OBJECTIVE To optimize the prescription pre-review system in our hospital and evaluate its application effects. METHODS Aiming at the problems of imperfect rule base and high false positive rate in the early operation of the system， optimization measures were taken， including improving the content of the rule base， adjusting the interception level and prompt mode， refining the working model of prescription review pharmacists， and strengthening clinical communication. A retrospective cohort study was conducted， with prescription data from June to December 2023 （before optimization） as the control group and June to December 2024 （after optimization） as the observation group. Through inter group comparative analysis， the actual effect of optimizing the prescription pre-approval system was evaluated. RESULTS The prescription qualified rate increased from （82.51± 4.04）% before optimization to （90.98±1.55）% after optimization； the false positive rate decreased from （20.87±1.64）% before optimization to （7.41±2.04）% after optimization. The monthly range of prescription qualified rate narrowed from 10.24% to 4.11%， and the coefficient of variation decreased from 4.92% to 1.73%. The monthly range of false positive rate slightly increased from 4.40% to 5.34%， the coefficient of variation rose from 8.32% to 26.18%. CONCLUSIONS Through multi-dimensional optimizations of the prescription pre-review system in our hospital， its prescription review efficiency has been significantly enhanced， the quality of prescriptions has steadily improved， and the accuracy of reviews has notably improved.

Objective To study the value of DSI Studio combined with diffusion tensor imaging(DTI)in evaluating the prognosis of postoperative motor function in patients with brain functional area tumors.Methods From January 2018 to August 2022,41 patients with brain functional area tumors who underwent surgical treatment and were pathologically diagnosed in our hospital were included in the study.All patients completed 3.0 T MRI routine sequence and DTI examination.DTI parameters of the corticospinal tract(CST)projection area of posterior limb of the internal capsule on the affected side and the healthy side were measured respectively,and the correlation with MRC muscle strength score and the CST grade was analyzed.Results The FA value of the affected side was significantly lower than that of the healthy side(P＜0.001),and the ADC value of the affected side was significantly higher than that of the healthy side(P＜0.001).The FA value of the affected side and the lateral rFA value were negatively correlated with the CST grade(P＜0.01).ADC value and rADC value were positively correlated with CST grade(P＜0.01).The FA value of the affected side and the partial rFA value were positively correlated with the degree of muscle strength score before and after surgery(P＜0.01).ADC value and rADC value were negatively corre-lated with CST grade(P＜0.01).Preoperative CST grading was negatively correlated with contralateral muscle strength.The area under the ROC curve of FA value,rFA value,ADC value,rADC value,and CST grade were 0.820(P＜0.01),0.796(P＜0.01),0.698(P＜0.05),0.638(P＞0.05)and 0.708(P＜0.05),respectively.Conclusion DTI parameters,muscle strength score and CST grade have certain value in the evaluation of postoperative motor function prognosis in patients with brain functional tumors.

Objective To investigate the role of Rho/ROCK signaling pathway in mediating restraint stress-induced blood-brain barrier(BBB)injury in the amygdala of rats.Methods Sixty male SD rats were randomized equally into control group(with food and water deprivation for 6 h per day),restraint stress group(with restraint for 6 h per day),stress + fasudil treatment(administered by intraperitoneal injection at 1 mg/100 g 30 min before the 6-h restraint)group,and fasudil treatment alone group.The elevated plus-maze test was used to detect behavioral changes of the rats,serum corticosterone and S100B levels were determined with ELISA,and Evans Blue leakage in the brain tissue was examined to evaluate the changes in BBB permeability.The changes in expression levels of tight junction proteins in the amygdala were detected using immunofluorescence assay and Western blotting,and Rho/ROCK pathway activation was detected by Pull-down test and Western blotting.Ultrastructural changes of the cerebral microvascular endothelial cells were observed using transmission electron microscopy.Results Compared with those in the control group,the rats in restrain stress group and stress+fasudil group showed obvious anxiety-like behavior with significantly increased serum corticosterone level(P<0.001).Compared with those in the control group and stress+fasudil group,the rat models of restrain stress showed more obvious Evans Blue leakage and higher S100B expression(P<0.01)but lower expressions of tight junction proteins in the amygdala.Pull-down test and Western blotting confirmed that the expression levels of RhoA-GTP,ROCK2 and P-MLC 2 were significantly higher in stress group than in the control group and stress + fasudil group(P<0.05).Transmission electron microscopy revealed obvious ultrastructural changes in the cerebral microvascular endothelial cells in the rat models of restrain stress.Conclusion Restraint stress induces BBB injury in the amygdala of rats by activating the Rho/ROCK signaling pathway.

