Objective To analyze the effect of different anesthesia induction time on postoperative circadian rhythm in patients undergoing robot-assisted radical prostatectomy.Methods A total of 103 pa-tients,aged 50-85 years,BMI 18-30 kg/m2,ASA physical status Ⅰ-Ⅲ,undergoing robot-assisted radi-cal prostatectomy from January 2022 to October 2022 were recruited.The patients were grouped according to the induction time:the morning 8:00-11:59 group(group M,n=53)and the afternoon 12:00-18:00 group(group A,n=50).D'Amico risk grade,duration of anesthesia,number of effective com-pressions of analgesic pump(D1)and actual compressions(D2)were recorded,D1/D2 were calculated.HR,MAP,SpO2 were recorded at 5 minutes after entrying the operation room(T0),5 minutes after anes-thesia induction(T,),5 minutes after the surgery start(T2),60 minutes after the surgery start(T3),at the end of surgery(T4)and 5 minutes after extubation(T5).BIS at T1-T4 were recorded.Sleeping status was assessed by the Athens insomnia scale(AIS)1 day before surgery,1 day and 3 days after surgery,and pain level was assessed 1 and 3 days after surgery using the digital rating scale(NRS).According to the re-sults of the morningness-eveningness questionnaire of sleep-wake assessment(MEQ-SA)1 day before surgery and 3 days after surgery,the patients'circadian rhythm was determined.Results There were no statistically significant differences in D'Amico risk grade,duration of anesthesia,D1/D2,HR,MAP,SpO2 and BIS at different time point,AIS scores 1 day before surgery,1 day and 3 days after surgery,and NRS scores 1 day and 3 days after surgery between the two groups.In group M,there were 11 cases(21％)of circadian rhythm changes,of which 5 people's circadian rhythm changed to"later"and 6 people's circadian rhythm changed to"earlier".In group A,there were 3 cases(6％)of circadian rhythm changes,of which 1 person's circadian rhythm changed to"later"and 2 people's circadian rhythm changed to"earlier".The rate of circadian rhythm change in group M was significantly higher than that in group A(P＜0.05).Conclusion The incidence of perioperative circadian rhythm alteration is significantly higher in patients undergoing robot-assisted radical prostatectomy who starts anesthesia in the morning than those in the after-noon.

