Effect of sleep deprivation on expression of SIRT6 in cerebellum of immature mice / 中华麻醉学杂志

Objective:To evaluate the effect of sleep deprivation on the expression of sirtuin 6 (SIRT6) in the cerebellum of immature mice.Methods:Fifty SPF healthy male C57BL/6 mice, aged 4 weeks, weighing 14-16 g, were divided into 2 groups ( n=25 each) using a random number table method: control group (Con group) and sleep deprivation group (SD group). The chronic sleep deprivation model was prepared by using the multi-platform water environment method, with 20 h of sleep deprivation per day for 10 consecutive days. After sleep deprivation, a balance beam experiment was performed to test the balance and coordination ability of mice. The mice were sacrificed after anesthesia and cerebellar lobular IV-VI (4-6 cb) tissues were taken for microscopic examination of the ultrastructure (with a transmission electron microscope) and for determination of the dendritic spine density of cerebellar 4-6cb Purkinje neurons (by Golgi staining), co-expression of SIRT6 and Calbindin D-28k (CbD-28k) and expression of glucose transporter Glut3 of cerebellar 4-6cb (by immunofluorescence staining). Results:Compared with group Con, the duration of passage through the balance beam was significantly prolonged, and the number of posterior foot slips was increased, the synaptic gap of cerebellar 4-6cb neurons was increased, the thickness of postsynaptic density was increased, the density of dendritic spines of Purkinje cells and the number of positive cells co-expressing SIRT6 and CbD-28k were decreased, and the expression of Glut3 was down-regulated in group SD ( P<0.05). Conclusions:The mechanism by which sleep deprivation decreases the abilities of balance and coordination is related to down-regulating SIRT6 expression in cerebellar Purkinje cells and decreasing neuronal glucose metabolism, thus damaging the synaptic plasticity of cerebellum in immature mice.

Effect of propofol on parvalbumin neurons in medical prefrontal cortex of rats with social behavior disorders induced by chronic sleep deprivation / 中华麻醉学杂志

Objective:To evaluate the effect of propofol on parvalbumin (PV) neurons in the medical prefrontal cortex(mPFC)of rats with social behavior disorders induced by chronic sleep deprivation.Methods:Forty-two SPF male Sprague-Dawley rats, aged 8 weeks, weighing 200-250 g, were divided into 3 groups ( n=14 each) using a random number table method: control group (group Con), chronic sleep deprivation plus natural sleep group (group CSD+ NS), and chronic sleep deprivation plus propofol group (group CSD+ Pro). Sleep deprivation model was established by the modified multiple platform method, the rats were placed in the sleep-deprivation tank for 20 h a day (14: 00-10: 00), and allowed to sleep naturally for 4 h (10: 00-14: 00) a day for 28 consecutive days. Propofol 40 mg/kg was intraperitoneally injected for 28 consecutive days after sleep deprivation in CSD+ Pro group. While the equal volume of 10% fat emulsion was given in Con and CSD+ NS groups. After the end of sleep deprivation, a three-box social experiment was used to detect the social behavior of rats, and the number of the PV positive cells and density of the perineuronal network (PNN) in the mPFC area were measured by immunofluorescence. Results:Compared with group Con, the pertentage of rapid eye movement sleep and sniffing time preference coefficients for the strange rat 1 in the first stage and for the strange rat 2 in the second stage were significantly decreased, and the number of the PV positive cells and density of PNN in the mPFC area were decreased in group CSD+ NS ( P<0.05). Compared with group CSD+ NS, the sniffing time preference coefficients for the strange rat 1 in the first stage and for the strange rat 2 in the second stage were significantly increased, the number of the PV positive cells and density of PNN in the mPFC area were increased( P<0.05), and no significant change was found in the percentage of the rapid eye movement sleep in group CSD+ Pro. Conclusions:Propofol probably increases the number and function of PV neurons in the mPFC and ameliorates sleep deprivation-induced social behavior disorders in sleep-deprived rats.

Hepatitis B core-related antigen dynamics and risk of subsequent clinical relapses after nucleos(t)ide analog cessation