Objective To investigate the role of Rho/ROCK signaling pathway in mediating restraint stress-induced blood-brain barrier(BBB)injury in the amygdala of rats.Methods Sixty male SD rats were randomized equally into control group(with food and water deprivation for 6 h per day),restraint stress group(with restraint for 6 h per day),stress + fasudil treatment(administered by intraperitoneal injection at 1 mg/100 g 30 min before the 6-h restraint)group,and fasudil treatment alone group.The elevated plus-maze test was used to detect behavioral changes of the rats,serum corticosterone and S100B levels were determined with ELISA,and Evans Blue leakage in the brain tissue was examined to evaluate the changes in BBB permeability.The changes in expression levels of tight junction proteins in the amygdala were detected using immunofluorescence assay and Western blotting,and Rho/ROCK pathway activation was detected by Pull-down test and Western blotting.Ultrastructural changes of the cerebral microvascular endothelial cells were observed using transmission electron microscopy.Results Compared with those in the control group,the rats in restrain stress group and stress+fasudil group showed obvious anxiety-like behavior with significantly increased serum corticosterone level(P<0.001).Compared with those in the control group and stress+fasudil group,the rat models of restrain stress showed more obvious Evans Blue leakage and higher S100B expression(P<0.01)but lower expressions of tight junction proteins in the amygdala.Pull-down test and Western blotting confirmed that the expression levels of RhoA-GTP,ROCK2 and P-MLC 2 were significantly higher in stress group than in the control group and stress + fasudil group(P<0.05).Transmission electron microscopy revealed obvious ultrastructural changes in the cerebral microvascular endothelial cells in the rat models of restrain stress.Conclusion Restraint stress induces BBB injury in the amygdala of rats by activating the Rho/ROCK signaling pathway.

Objective:We aimed to develop a novel visualized model based on nomogram to predict postoperative overall survival.Methods:This was a multicenter, retrospective, observational cohort study, including participants with histologically confirmed gastric and colorectal cancer who underwent radical surgery from 11 medical centers in China from August 1, 2015 to June 30, 2018. Baseline characteristics, histopathological data and nutritional status, as assessed using Nutrition Risk Screening 2002 (NRS 2002) score and the scored Patient-Generated Subjective Global Assessment, were collected. The least absolute shrinkage and selection operator regression and Cox regression were used to identify variables to be included in the predictive model. Internal and external validations were performed.Results:There were 681 and 127 patients in the training and validation cohorts, respectively. A total of 188 deaths were observed over a median follow-up period of 59 (range: 58 to 60) months. Two independent predictors of NRS 2002 and Tumor-Node-Metastasis (TNM) stage were identified and incorporated into the prediction nomogram model together with the factor of age. The model's concordance index for 1-, 3- and 5-year overall survival was 0.696, 0.724, and 0.738 in the training cohort and 0.801, 0.812, and 0.793 in the validation cohort, respectively.Conclusions:In this study, a new nomogram prediction model based on NRS 2002 score was developed and validated for predicting the overall postoperative survival of patients with gastric colorectal cancer. This model has good differentiation, calibration and clinical practicability in predicting the long-term survival rate of patients with gastrointestinal cancer after radical surgery.

