OBJECTIVE To further standardize the dispensing management standard of intravenous infusion drugs for clinical trials in pharmacy intravenous admixture services （PIVAS）， and provide reference for medical institutions to provide high-quality pharmaceutical services. METHODS Initiated by PIVAS Group， Hospital Pharmacy Professional Committee， Shanghai Pharmaceutical Association， jointly led by Longhua Hospital， Shanghai University of Traditional Chinese Medicine and Shanghai Geriatric Medical Center， a writing group was established by PIVAS experts from multiple medical institutions to discuss the basic requirements and dispensing process of intravenous infusion drugs for clinical trials in PIVAS. The experts from the leading unit sorted out， summarized， analyzed， fed back and revised the opinions， and finally reached Expert Consensus on Dispensing Management of Intravenous Infusion Drugs for Clinical Trials in PIVAS. RESULTS & CONCLUSIONS The main contents of this consensus include information management， operation process， fund management and document management of intravenous infusion drugs for clinical trials in PIVAS. This consensus establishes a more standardized model for dispensing management of intravenous infusion drugs for clinical trials in PIVAS， by standardizing clinical trail drug management operational procedures， accurately recording and preserving drug-related information， with the aim of achieving standardized and meticulous management of PIVAS’s receipt of clinical trial drugs.

Objective:The predictive model of cardiac arrest in the emergency room was constructed and validated based on Logistic regression.Methods:This study was a retrospective cohort study. Patients admitted to the emergency room of the First Affiliated Hospital of Xinjiang Medical University from January 2020 to July 2021 were included. The general information, vital signs, clinical symptoms, and laboratory examination results of the patients were collected, and the outcome was cardiac arrest within 24 hours. The patients were randomly divided into modeling and validation group at a ratio of 7:3. LASSO regression and multivariable logistic regression were used to select predictive factors and construct a prediction model for cardiac arrest in the emergency room. The value of the prediction model was evaluated using the area under the receiver operator characteristic curve (AUC), calibration curve, and decision curve analysis (DCA).Results:A total of 784 emergency room patients were included in the study, 384 patients occurred cardiac arrest. The 10 variables were ultimately selected to construct a risk prediction model for cardiac arrest: Logit( P)= -4.503+2.159×modified early warning score (MEWS score)+2.095×chest pain+1.670×abdominal pain+ 2.021×hematemesis+2.015×cold extremities+5.521×endotracheal intubation+0.388×venous blood lactate-0.100×albumin+0.768×K ++0.001×D-dimer. The AUC of the model group was 0.984 (95% CI: 0.976-0.993) and that of the validation group was 0.972 (95% CI: 0.951-0.993). This prediction model demonstrates good calibration, discrimination, and clinical applicability. Conclusions:Based on the MEWS score, chest pain, abdominal pain, hematemesis, cold extremities, tracheal intubation, venous blood lactate, albumin, K +, and D-dimer, a predictive model for cardiac arrest in the in-hospital emergency room was constructed to predict the probability of cardiac arrest in emergency room patients and adjust the treatment strategy in time.

Epilepsy is a kind of brain dysfunction syndrome characterized by paroxysmal,transient,repetitive and rigid characteristics caused by abnormal discharge of highly synchronized neurons in the brain.Epilepsy is often accompanied by cognitive dysfunction.At present,anti-seizure medications are the most important methods of clinical treatment.Most of the traditional anti-seizure medications can cause cognitive dysfunction,and the influence of new anti-seizure medications on cognitive function is not completely clear.This paper reviews the influence of new anti-seizure medications on cognitive function and the possible related mechanisms of action based on relevant literature at home and abroad.It is expected that clinicians should pay attention to cognitive function in the process of diagnosis and treatment of epilepsy,and help clinicians realize the influence of anti-seizure medications on cognitive function,and rationally choose anti-seizure medications for patients.

Background::Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.Methods::This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied.Results::At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs. placebo, 95% CI 31%–69%) and 45% (low vs. placebo, 95% CI 26%–64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator’s Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310. Conclusion::CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.Trial Registration::ClinicalTrials.gov, NCT04805411.