Objective:To investigate the risk factors associated with mortality in patients with severe traumatic liver injury (TLI) and to establish and validate an early prediction model for mortality.Methods:A retrospective cohort study was conducted to analyze the clinical data of 273 patients with severe TLI admitted to the ICU from the medical information mart for the intensive care-IV (MIMIC-IV) database. The cohort consisted of 176 males and 97 females, with age ranging from 18 to 83 years [35.6 years(25.7,57.5)years]. The patients were divided into two groups based on in-hospital mortality: the survival group (253 patients, 92.7%) and the death group (20 patients, 7.3%). The two groups were compared with regards to gender, age, cause and type of injury, treatment method, massive blood transfusion, comorbidities as well as vital signs and laboratory tests measured within 24 hours of ICU admission. Univariate analysis was used to screen for risk factors associated with mortality in severe TLI patients. Independent risk factors for mortality were determined using multivariate Logistic regression analysis. Lasso regression was used to screen for predictors of mortality, and a nomogram prognostic model was then established through a multivariate Logistic regression analysis. The area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the discrimination of the model, while the Hosmer-Lemeshow goodness-of-fit test and calibration curve were used to evaluate the calibration of the model. The model′s clinical applicability was evaluated through decision curve analysis (DCA). Internal validation was performed by the 200 Bootstrap samples, and external validation was performed by using 163 patients with severe TLI from the emergency ICU collaborative research database (eICU-CRD). Finally, the predictive efficacy of the nomogram model was compared to other trauma or severity scores.Results:Univariate analysis showed that the age, cause of injury, massive blood transfusion, chronic liver disease and laboratory tests measured within 24 hours of ICU admission, including temperature, systolic blood pressure, diastolic blood pressure, mean arterial pressure, shock index, platelets, red blood cell distribution width (RDW), mean red blood cell hemoglobin concentration (MCHC), blood glucose, blood urea nitrogen, creatinine, anion gap, bicarbonate, prothrombin time (PT), activated partial thromboplastin time (APTT) and international normalized ratio (INR) were associated with the mortality of severe TLI patients ( P<0.05 or 0.01). Multivariate Logistic regression analysis revealed that age ( OR=1.08, 95% CI 1.03, 1.12, P<0.01), body temperature <36 ℃ ( OR=8.00, 95% CI 2.17, 29.53, P<0.01), shock index ( OR=9.59, 95% CI 1.76, 52.18, P<0.01) and anion gap ( OR=1.32, 95% CI 1.15, 1.53, P<0.01) were significantly associated with mortality in severe TLI patients. Lasso regression analysis selected 7 predictors, including age, body temperature<36 ℃, shock index, anion gap, chronic liver disease, creatinine and APTT. Based on these 7 predictors, a nomogram prediction model was developed. The AUC of the nomogram for predicting mortality was 0.96 (95% CI 0.94, 0.99), and the Hosmer-Lemeshow goodness-of-fit test indicated a good fit ( P>0.05). The calibration curve demonstrated excellent consistency between the predicted and actual probabilities, and DCA demonstrated that the model had good clinical net benefit at all risk threshold probability ranges. Internal validation confirmed the stability of the model ( AUC=0.96, 95% CI 0.92, 0.98), and external validation demonstrated good generalization ability ( AUC=0.95, 95% CI 0.91, 0.98). Moreover, the nomogram exhibited superior predictive efficacy compared with injury severity score (ISS), revised trauma score (RTS), trauma injury severity score (TRISS), sequential organ failure score (SOFA), acute physiological score III (APS III), Logistic organ dysfunction score (LODS), Oxford acute severity of illness score (OASIS) and simplified acute physiological score II (SAPS II). Conclusions:Age, body temperature <36 ℃, shock index and anion gap are independent risk factors for mortality in severe TLI patients. A nomogram prognosis model based on 7 predictors, namely age, body temperature <36 ℃, shock index, anion gap, chronic liver disease, creatinine and APTT exhibits good predictive efficacy and robustness, and is contributive to accurately assess the risk of mortality in severe TLI patients at an early stage.

Objective:To identify dose-volume parameters to predict the incidence of acute intestinal toxicity in cervical cancer patients after postoperative adjuvant radiotherapy.Methods:Clinical data of 93 cervical cancer patients who underwent postoperative adjuvant intensity-modulated radiotherapy (IMRT) were retrospectively evaluated. The dose-volume parameters comprised the absolute volume of the bowel receiving 5-45 Gy (5 Gy interval) radiation dose and the total volume of the bowel. The acute radiation-induced intestinal toxicity was evaluated by Radiation Therapy Oncology Group (RTOG) criteria. The association between the irradiated bowel volume and acute intestinal toxicity was analyzed.Results:A total of 26 (28%) patients experienced grade ≥2 acute intestinal toxicity. A strong relationship between grade ≥2 acute intestinal toxicity and the irradiated small bowel volume was observed at the total volume of small bowel, small bowel V 5 Gy, V 10 Gy and V 15 Gy (all P<0.05). Small bowel V 10 Gy ( HR=1.028, 95% CI, 0.993-1.062, P=0.029) and small bowel ?V 15 Gy( HR=0.991, 95% CI, 0.969-1.013, P=0.034)were the independent risk factors for evident acute intestinal toxicity. Conclusion:Dose-volume parameters of the small bowel can be used as predictors for the occurrence of grade ≥2 acute intestinal toxicity in cervical cancer patients undergoing postoperative adjuvant radiotherapy.