Background/Aims@#Finite nucleos(t)ide analog (NA) therapy has been proposed as an alternative treatment strategy for chronic hepatitis B (CHB), but biomarkers for post-treatment monitoring are limited. We investigated whether measuring hepatitis B core-related antigen (HBcrAg) after NA cessation may stratify the risk of subsequent clinical relapse (CR). @*Methods@#This retrospective multicenter analysis enrolled adults with CHB who were prospectively monitored after discontinuing entecavir or tenofovir with negative HBeAg and undetectable HBV DNA at the end of treatment (EOT). Patients with cirrhosis or malignancy were excluded. CR was defined as serum alanine aminotransferase > two times the upper limit of normal with recurrent viremia. We applied time-dependent Cox proportional hazard models to clarify the association between HBcrAg levels and subsequent CR. @*Results@#The cohort included 203 patients (median age, 49.8 years; 76.8% male; 60.6% entecavir) who had been treated for a median of 36.9 months (interquartile range [IQR], 36.5–40.1). During a median post-treatment follow-up of 31.7 months (IQR, 16.7–67.1), CR occurred in 104 patients with a 5-year cumulative incidence of 54.8% (95% confidence interval [CI], 47.1–62.4%). Time-varying HBcrAg level was a significant risk factor for subsequent CR (adjusted hazard ratio [aHR], 1.53 per log U/mL; 95% CI, 1.12–2.08) with adjustment for EOT HBsAg, EOT anti-HBe, EOT HBcrAg and time-varying HBsAg. During follow-up, HBcrAg <1,000 U/mL predicted a lower risk of CR (aHR, 0.41; 95% CI, 0.21–0.81). @*Conclusions@#Dynamic measurement of HBcrAg after NA cessation is predictive of subsequent CR and may be useful to guide post-treatment monitoring.

Evaluation of Malignancy Risk of Ampullary Tumors Detected by Endoscopy Using 2- 18FFDG PET/CT

Objective@#We aimed to investigate whether 2-[ 18F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (2-[ 18F]FDG PET/CT) can aid in evaluating the risk of malignancy in ampullary tumors detected by endoscopy. @*Materials and Methods@#This single-center retrospective cohort study analyzed 155 patients (79 male, 76 female; mean age, 65.7 ± 12.7 years) receiving 2-[ 18F]FDG PET/CT for endoscopy-detected ampullary tumors 5–87 days (median, 7 days) after the diagnostic endoscopy between June 2007 and December 2020. The final diagnosis was made based on histopathological findings. The PET imaging parameters were compared with clinical data and endoscopic features. A model to predict the risk of malignancy, based on PET, endoscopy, and clinical findings, was generated and validated using multivariable logistic regression analysis and an additional bootstrapping method. The final model was compared with standard endoscopy for the diagnosis of ampullary cancer using the DeLong test. @*Results@#The mean tumor size was 17.1 ± 7.7 mm. Sixty-four (41.3%) tumors were benign, and 91 (58.7%) were malignant. Univariable analysis found that ampullary neoplasms with a blood-pool corrected peak standardized uptake value in earlyphase scan (SUVe) ≥ 1.7 were more likely to be malignant (odds ratio [OR], 16.06; 95% confidence interval [CI], 7.13–36.18;P < 0.001). Multivariable analysis identified the presence of jaundice (adjusted OR [aOR], 4.89; 95% CI, 1.80–13.33; P = 0.002), malignant traits in endoscopy (aOR, 6.80; 95% CI, 2.41–19.20; P < 0.001), SUVe ≥ 1.7 in PET (aOR, 5.43; 95% CI, 2.00–14.72; P < 0.001), and PET-detected nodal disease (aOR, 5.03; 95% CI, 1.16–21.86; P = 0.041) as independent predictors of malignancy. The model combining these four factors predicted ampullary cancers better than endoscopic diagnosis alone (area under the curve [AUC] and 95% CI: 0.925 [0.874–0.956] vs. 0.815 [0.732–0.873], P < 0.001). The model demonstrated an AUC of 0.921 (95% CI, 0.816–0.967) in candidates for endoscopic papillectomy. @*Conclusion@#Adding 2-[ 18F]FDG PET/CT to endoscopy can improve the diagnosis of ampullary cancer and may help refine therapeutic decision-making, particularly when contemplating endoscopic papillectomy.

Research progress on liquid biopsy and its combination of radiology in diagnosis of pulmonary nodules / 中国胸心血管外科临床杂志

@#Lung cancer is a malignant tumor with the highest mortality worldwide, and its early diagnosis and evaluation have a crucial impact on the comprehensive treatment of patients. Early preoperative diagnosis of lung cancer depends on a variety of imaging and tumor marker indicators, but it cannot be accurately assessed due to its high false positive rate. Liquid biopsy biomarkers can detect circulating tumor cells and DNA in peripheral blood by non-invasive methods and are gradually becoming a powerful diagnostic tool in the field of precision medicine for tumors. This article reviews the research progress of liquid biopsy biomarkers and their combination with clinical imaging features in the early diagnosis of lung cancer.