To explore the effect of Mlk3 (mixed lineage kinase 3) deficiency on blood pressure, Mlk3 gene knockout (Mlk3KO) mice were generated. Activities of sgRNAs targeted Mlk3 gene were evaluated by T7 endonuclease I (T7E1) assay. CRISPR/Cas9 mRNA and sgRNA were obtained by in vitro transcription, microinjected into zygote, followed by transferring into a foster mother. Genotyping and DNA sequencing confirmed the deletion of Mlk3 gene. Real- time PCR (RT-PCR), Western blotting or immunofluorescence analysis showed that Mlk3KO mice had an undetectable expression of Mlk3 mRNA or Mlk3 protein. Mlk3KO mice exhibited an elevated systolic blood pressure compared with wild-type mice as measured by tail-cuff system. Immunohistochemistry and Western blotting analysis showed that the phosphorylation of MLC (myosin light chain) was significantly increased in aorta isolated from Mlk3KO mice. Together, Mlk3KO mice was successfully generated by CRISPR/Cas9 system. MLK3 functions in maintaining blood pressure homeostasis by regulating MLC phosphorylation. This study provides an animal model for exploring the mechanism by which Mlk3 protects against the development of hypertension and hypertensive cardiovascular remodeling.
Animals ; Mice ; Mice, Knockout ; CRISPR-Cas Systems ; Blood Pressure ; Gene Knockout Techniques ; Zygote

Objective:To investigate the effect and underlying mechanism of BRCC3 knockout on acute GVHD(aGVHD) of mice.Methods:A total of 12 recipient C57BL/6J mice were divided into two groups, including 6 wild type(WT) and BRCC3 -/-(KO). The recipients were exposed to 4.5 Gy + 4.5 Gy 60Co γ-rays in total body irradiation (TBI) at 30 min intervals. At 6 h post-irradiation, 1×10 7bone marrow cells and 8×10 6 splenocytes from BALB/c mice were infused into C57BL/6J mouse via tail vein to develop aGVHD mouse model. BRCC3 was specifically knocked out in aGVHD mouse model. The organ damage was examined through histopathology. The levels of serum cytokines were measured by enzyme-linked immuno sorbent assay (ELISA) and cytometric bead array (CBA), respectively. Spleen, liver and small intestine lymphocytes were isolated at 9 d post-transplantation, and the infiltration and activation of T cells in the target organs were assayed using flow cytometry. Results:The absence of BRCC3 in recipient mice significantly shortened survival ( P<0.05) with increased liver injury of aGVHD mice. In BRCC3 -/-recipient mice, the proportions of CD8+ T cells and CD8+ CD25+ T cells were significantly higher than those in the spleen( t=6.53, 5.52, P<0.05), and the proportions of CD8+ T cells and CD8+ CD25+ T cells were significantly increased in the liver ( t=3.74, 3.19, P<0.05). Similarly, the proportions of CD8+ T cells, CD8+ CD25+ T cells and CD8+ CD69+ T cells were significantly elevated in the small intestine ( t=3.52, 4.06, 3.29, P<0.05). Conclusions:BRCC3 deletion increased the proliferation and activation of donor CD8+ T cells and aggravated aGVHD, which might provide a new prevention and treatment target for aGVHD.

Objective:To investigate the changes in total radioactivity in patient body with differentiated thyroid carcinoma (DTC) after 131I treatment and the factors influencing its metabolism. Methods:The clinical data from 218 patients after DTC treatment in the Department of Nuclear Medicine, the Second Affiliated Hospital of Air Force Medical University from September 2021 to April 2022 were retrospectively analyzed. Based on administrated 131I dose, 171 patients were divided into low-dose group (≤ 3.7 GBq) and 47 into high-dose group (>3.7 GBq) . A whole body dynamic radiation monitoring system was used to measure the in vivo residual activity of 131I 24, 48 and 72 h after 131I administration and to explore their influencing factors. Results:24, 48 and 72 h after adimination of 131I, the residual activity of 131I in the low-dose group patients was significantly lower than in the high-dose group patients ( t= -7.46, -3.31, -2.01, P<0.05) . The discharge compliance rate at 24 and 48 h in the low-dose group was significantly higher than that in the high-dose group (21.0% vs. 4.3%, 98.2% vs. 89.4%, χ2 = 7.23, 5.91, P<0.05) , and all patients could meet the discharge criteria at 72 h. Univariate analysis showed that the residual 131I activity at 24 and 48 h was dependent on age, body mass index (BMI) , basal metabolism rate (BMR) and thyroid stimulating hormone (TSH) . As have been shown by multiple linear regression analysis, in the low-dose group, the older age, the higher BMR and the higher TSH level at 24 h tended to the higher 131I residual activity in the body. At 48 h, the higher BMI and the higher TSH level lead to the higher 131I residual activity in patient body. Meanwhile, in the high-dose group, the higher age and BMR at 24 h, tended to the higher in vivo131I residual activity. The influencing factors were analyzed in terms that 131I residual activity reaching 400 MBq in patient body at 24 and 36 h. The result showed that at 24 h the lower TSH level leaded to the lower 131I residual activity in patient body. At 36 h, the younger age, the lower TSH level, and the smaller 131I treatment dose tended to the lower in vivo131I residual activity. Conclusions:Age, BMI, BMR and TSH levels are the influencing factors for the change in total activity in patient body after 131I treatment of DTC. Radiation dose assessment based on the above indicators can provide a reference for adjusting the length of hospitalization time.