Objective:To investigate the expression of miRNA-221-3p (miR-221-3p) in pancreatic cancer cells and its effect on apoptosis of pancreatic cancer cells, and the possible related mechanisms.Methods:Pancreatic cancer cell line PATU8988T was selected and transfected with miR-221-3p mimics, miR-221-3p inhibitors and their corresponding negative control sequences using Lipofectamine 3000. PATU8988T cells were divided into negative control group (without any treatment), miR-221-3p mimics negative control group, miR-221-3p mimics group, miR-221-3p inhibitors negative control group, and miR-221-3p inhibitors group. Real-time quantitative fluorescence polymerase chain reaction (qRT-PCR) was used to detect the relative expression level of miR-221-3p, flow cytometry was used to detect the influence of miR-221-3p on apoptosis of pancreatic cancer cells, and Western blotting was used to detect the expressions of P53 and PTEN proteins in PATU8988T cell line.Results:The relative expression levels of miR-221-3p in negative control group, miR-221-3p mimics negative control group, miR-221-3p mimics group, miR-221-3p inhibitors negative control group and miR-221-3p inhibitors group were 1.02±0.18, 1.50±0.33, 2.96±0.70, 1.62±0.30, and 0.36±0.05, respectively, and the difference was statistically significant ( F = 12.61, P < 0.05); the relative expression level of miR-221-3p in miR-221-3p mimics group was higher than that in negative control group and miR-221-3p mimics negative control group ( t = 1.94, P < 0.05; t = 1.45, P < 0.05); the relative expression level of miR-221-3p in miR-221-3p inhibitors group was lower than that in negative control group and miR-221-3p inhibitors negative control group ( t = -0.65, P < 0.05; t = -1.26, P < 0.05). The apoptosis rates in negative control group, miR-221-3p mimics negative control group, miR-221-3p mimics group, miR-221-3p inhibitors negative control group and miR-221-3p inhibitors group were (8.60±0.20)%, (8.60±0.26)%, (4.27±0.31)%, (8.83±0.29)%, and (13.63±0.60)%, respectively, and the difference was statistically significant ( F = 253.80, P < 0.01); the apoptosis rates in miR-221-3p mimics group was lower than that in negative control group and miR-221-3p mimics negative control group ( t = -4.33, P < 0.05; t = 4.33, P < 0.05); the apoptosis rate in miR-221-3p inhibitors group was higher than that in negative control group and miR-221-3p inhibitors negative control group ( t = 5.03, P < 0.05; t = 4.80, P < 0.05). There was no statistical difference in expression levels of P53 and PTEN proteins between miR-221-3p mimics negative control group and miR-221-3p inhibitors negative control group (P53: t = 0.22, P > 0.05; PTEN: t = 0.33, P > 0.05); the expression levels of P53 and PTEN proteins in miR-221-3p mimics group were decreased compared with the miR-221-3p mimics negative control group (P53: t = 4.31, P < 0.05; PTEN: t = 8.49, P < 0.05); the expression levels of P53 and PTEN proteins in miR-221-3p inhibitors group were increased compared with the miR-221-3p inhibitors negative control group (P53: t = 5.17, P < 0.05; PTEN: t = 6.21, P < 0.05). Conclusions:miR-221-3p is highly expressed in pancreatic cancer PATU8988T cells, which can inhibit the apoptosis of pancreatic cancer cells. miR-221-3p may regulate the progression of pancreatic cancer through P53 and PTEN.

Model informed precision dosing for warfarin is to provide individualized dosing by integrating information related to patient characteristics, disease status and pharmacokinetics /pharmacodynamics of warfarin, through mathematical modeling and simulation techniques based on the quantitative pharmacology. Compared with empirical dosing, it can improve the safety, effectiveness, economy, and adherence of pharmacotherapy of warfarin. This consensus report describes the commonly used modeling and simulation techniques for warfarin, their application in developing and adjusting dosing regimens, medication adherence and economy. Moreover, this consensus also elaborates the detailed procedures for the implementation in the warfarin pharmacy service pathway to facilitate the development and application of model informed precision dosing for warfarin.