Background::Bladder cancer, characterized by a high potential of tumor recurrence, has high lifelong monitoring and treatment costs. To date, tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types. Nonetheless, the existence of soft tumor cells in bladder tumors remains elusive. Thus, our study aimed to develop a microbarrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells.Methods::The stiffness of bladder cancer cells was determined by atomic force microscopy (AFM). The modified microfluidic chip was utilized to separate soft cells, and the 3D Matrigel culture system was to maintain the softness of tumor cells. Expression patterns of integrin β8 (ITGB8), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were determined by Western blotting. Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59 (TRIM59). The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models. Results::Using our newly designed microfluidic approach, we identified a small fraction of soft tumor cells in bladder cancer cells. More importantly, the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens, in which the number of soft tumor cells was associated with tumor relapse. Furthermore, we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells. Simultaneously, we detected a remarkable up-regulation in ITGB8, TRIM59, and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts.Conclusions::The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness. Meanwhile, the soft tumor cells become more sensitive to chemotherapy after stiffening, that offers new insights for hampering tumor progression and recurrence.

Objective:pH low insertion peptide (pHLIP)-variant 7 (var7)-fluorescein isothiocyanate (FITC) was used to explore an accurate imaging tool that targeted burn wounds to better perform burn debridement.Methods:Twelve rat models of burn wound were established and pHLIP-var7-FITC with different concentrations (0.5, 1.5 and 2.0 mg/ml) were injected from the rat tail vein for in vivo fluorescence imaging. By determining the concentration of fluorescent conjugates to the burn wound, the scope of wound injury necrosis was judged by combining pathological sections, and its residue and toxicity in important organs such as heart, liver, kidneys, and brain were detected. The Kruskal-Wallis rank sum test, Bonferroni correction method and one-way analysis of variance were used for data analysis. Results:Within 24 h, the fluorescence photons per unit area of the burn wound in the group of 0.5 mg/ml, 1.5 mg/ml and 2.0 mg/ml were 1.49(1.31, 1.65), 2.46(1.88, 2.68), 2.77 (1.94, 3.10)×10 7 p·s -1·cm -2·Sr -1, with significant differences in the overall distribution of fluorescence photons ( H=73.55, P<0.001). The fluorescence intensity was stronger in the group with higher concentration, but with no significant difference in the number of fluorescence photons between the group of 1.5 mg/ml and 2.0 mg/ml ( P=0.263, Bonferroni correction method). At 14 time points (0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 7.0, 8.0, 12, 24 h), there was no significant difference in the overall mean of fluorescence photons ( F=1.04, P=0.419), and the tissue with burn necrosis seen in tissue sections was highly consistent with the fluorescence imaging region. There was no obvious fluorescence residue in the heart, liver, kidney and brain sections. Conclusion:In superficial second-degree burn tissue, pHLIP-var7-FITC can accurately target and gather on the burn wound within 24 h, showing a clear boundary between burn tissue and normal tissue, which can assist clinical surgical debridement to determine the extent of injury.

Objective:To evaluate the effect of electroacupuncture on P2X4R-p38 mitogen-activated protein kinase (p38 MAPK)-brain-derived neurotrophic factor (BDNF) signaling pathway in trigeminal ganglion of rats with trigeminal neuralgia.Methods:Thirty-six clean-grade healthy adult male Sprague-Dawley rats, weighing 190-230 g, aged 2-3 months, were divided into 3 groups ( n=12 each) using a random number table method: sham operation group (S group), trigeminal neuralgia group (TN group), and electroacupuncture group (E group). The model was developed by chronic constriction of the infraorbital nerve in anesthetized animals. The infraorbital nerve was only exposed without ligation in group S. Rats received electroacupuncture stimulation at the Baihui and Xiaguan acupoints on the affected side for 20 min after developing the model, with a frequency of 80 Hz, twice a day, for 14 consecutive days in E group. Facial mechanical pain threshold (FMT) was measured at 1 day before developing the model and 3, 7, 14, 21 and 28 days after developing the model. The rats were sacrificed after the last behavioral testing, and the trigeminal ganglia were taken for examination of histopathological changes of trigeminal ganglion (by HE staining) and for determination of the expression of P2X4R, p38 MAPK, phosphorylated p38 MAPK (p-p38 MAPK) and BDNF (by Western blot) and contents of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and IL-6 (by enzyme-linked immunosorbent assay). Results:Compared with group S, the FMT was significantly decreased at each time point after developing the model, the expression of P2X4R, p-p38 MAPK and BDNF in trigeminal ganglion was up-regulated, and the contents of TNF-α, IL-1β and IL-6 were increased ( P<0.05), the pathological changes of the trigeminal ganglion were obvious in group TN. Compared with group TN, the FMT was significantly increased at each time point after developing the model, and the expression of P2X4R, p-p38 MAPK and BDNF in trigeminal ganglion was down-regulated, and the contents of TNF-α, IL-1β and IL-6 were decreased ( P<0.05), and the pathological changes of the trigeminal ganglion were significantly attenuated in group E. Conclusions:The mechanism by which electroacupuncture alleviates trigeminal neuralgia may be related to inhibiting the activity of P2X4R-p38MAPK-BDNF signaling pathway and reducing neuroinflammation in rats.

