OBJECTIVE To provide a basis for the rational use of nonsteroidal anti-inflammatory drugs （NSAIDs） in the perioperative period， and provide practical methods and technical references for the evaluation and selection of NSAIDs in medical institutions. METHODS Initiated by the Affiliated Hospital of Qingdao University， Clinical Pharmacy Professional Committee of the Shandong Pharmacists Association， Clinical Individualised Drug Testing and Guidance Branch of the Shandong Medical Association， Comprehensive Clinical Medication Evaluation Working Committee of the Shandong Pharmacists Association， Pain Branch of the Shandong Medical Association in conjunction with several medical institutions in Shandong Province organized 22 pharmaceutical experts and medical experts from 17 hospitals in Shandong Province to form a consensus on the rational use and comprehensive clinical evaluation of NSAIDs in the perioperative period through the literature research method， expert interview method and questionnaire survey method based on evidence-based medicine. A comprehensive clinical evaluation was also conducted on a total of 13 specifications of 9 commonly used clinical drug varieties in Shandong Province， including celecoxib， etoricoxib， imrecoxib， ibuprofen （containing reference/original drugs and national/Shandong Province’s centralized volume-based procurement varieties）. RESULTS & CONCLUSIONS A consensus opinion was formed on preoperative prophylactic use and postoperative use of NSAIDs， as well as contraindications， digestive tract risk， cardiovascular system risk， bleeding risk and kidney injury risk in the perioperative period. The evaluation and selection criteria of perioperative use of NSAIDs were established， involving 6 dimensions of safety， efficacy， economy， innovation， appropriateness， and accessibility. The results of comprehensive clinical evaluation showed that the top 6 drugs （scores over 70） were Celecoxib capsules （Celebrex） and Celecoxib capsules （Naiqi）， Diclofenac sodium sustained-release tablets，Etocoxib tablets （Arcoxia） and Etocoxib tablets （Qimingshu）， and Parecoxib sodium for injection. With the progress of clinical research， this consensus will be further updated and adjusted， and medical institutions can combine with the practice to develop a comprehensive clinical evaluation system of NSAIDs suitable for their institutions.

Objective: To explore the factors affecting the prognosis of children with status epilepticus(SE). Methods: A retrospective review was performed on children and the outcomes were measured by Glasgow Outcome Score (GOS). GOS=5 was defined as a good outcome, and GOS<5 as a bad outcome. Results: (1)Two hundred and ninety-eight children (163 girls and 135 boys) with SE were enrolled.The ages of the patients ranged from 2 months and 7 days to 14 years and 5 months, and 106 cases were at 1-3 years old.There were 154 cases (51.68%) with previous history of convulsion, including 98 cases of epilepsy (63.63%) and 241 new onset SE (80.87%). The most common cause of SE in children was febrile seizure (92 cases, accounting for 30.87%), followed by long-term symptom (81 cases, accounting for 27.18%). A total of 109 cases (41.90%) were treated with Diazepam in time after the convulsion, and 151 cases (58.10%) were treated with antiepileptic drugs such as Phenobarbital sodium or Chloral hydrate after the convulsion.Based on GOS scale, the near-term prognosis was as follows: 254 cases(85.23%) of children with GOS=5, and the remaining 44 cases of GOS<5 points.(2) Recent overall prognostic factors: single factor analysis showed that a total of 12 factors were associated with poor prognosis (P<0.05), including age, Pediatric Intensive Care Unit (PICU), tracheal intubation, previous history of convulsions, developmental delay, new onset of SE, fever, comprehensive onset, refractory SE, electroencephalogram (EEG) abnormality, neuroimaging abnormality and etiology.Multiple factor Logistic regression analysis showed that PICU monitoring was required (OR=4.306, 95%CI: 1.554-11.933, P=0.005), developmental delay (OR=3.054, 95%CI: 1.157-8.066, P=0.024), and abnormal cranial image (OR=2.110, 95%CI: 1.121-3.970, P=0.021) was an independent risk factors for short-term poor prognosis.Comprehensive onset (OR=0.330, 95%CI: 0.139-0.782; P=0.012), and the cause of febrile convulsion (OR=0.688, 95%CI: 0.480-0.987, P=0.042) were prognostic non-risk factor.(3)Recent prognostic factors in PICU monitoring group: the hospitalization time of PICU, developmental delay, the atypical attack type, electroencephalogram abnormality, neuroimaging abnormality, and the etiology of these 6 factors were correlated with the prognosis of PICU group, among which prolonged PICU (OR=36.912, 95%CI: 5.165-263.787, P=0.000) and developmental delay (OR=14.403, 95%CI: 1.725-120.273, P=0.014) were independent risk factors for poor outcome of PICU monitoring group. Conclusions PICU monitoring, developmental backwardness and abnormal head image are the independent risk factors for poor prognosis.PICU residence time and developmental delay are the independent risk factors for poor short-term prognosis in PICU enrolled children.