Objective:To summarize and analyze the clinical data of Chinese patients with colony-stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy, and clarify the phenotypic and genetic characteristics of Chinese patients.Methods:Medical history of patients with CSF1R-related leukoencephalopathy diagnosed from April 1, 2018 to January 31, 2021 in the department of neurology of 22 hospitals in China was collected, and scores of Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment Scale (MoCA), magnetic resonance severity scale were evaluated. Group comparison was performed between male and female patients.Results:A total of 62 patients were included, and the male-female ratio was 1∶1.95. The age of onset was (40.35±8.42) years. Cognitive impairment (82.3%, 51/62) and motor symptoms (77.4%,48/62) were the most common symptoms. The MMSE and MoCA scores were 18.79±7.16 and 13.96±7.23, respectively, and the scores of two scales in male patients (22.06±5.31 and 18.08±5.60) were significantly higher than those in females (15.53±7.41 , t=2.954, P=0.006; 10.15±6.26, t=3.328 , P=0.003). The most common radiographic feature was bilateral asymmetric white matter changes (100.0%), and the magnetic resonance imaging severity scale score was 27.42±11.40, while the white matter lesion score of females (22.94±8.39) was significantly higher than that of males (17.62±8.74 , t=-2.221, P<0.05). A total of 36 CSF1R gene mutations were found in this study, among which c.2381T>C/p.I794T was the hotspot mutation that carried by 17.9% (10/56) of the probands. Conclusions:The core phenotypic characteristics of CSF1R-related leukoencephalopathy in China are progressive motor and cognitive impairment, with bilateral asymmetrical white matter changes. In addition, there exist gender differences clinically, with severer cognitive impairment and imaging changes in female patients. Thirty-six CSF1R gene mutations were found in this study, and c.2381T>C/p. I794T was the hotspot mutation.

Objective:To evaluate the role of spinal ninjurin 2 (NINJ2) in the neuropathic pain (NP) and the relationship with nuclear factor kappa B (NF-κB) signaling pathway in rats.Methods:Thirty-two clean-grade healthy male Sprague-Dawley rats, weighing 230-260 g, aged 7-8 weeks, were divided into 4 groups ( n=8 each) using a random number table method: sham operation group (Sham group), NP group, NP plus NINJ2 interfering virus group (NP+ siRNA group) and NP plus control virus group (NP+ scrRNA group). After intrathecal catheterization, rats in sham group and NP group received normal saline 10 μl, while NP+ NINJ2 siRNA group and NP+ scrRNA group received NINJ2 siRNA 10 μl and scrRNA 10 μl, respectively.NP model was developed via ligation of tibial nerve and common peroneal nerve one week later.Sham group only exposed the sciatic nerve and its branches.The mechanical paw withdrawal threshold (MWT) on the operated side was measured on preoperative days 3 and 1 and postoperative days 1, 3, 5, 7, 10 and 14.The rats were sacrificed at postoperative day 14, and the lumbar enlargement segments of the spinal cord were harvested for determination of the expression of NINJ2 and phosphorylated NF-κB p65 (p-NF-κB p65) (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 Sham group, the MWT on the operated side was significantly decreased, the expression of NINJ2 and p-NF-κB p65 in spinal cord was up-regulated, and contents of TNF-α, IL-1β and IL-6 were increased on the postoperative days 3, 5, 7, 10 and 14 in the other three groups ( P<0.05). Compared with NP group, the MWT on the operated side was significantly increased, the expression of NINJ2 and p-NF-κB p65 in spinal cord was down-regulated, and contents of TNF-α, IL-1β and IL-6 were decreased on the postoperative days 3, 5, 7, 10 and 14 in NP+ siRNA group ( P<0.05), and no significant change was found in each parameter mentioned above at different time points in NP+ scrRNA group ( P>0.05). Conclusion:NINJ2 is involved in NP, which is related to activation of NF-κB signaling pathway in rats.