A prospective study on application of human umbilical cord mesenchymal stem cells combined with autologous Meek microskin transplantation in patients with extensive burns / 中华烧伤杂志

Objective: To investigate the effects of human umbilical cord mesenchymal stem cells (hUCMSCs) combined with autologous Meek microskin transplantation on patients with extensive burns. Methods: The prospective self-controlled study was conducted. From May 2019 to June 2022, 16 patients with extensive burns admitted to the 990th Hospital of PLA Joint Logistics Support Force met the inclusion criteria, while 3 patients were excluded according to the exclusion criteria, and 13 patients were finally selected, including 10 males and 3 females, aged 24-61 (42±13) years. A total of 20 trial areas (40 wounds, with area of 10 cm×10 cm in each wound) were selected. Two adjacent wounds in each trial area were divided into hUCMSC+gel group applied with hyaluronic acid gel containing hUCMSCs and gel only group applied with hyaluronic acid gel only according to the random number table, with 20 wounds in each group. Afterwards the wounds in two groups were transplanted with autologous Meek microskin grafts with an extension ratio of 1∶6. In 2, 3, and 4 weeks post operation, the wound healing was observed, the wound healing rate was calculated, and the wound healing time was recorded. The specimen of wound secretion was collected for microorganism culture if there was purulent secretion on the wound post operation. In 3, 6, and 12 months post operation, the scar hyperplasia in wound was assessed using the Vancouver scar scale (VSS). In 3 months post operation, the wound tissue was collected for hematoxylin-eosin (HE) staining to observe the morphological changes and for immunohistochemical staining to observe the positive expressions of Ki67 and vimentin and to count the number of positive cells. Data were statistically analyzed with paired samples t test and Bonferronni correction. Results: In 2, 3, and 4 weeks post operation, the wound healing rates in hUCMSC+gel group were (80±11)%, (84±12)%, and (92±9)%, respectively, which were significantly higher than (67±18)%, (74±21)%, and (84±16)% in gel only group (with t values of 4.01, 3.52, and 3.66, respectively, P<0.05). The wound healing time in hUCMSC+gel group was (31±11) d, which was significantly shorter than (36±13) d in gel only group (t=-3.68, P<0.05). The microbiological culture of the postoperative wound secretion specimens from the adjacent wounds in 2 groups was identical, with negative results in 4 trial areas and positive results in 16 trial areas. In 3, 6, and 12 months post operation, the VSS scores of wounds in gel only group were 7.8±1.9, 6.7±2.1, and 5.4±1.6, which were significantly higher than 6.8±1.8, 5.6±1.6, and 4.0±1.4 in hUCMSC+gel group, respectively (with t values of -4.79, -4.37, and -5.47, respectively, P<0.05). In 3 months post operation, HE staining showed an increase in epidermal layer thickness and epidermal crest in wound in hUCMSC+gel group compared with those in gel only group, and immunohistochemical staining showed a significant increase in the number of Ki67 positive cells in wound in hUCMSC+gel group compared with those in gel only group (t=4.39, P<0.05), with no statistically significant difference in the number of vimentin positive cells in wound between the 2 groups (P>0.05). Conclusions: The application of hyaluronic acid gel containing hUCMSCs to the wound is simple to perform and is therefore a preferable route. Topical application of hUCMSCs can promote healing of the autologous Meek microskin grafted area in patients with extensive burns, shorten wound healing time, and alleviate scar hyperplasia. The above effects may be related to the increased epidermal thickness and epidermal crest, and active cell proliferation.

Predictive value of three kinds of thrombosis risk assessment scale for lower extremity deep vein thrombosis after hip fracture in elderly patients / 中国骨伤

OBJECTIVE@#To explore predictive value of Caprini score, Wells score and Autar score for lower extremity deep vein thrombosis (DVT) after hip fracture in elderly patients.@*METHODS@#A total of 310 elderly patients with hip fracture were selected from January 2018 to September 2022. According to the lower extremity color ultrasound examination results, 155 patients with DVT were divided into thrombosis group, included 42 males and 113 females, aged from 60 to 101 years old with an average of (80.58±8.84) years old; and 155 patients without DVT were divided into control group, included 58 males and 97 females, aged from 60 to 94 years old with an average of (79.01±8.99) years old. Caprini score, Wells score and Autar score immediately after admission were collected and compared between two groups. Receiver operating characteristic (ROC) curve was used to evaluate predictive value of three thrombus risk assessment tables for DVT after hip fracture in elderly patients.@*RESULTS@#Caprini score, Wells score and Autar score in thrombus group were significantly higher than those in control group (P<0.001). ROC curve analysis results showed that the best cut-off value of Caprini score was 8.5 points, the sensitivity was 46.5%, the specificity was 99.4%, and area under the curve(AUC) was 0.763. The best cut-off value of Wells score was 1.5, the sensitivity was 100%, the specificity was 99.4%, and AUC was 0.998. The best cut-off value of Autar score was 10.5 points, the sensitivity was 58.1%, the specificity was 84.5%, and AUC was 0.717.@*CONCLUSION@#Caprini scale, Wells scale and Autar scale all have good predictive efficacy for the risk of DVT in elderly patients with hip fracture, and could provide an important reference for clinical guidance for prevention, management and treatment of DVT after hip fracture in elderly patients, among which Wells scale has a higher predictive value.