Objective: To investigate the clinical manifestations, imaging features, clinicopathologic features, and differential diagnosis of solitary fibrous tumors/anginoblastomas (SFT/HPCs) originating in the central nervous system. Methods: Sixty cases of SFT/HPCs originating in the central nervous system were collected at Nanjing Jinling Hospital, from January 1, 2008 to December 31, 2016. The clinical data, imaging data, histomorphologic changes and immunohistochemical finding were analyzed in the sixty cases. Results: The 60 cases included 26 males and 34 females, aged 14 to 85 (median 49) years. The main clinical manifestations were headache, dizziness with nausea and vomiting. Radiologically, the tumors were large, enhancing, solid and cystic masses attached to the dura. Histopathologically, the neoplasms were composed of spindle cells with oval nuclei, inconspicuous nucleoli and moderate amount of eosinophilic cytoplasm arranged in fascicles with areas of hyalinized stroma, myxoid changes and a staghorn vascular pattern. Immunohistochemically, tumor cells of all cases were positive for vimentin (100.0%, 60/60), STAT6 (98.3%, 59/60), CD34 (61.7%, 37/60), and the tumor cells were typically positive for CD99, bcl-2, EMA and SSTR2 as well.Negative for S-100 protein, SOX10, E-cadherin, GFAP. Ki-67 index ranged from 1% to 50%. Forty cases were followed up for 6 to 82 months with average of 40 months, 30 patients were alive and 10 patients died. Conclusions Central nervous system SFT/HPCs can be aggressive and relapses may occur several years after diagnosis. STAT6 is highly sensitive and specific for the diagnosis. Complete tumor resection is optional treatment followed by radiotherapy and chemotherapy. There is a correlation between the prognosis and the location of the disease, the histological grade, Ki-67 index, and fusion gene variants.

Objective: To observe the effects of different concentrations and doses of urea on the proliferation and apoptosis of human hemangioma endothelial cells, in order to provide evidence for the further mechanism study of urea in the treatment of hemangioma. Methods: Human hemangioma endothelial cells (HemECs) and normal endothelial cells (VE) were cultured in vitro. Cell viability was detected by CCK-8 after invention with different concentrations(40%, 50%, 60%, 70%) and doses(3, 6, 9 μl/ml) of urea. The apoptosis of HemECs was detected by flow cytometry dual-dye and propidium lodide single dye. Results: The viability of HemECs was significantly lower than that of VE under different concentrations and doses of urea (P<0.05). The inhibition rate of 40% urea on HemECs increased with the increase of urea dose (P<0.05), and the inhibition effect was most obvious at 4 h and 12 h. The apoptosis of HemECs increased in a time and dosage dependent manner with the treatment of 40% urea. High dose(9 μl/ml)of 40% urea significantly promoted the apoptosis of HemECs(P<0.05). Conclusions Low dose of 40% urea significantly inhibited the proliferation of HemECs, and had no significant effect on VE. However, high doses of urea promoted apoptosis of HemECs.

Objective: To investigate the association between the home blood pressure (BP) and morality in peritoneal dialysis (PD). Methods: PD patients from the First Affiliated Hospital of Zhejiang University from January 1, 2008 to June 30, 2016 were studied. Over the first 6 months PD therapy, systolic SB (SBP) and diastolic BP (DBP) averaged as 5 (<120 to≥150 mmHg in 10 mmHg increments) and 4 (<70 to≥90 mmHg in 10 mmHg increments) categories, respectively, as well as continuous measures. All-cause and cardiovascular mortality were assessed by using Cox regression models adjusted for demographics, laboratory measurements, comorbid conditions and antihypertensive medications. The relationships between home BP and all-cause and cardiovascular mortality were assessed by restricted cubic spline regression model. Results: A total of 1663 PD patients were included with a median follow-up of 29.9 months, in which 737 patients (44.3%) were female. The SBP and DBP were (135.2±15.8) mmHg and (83.1±10.5) mmHg, respectively. Two hundred and twenty-one PD patients died during the study period, of which 102 patients (46.2%) died of cardiac-cerebral vascular events. With 130≤SBP<140 mmHg as a refernece, SBP≥150 mmHg (HR=1.83, 95%CI 1.19-2.82, P=0.005) and SBP<120 mmHg (HR=2.05, 95%CI 1.29-3.27, P<0.001) were associated with significantly higher risks of all-cause morality, but not cardiovascular morality. With 80≤DBP<90 mmHg as a refernece, patients with DBP≥90 mmHg exhibited significantly higher risks of all-cause mortality (HR=1.80, 95%CI 1.21-2.68, P=0.009). SBP presented a U-shaped association with all-cause mortality. DBP presented a J-shaped association with all-cause mortality. Conclusions Higher SBP, lower SBP and higher DBP are associated with higher risks of all-cause mortality in PD patients. However, neither SBP nor DBP is observed statistically significant relationship with the risk of cardiovascular mortality. Further prospective and randomized clinical trials are needed to determine the optimal BP targets and improve the management of hypertension in PD patients.

