child 2 was normal. Both children have attended schools with good academic performance. Compared with his untreated brother, the respiratory function and hearing of child 1 have significantly improved. However, his orthopedic and cardiac disorders have still remained and required medical intervention. For child 2, her obstructive pulmonary disease was resolved and cognitive development was well preserved after the HSCT. Her heart disease has become stabilized and even improved with time, though her corneal clouding and skeletal malformation still required surgery. CONCLUSION MPS patients can sustain long-term and stable enzymatic activities after successful alloHSCT. Compared with untreated patients, their health can be significantly improved, along with considerably prolonged survival, though the long-term efficacy of HSCT for different organs may vary to a certain extent.
Humans ; Child ; Male ; Female ; Infant ; Child, Preschool ; Graft vs Host Disease/etiology* ; China ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Mucopolysaccharidoses/etiology* ; Busulfan ; Treatment Outcome