Objective:To compare hamstring tendon graft (HTG), ligament advanced reinforcement system (LARS), and mixed HTG & LARS ligament in reconstruction of posterior cruciate ligament (PCL).Methods:A retrospective study was conducted to analyze the 59 patients with PCL rupture who had been admitted to Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University for arthroscopic PCL reconstruction between January 2018 and August 2021. The patients were divided into 3 groups: in the HTG group of 21 cases [14 males and 7 females aged (37.8±12.6) years], PCL was reconstructed by HTG; in the LARS group of 20 cases [12 males and 8 females aged (34.3±9.1) years], PCL was reconstructed by LARS; in the mixed group of 18 cases [13 males and 5 females aged (33.2±8.3) years], PCL was reconstructed by the mixed HTG & LARS ligament. The 3 groups were compared in terms of Lysholm knee score, International Knee Documentation Committee (IKDC) score, and laxity disparity between bilateral knees at 1 and 2 years after surgery.Results:There was no statistically significant difference in the preoperative general data between the 3 groups, indicating comparability ( P>0.05). One year after surgery, the mixed group had a significantly higher IKDC score [(90.0±6.5) points] than the HTG group [(78.1±5.7) points] and the LARS group [(84.1±7.3) points], and a significantly higher Lysholm score [(88.9±5.5) points] and a significantly smaller laxity disparity between bilateral knees [(2.8±1.7) mm] than the HTG group [(81.8±4.6) points, (4.7±2.4) mm] ( P<0.05). Two years after surgery, the mixed group had a Lysholm score of (93.0±4.5) points, a IKDC score of (92.5±5.7) points, and a laxity disparity between bilateral knees of (2.3±1.8) mm, all significantly better than those in the HTG group [(88.5±5.5) points, (82.7±5.7) points, and (4.2±2.5) mm] and in the LARS group [(89.0±5.2) points, (86.5±7.3) points, and (3.8±2.2) mm] ( P<0.05). In all the 3 groups, the knee function scores and laxity disparities between bilateral knees at 1 and 2 years after surgery were significantly improved compared with the preoperative values ( P<0.05). Conclusions:Satisfactory clinical outcomes can be obtained after arthroscopic PCL reconstruction using HTG, LARS or the mixed HTG & LARS ligament. However, the mixed ligament as a graft can achieve better clinical efficacy than the other two grafts.