Objective: To investigate the effect of a modified puncture cannula on prevention of bone cement leakage in percutaneous vertebroplasty (PVP). Methods: From January 2014 to February 2018, 243 patients with single-segmental osteoporotic vertebral fracture were treated with PVP at Department of Orthopedics, Shanghai Ninth People's Hospital. Their clinical data were retrospectively analyzed. Of them, a common puncture cannula was used in 169 cases (control group) and a modified puncture cannula in 74 (modified group). In the control group, there were 41 men and 128 women with an age of 71.6±9.5 years, and the fracture was distributed from T5 to T10 in 7 cases, from T11 to L2 in 132 and from L3 to L5 in 30. In the modified group, there were 20 men and 54 women with an age of 73.6±9.3 years, and the fracture was distributed from T5 to T10 in 3 cases, from T11 to L2 in 63 and from L3 to L5 in 8. The 2 groups were compared in terms of postoperative recovery of vertebral height, reduction in visual analogue scale(VAS) and bone cement leakage. Results: There were no significant differences between the 2 groups in age, gender, distribution of fractured vertebral bodies, compression degree, condition of vertebral posterior wall, or bone cement volume injected (P>0.05). There were no significant differences either between the control and modified groups in the postoperative recovery of vertebral height (7.43%±7.82% versus 6.20%±7.84%) or reduction in VAS score (5.83±0.99 versus 5.81±0.89) (P>0.05). Bone cement leakage occurred in 93 cases (55.0%) in the control group but in 26 cases (35.1%) in the modified group, showing a significant difference (P<0.05). The incidences of bone cement leakage in the paravertebral vessels [13.5% (10/74)], paravertebral soft tissue [9.5%(7/74)] and spinal canal [4.1%(3/74)] in the modified group were all significantly lower than those in the control group [25.4%(43/169), 20.1%(34/169) and 15.4%(26/169)](P<0.05). Conclusion Application of the modified end-to-side puncture cannula is an optional scheme to prevent bone cement leakage in PVP, because it can reduce the incidence of bone cement leakage without compromising postoperative short-term outcomes, especially in the spinal canal, paraspinal vessels and paraspinal soft tissue.

Objective: To analyze the distribution of glomerular immunofluorescence IgG4 subtypes in primary membranous nephropathy, and to explore the relationship between IgG4 deposit intensity and renal pathology, clinical manifestations and prognosis. Methods: All the patients of biopsy-proven primary membranous nephropathy with IgG staining and at least one IgG subtype staining 1+ or higher on capillary loops from September 2015 to April 2017 were retrospectively enrolled. The distribution of IgG4 deposits were analyzed, and the relationship between IgG4 positive intensity and clinical manifestations, pathological indexes and clinical remission was investigated. Results: A total of 250 cases were enrolled, including 157 males (62.8%) and 93 females (37.2%), and age was (54.4 ± 14.6) years. There were 40 patients in IgG4-negative group, and 210 patients in IgG4-positive group. The IgG4-positive group was divided into subgroups as 114 cases of the mild positive subgroup (1+) and 62 cases of the moderate positive subgroup (2+), and 34 cases of the strong positive subgroup (3+, 4+). The IgG4-positive group had higher 24-hour urine protein and higher positive rate of phospholipase A2 receptor staining than those in the negative group (both P<0.05), while the strong positive subgroup had lower serum albumin and higher IgG1 staining than those in the mild positive subgroup (both P<0.05). There was no difference in the ratio of glomerular sclerosis, tubular atrophy, IgG2, IgG3 or other immunofluorescence between the groups. After a median follow-up of 180(122, 209) days, 32 individuals were lost to follow-up. Among the rest 218 patients, 45 patients (20.6%) got complete remission, 104 patients (47.7%) got partial remission, and 69 patients (31.7%) showed no response. For no response as the outcome event, multivariate Cox regression analysis showed that higher IgG4 staining intensity (HR=1.371, 95%CI 1.068-1.759, P=0.013), male (HR=1.818, 95%CI 1.028-3.214, P=0.040), higher 24-hour urine protein level (HR=1.108, 95%CI 1.003-1.225, P=0.043) were independent risk factors for disease remission. Conclusions The glomerular IgG4 positivity and intensity are related to the severity of primary membranous nephropathy. The glomerular IgG4 deposit degree may be an effective prognostic marker for the treatment response of primary membranous nephropathy.