Objective:To compare the proportion of abnormal renal function indexes in outpatients with chronic hepatitis B (CHB), and to further explore the correlation between the history of nucleos(t)ide analogues (NA) antiviral therapy and abnormal renal function indexes.Methods:A cross-sectional design was adopted for renal function screening. Baseline characteristics, history of antiviral treatment, and renal function indexes were collected, including glomerular filtration rate (eGFR), blood urea nitrogen, blood creatinine, blood uric acid, and urine β2- microglobulin α 1-microglobulin and urinary protein. According to the definition and standard of abnormal renal function indexes, the correlation between chronic kidney disease (CKD) - 1/2 and related risk factors, renal tubular indicators and risk factors, and the correlation between antiviral treatment duration and renal tubular risk were analyzed. The data were analyzed by single and multi-factor regression.Results:2703 outpatients from 47 hospitals across the country were enrolled. 70.7% were males with an average age of 47.5 years. 15.5% of cases had hypertension, 14.6% cases had chronic kidney disease, 11.3% cases had diabetes, and 15.4% had CKD 1/2. Retinol-binding protein, urinary β2-microglobulin or urinary α1-microglobulin showed renal tubular damage rates of 10.4%, 27.1% and 18.4%, respectively. Renal tubular damage risk was related to the antiviral treatment duration ( OR = 1.06, 95% CI = 1.028 ~ 1.093). Multivariate analysis results showed that the risk factors related to eGFR < 90 ml/min in male were 40-60 or > 60 years old, high viral load, poorly controlled hypertension, use of nephrotoxic drugs, liver fibrosis status, family history of hepatitis B; while the risk factors related to eGFR < 60 ml/min in female were decompensated cirrhosis, poorly controlled diabetes, and family history of hepatitis B. Conclusion:CHB outpatients have a high proportion of chronic kidney damage, including early renal tubular damage, which suggests that baseline renal function should be assessed before NA use and closely monitored during the treatment. Regular monitoring of the renal tubular damage index can detect the risk of kidney damage earlier than the estimated eGFR.

Squamous cell carcinoma (SCC) of the renal pelvis is extremely rare and hardly to be diagnosed due to its lack of specificity in clinical manifestations and traditional imaging features. We reported a case with history of multiple operations for double kidney stones, who was admitted to our hospital twice due to "right kidney ureteral stones, left kidney complex stones, chronic renal insufficiency and urinary tract infection" . During this period, a total of 6 surgeries were performed. In the first 19-day hospitalization, right transurethral ureteroscopic lithotripsy and right percutaneous nephroscope lithotripsy(PCNL)were performed respectively. And 20 days later, the patient was admitted to hospital again for management of left complex kidney stones, and the left side PCNL was performed for 4 times within 27 days. During the two hospitalizations, no tumor was reported during the three times of contrast-enhanced CT examination of the urinary system. The patient continued to have fever after the 4th time of left PCNL, with failure of anti-infection treatment. Then, the of the left renal pelvis was considered clinically, and left nephrectomy was suggested after communication with the patient and his family members. Postoperative pathology confirmed renal pelvis SCC. After surgery, the patient’s temperature was back to normal and then discharged. The patient died 3 months after discharging due to the systemic metastasis.