Objective:To evaluate the significance of the lumbar bowstring ratio (LBR) and sagittal spine-pelvis parameters in predicting postoperative neurogenic pain in adult patients with high-grade lumbar isthmic spondylolisthesis following spinal fusion surgery.Methods:A retrospective analysis was conducted on the clinical and imaging data of 95 adult patients with high-grade lumbar isthmic spondylolisthesis treated by spinal surgery at Xiangya Hospital of Central South University from August 2012 to January 2023. Each patient was followed for a minimum of six months. Participants were categorized into pain and non-pain groups based on the presence of persistent radicular pain (≥8 weeks) and a visual analogue scale (VAS) score of ≥3 postoperatively. The pain group comprised 15 patients (5 males, 10 females; mean age 55.47±6.42 years, range 46-71 years), while the non-pain group included 80 patients (20 males, 60 females; mean age 60.98±11.50 years, range 40-85 years). Clinical outcomes were assessed using the Oswestry Disability Index (ODI) and VAS scores. LBR was defined as the ratio of the vertical distance from the anterior convexity of the L 1-L 5 anterior longitudinal ligament to a line connecting the posterior superior margin of the L1 vertebra and the posterior margin of the S1 vertebra, to the distance between these two points. Spinal-pelvic parameters measured included pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), lumbar lordosis (LL), PT/SS ratio, and changes in LBR before and after surgery (ΔLBR). Statistical comparisons of demographic and imaging parameters were performed between the two groups, and variables showing significant differences were subjected to binary logistic regression analysis to identify independent risk factors for postoperative neurogenic pain. Results:All 95 patients achieved complete anatomical reduction of the dislocation without reported wound infections. Follow-up was completed at 7.68±2.98 months (range 6-12 months) postoperatively. Among the patients, 15 developed iatrogenic radicular pain. Postoperative complications included pulmonary infection (4 cases: 1 in the pain group, 3 in the non-pain group), cerebrospinal fluid leakage (8 cases: 2 in the pain group, 6 in the non-pain group), and delirium (5 cases: 2 in the pain group, 3 in the non-pain group). No significant differences were observed in demographic data between the groups ( P>0.05). Both groups demonstrated significant improvements in ODI (pain group Z=-3.413, P=0.001; non-pain group Z=-7.772, P<0.001) and VAS scores (pain group Z=-3.426, P=0.001; non-pain group Z=-7.838, P<0.001) at the 6-month follow-up compared to preoperative values. Significant differences were found between the pain and non-pain groups in PI ( t=3.315, P=0.004), PT ( t=5.087, P<0.001), SS ( t=7.431, P<0.001), LL ( t=3.764, P<0.001), PT/SS ( t=7.267, P<0.001), LBR ( t=6.455, P<0.001), and ΔLBR ( Z=5.362, P<0.001) before and after surgery. Binary logistic regression analysis identified smaller preoperative PT/SS [ OR=0.760, 95% CI(0.601, 0.961), P=0.022] and larger preoperative LBR [ OR=5.721, 95% CI (1.068, 30.634), P=0.042] as independent risk factors for postoperative neurogenic pain. Conclusion:High LBR and reduced PT/SS are significant risk factors for neurogenic pain following complete discectomy and fusion in adult patients with high-grade lumbar isthmic spondylolisthesis. For such patients, careful consideration is warranted regarding anatomical complete reduction during surgical intervention.

Objective This study aimed to reveal critical genes regulating peri-implantitis during its development and construct a diagnostic model by using random forest(RF)and artificial neural network(ANN).Methods GSE-33774,GSE106090,and GSE57631 datasets were obtained from the GEO database.The GSE33774 and GSE106090 da-tasets were analyzed for differential expression and functional enrichment.The protein-protein interaction networks(PPI)and RF screened vital genes.A diagnostic model for peri-implantitis was established using ANN and validated on the GSE33774 and GSE57631 datasets.A transcription factor-gene interaction network and a transcription factor-micro-RNA(miRNA)regulatory network were also established.Results A total of 124 differentially expressed genes(DEGs)involved in the regulation of peri-implantitis were screened.Enrichment analysis showed that DEGs were mainly associated with immune receptor activity and cytokine receptor activity and were mainly involved in processes such as leukocyte and neutrophil migration.The PPI and RF screened six essential genes,namely,CD38,CYBB,FCGR2A,SELL,TLR4,and CXCL8.The receiver oper-ating characteristic curve(ROC)indicated that the ANN model had an excellent diagnostic performance.FOXC1,GA-TA2,and NF-κB1 may be essential transcription factors in peri-implantitis,and hsa-miR-204 may be a key miRNA.Con-clusion The diagnostic model of peri-implantitis constructed by RF and ANN has high confidence,and CD38,CYBB,FCGR2A,SELL,TLR4,and CXCL8 are potential diagnostic markers.FOXC1,GATA2,and NF-κB1 may be essential transcription factors in peri-implantitis,and hsa-miR-204 plays a vital role as a critical miRNA.