With the development of the Scientific, Transparent and Applicable Rankings tool for clinical practice guidelines(STAR), the publication of evaluation and ranking for scientificity, transparency and applicability of Chinese guidelines and consensus published in the medical journals in 2021and 2022, as well as the publication of the STAR evaluation and ranking for some specialities, the STAR evaluation and ranking has received widespread attention in the medical community. In order to further enhance its scientificity and transparency, Methodology and Technology Specialization Committee of the STAR Working Group presents this article to introduce sample identification and speciality assignment in the evaluation and ranking process.

Objective: To evaluate the relationship between p38 mitogen-activated protein kinase (p38MAPK) and G protein-coupled receptor kinase 2 (GRK2) in the development of persistent postoperative pain in rats. Methods: Pathogen-free healthy male Sprague-Dawley rats, weighing 200-250 g, aged 2 months, were used in this study.Sixty rats in which intrathecal catheters were successfully implanted were divided into 6 groups (n=10 each) using a random number table method: sham operation group (group S), sham operation plus dimethyl sulfoxide (DMSO) group (group D), sham operation plus GRK2 degradation inhibitor MDL28170 group (group M), persistent postoperative pain group (group PPP), persistent postoperative pain plus DMSO group (group PPP+ D) and persistent postoperative pain plus MDL28170 group (group PPP+ M). Persistent postoperative pain was evoked by skin/muscle incision and retraction (SMIR). Immediately after operation and at 1, 2 and 3 days after operation, normal saline 20 μl was intrathecally injected once a day in S and PPP groups, 5% DMSO 10 μl was intrathecally injected once a day in D and PPP+ D groups, and MDL28170 10 μl (50 μg) was intrathecally injected once a day in M and PPP+ M groups.The mechanical paw withdrawal threshold (MWT) was measured at 1 day before operation and 3, 7, 14 and 21 days after operation (T_1-4). Four rats in each group were selected after behavioral testing at T₃ and sacrificed, and the L_4-6 segments of the spinal cord were removed for determination of the expression of phosphorylated p38MAPK (p-p38MAPK) by Western blot. Results: There was no significant difference in MWT at each time point or expression of p-p38MAPK among group S, group D and group M (P>0.05). Compared with group S, the MWT was significantly decreased, and the expression of p-p38MAPK was up-regulated in PPP, PPP+ D and PPP+ M groups (P<0.05). Compared with group PPP, the MWT was significantly increased, and the expression of p-p38MAPK was down-regulated in group PPP+ M (P<0.05), and no significant change was found in the MWT or expression of p-p38MAPK in group PPP+ D (P>0.05). Conclusion Down-regulated expression of spinal GRK2 can promote the activation of p38MAPK in the spinal cord and is involved in the development of persistent postoperative pain in rats.

Objective: To evaluate the efficacy and safety of steroids-free immunosuppressive therapy including tacrolimus, cyclosporin A, tripterygium glycosides or intravenous cyclophosphamide in membranous nephropathy (MN) patients combined with type 2 diabetes mellitus (T2DM). Methods: This study was a retrospective analysis of patients with T2DM complicated with biopsy proved MN in the First Affiliated Hospital, College of Medicine, Zhejiang University from January 2009 to January 2017. The patients were divided into steroids-free group and control group. The patients in steroids-free group were treated with one or two immunosuppressive agents except glucocorticoids. The patients in control group were treated with glucocorticoid combining with immunosuppressive agents. Results: A total of 64 patients were enrolled in this study. There were 26 cases in steroids-free group and 38 cases in control group. The total remission rate was 69.24% in steroids-free group and 73.68% in control group at 12 months. In a median follow up of 33(12-106) months, two patients in control group entered hemodialysis and one of them died after 1 year of dialysis. One patient in steroids-free group died of accidental death and no patient entered dialysis. All patients in control group had elevated blood glucose level, whereas only 5 patients in steroids-free group had elevated blood glucose and all these 5 patients used tacrolimus. Conclusion Immunosuppressive regimen without glucocorticoid treatment can reduce side effects on blood glucose level in MN patients with type 2 diabetes, with a certain rate of treatment response.