Objective:To evaluate the diagnostic value of platelet count(PC),PC to mean platelet volume(MPV) ratio(PC/MPV) and plateletcrit(PCT) in chronic periprosthetic joint infection(PJI).Methods:The medical records of 159 patients who underwent hip or knee revisions at Department of Joint Surgery, Affiliated Hospital of Qingdao University from August 2013 to June 2019 were retrospectively reviewed. There were 51 patients(26 knees and 25 hips) in the PJI group,which included 28 males and 23 females,aged (68.0±11.8)years (range:32 to 84 years)with a body mass index(BMI)of (26.1±3.6) kg/m2.There were 116 patients(19 knees and 97 hips) in the aseptic loosening(AL) group,including 67 males and 49 females,aged (70.3±8.9)years(range:49 to 89 years)with a BMI of (25.0±3.6)kg/m2.The plasma C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),PC,MPV,PC/MPV and PCT levels of the two groups were recorded and analyzed. Receiver operating characteristic curve was used to calculate the sensitivity and specificity of each biomarker,expect for MPV,and the diagnostic value of each biomarker was compared according to the area under the curve(AUC).Independent-sample t test or Mann-Whitney U test were used for comparison between groups. Results:Compared with AL group,AJI group had significantly higher levels of CRP,ESR,PC,PC/MPV and PCT(all P<0.05),but lower level of MPV ( P<0.05).The AUCs for CRP,ESR,PC,PC/MPV and PCT were 0.820, 0.829, 0.689, 0.668 and 0.676,respectively. Based on the Youden index,the optimal predictive cutoff for CRP was 11.12 mg/L,with a sensitivity of 74.4% and a specificity of 87.1%.The optimal predictive cutoff for ESR was 17.60 mm/1 h,with a sensitivity of 81.4% and a specificity of 75.3%.The optimal predictive cutoff for PC was 243.00×10 9/L,with a sensitivity of 60.6% and a specificity of 71.8%.The optimal predictive cutoff for PC/MPV was 24.95,the sensitivity was 58.1% and the specificity was 74.1%.And the optimal predictive cutoff for PCT was 0.24%,with a sensitivity of 69.8% and a specificity of 63.5%. Conclusion:PC,PC to MPV ratio and PCT are of limited value to diagnose PJI.

Objective:To investigate the regulatory effect of blue light on the expression of brain derived neurotrophic factor (BDNF) in the habenula nucleus of depression-like rats induced by light deprivation.Methods:male SD rats were exposed to white light (white light control group, 20 rats) and constant darkness (depression model group, 60 rats), respectively. 18 days later rats in depression model group were randomly divided into three groups: depression model group (treated with constant darkness), blue light group (treated with blue light) and red light group (treated with red light). Rats in white light control group were kept in white light. All rats exposed to light were in a standard 12∶12 h Light/Dark condition at 20 lx for 36 days. Sucrose preference test was applied to evaluate depression-like symptoms of rats. The c-fos +cells in the habenula nucleus, intergeniculate leaflet and ventral lateral geniculate nucleus were detected. The phosphoylation of cAMP-response element binding protein (CREB) and the relative BDNF protein level in the habenula nucleus were measured. Results:Sucrose intake per kg body weight increased in rats exposed to blue light and returned to the level of control group ( P>0.05). Sucrose intake per kg body weight in red light group and depression model group were lower than control group ( P<0.05). More c-fos +cells were detected in the habenula nucleus, intergeniculate leaflet and ventral lateral geniculate nucleus from blue light group than those from depression model group ( P<0.05). The relative BDNF protein level and the phosphoylation of CREB in the habenula nucleus from blue light group were higher than those from depression model group ( P<0.05). Conclusion:Blue light could relieve depression-like symptoms in light-deprived rats. Exposure to blue light could activate neurons in the habenula nucleus to which intrinsically photosensitive retinal ganglion cells projected. Blue-light-mediated antidepressant effect might involve in the activation of CREB/BDNF signal transduction pathways in the habenula nucleus.

Model informed precision dosing (MIPD) is a new concept to guide precision dosing for individual patient by modeling and simulation based on the available information about the individual patient, medications and the disease. Compared to the empirical dosing, MIPD could improve the efficacy, safety, economics and adherence of the pharmacotherapy according to the individual's pathophysiology, genotyping and disease progression. This consensus report provides a brief account of the concept, methodology and implementation of MIPD as well as clinical decision supporting systems for MIPD. The status and future advancing of MIPD was also discussed to facilitate the appropriate application and development of MIPD in China.