Efficacy of low-intensity pulsed ultrasound therapy in elderly patients with coronary heart disease and angina pectoris / 中华老年医学杂志

Objective:To investigate the practical efficacy of low-intensity pulsed ultrasound(LIPUS)and its effects on hemodynamics in patients with coronary heart disease and angina pectoris.Methods:As a single-center randomized controlled study, 66 elderly patients with coronary heart disease and angina pectoris treated at Qilu Hospital of Shandong University between November 2021 and August 2022 were consecutively recruited.Participants were divided into an ultrasound group and a control group via the random number table method, with 33 in each group.Both groups were given conventional drug treatment, and the ultrasound group was supplemented with LIPUS treatment.After 20 sessions of treatment, the clinical efficacy, blood lipid levels, inflammatory factors and hemodynamics from noninvasive monitoring before and after treatment were compared.Results:There were no statistically significant differences in baseline data between the two groups( P>0.05). After treatment, marked effectiveness was seen in 12 cases(36.4%), effectiveness in 18 cases(54.5%), ineffectiveness in 2 cases(6.1%)and aggravation in 1 case(3%)in the ultrasound group, with a total effectiveness rate of 90.9 %.In the control group, marked effectiveness was seen 2 cases(6.1%), effectiveness in 19 cases(57.6%)and ineffectiveness in 9 cases(27.3%), with a total effectiveness rate of 63.6%.Statistically significant favorable results were achieved in the ultrasound treatment group, compared with the control group( P<0.05). Also, compared with the control group, patients in the ultrasound group showed lower total cholesterol[(2.31±1.03)mmol/L vs.(4.36±0.76)mmol/L, P<0.01], decreased low-density lipoprotein cholesterol[(1.24±0.70)mmol/L vs.(1.74±0.44)mmol/L, P<0.01], decreased triglycerides[(1.04±0.40)mmol/L vs.(1.28±0.49)mmol/L, P<0.05], decreased apolipoprotein B[(0.67±0.25)g/L vs.(0.90±0.14)g/L, P<0.01], decreased interleukin-6[(2.87±2.52)ng/L vs.(4.66±3.30)ng/L, P<0.05], and decreased high-sensitivity C-reactive protein[(1.04±1.41)mg/L vs.(3.80±5.78)mg/L, P<0.05]. Concerning hemodynamics, there was an increase in cardiac output[(4.92±1.05)L/min vs.(4.39±0.97)L/min, P<0.05], stroke volume[(75.85±17.50)ml/beat vs.(66.97±15.57)ml/beat, P<0.05], cardiac index[(37.50±7.14)ml·beat -1·m -2vs.(43.29±7.96)ml·beat -1·m -2, P<0.01], and stroke volume index[(3.05±0.45)L/min 2vs.(2.51±0.43)L/min 2, P<0.01], but a decrease in systemic vascular resistance[(1 358.29±325.23)dyne·s -1·cm -5vs.(1 617.94±526.27)dyne·s -1·cm -5, P<0.05], total vascular resistance[(4.07±24.30)% vs.(21.32±31.94)%, P<0.05], and average heart rate[(63.43±7.42)beats/min vs.(69.11±10.89)beats/min, P<0.05]. Conclusions:LIPUS treatment can improve symptoms, blood lipid profiles, inflammatory factors and hemodynamics in patients with coronary heart disease and angina pectoris.It is a safe and effective adjuvant therapy for elderly patients with coronary heart disease and angina pectoris.

Comparison of effects of desflurane versus sevoflurane anesthesia on sleep quality of sleep-deprived mice / 中华麻醉学杂志

Objective:To compare the effects of desflurane and sevoflurane anesthesia on the sleep quality of sleep-deprived mice.Methods:Thirty-two clean-grade healthy male C57BL/6 mice, aged 10 weeks, weighing 20-25 g, were divided into 4 groups ( n=8 each) by the random number table method: control group (C group), sleep deprivation group (SD group), sleep deprivation+ sevoflurane group (SD+ SEV group), and sleep deprivation+ desflurane group (SD+ DES group). In the four groups, EEG-EMG electrodes were implanted for recording EEG and EMG, and sleep deprivation model was developed by the gentle stimulation method with a brush for 12 h (6: 00-18: 00) after 7 days of adaptation. The 6 h after sleep deprivation was divided into 2 time periods: T 1 period (18: 00-20: 00) and T 2 period (20: 00-24: 00). T 1 period In SD group, mice were allowed ad libitum recovery sleep after sleep deprivation. C group and SD group were exposed to 60% oxygen 1.5 L/min. In SD+ DES group and SD+ SEV group, mice were exposed to 6% desflurane and 2.5% sevoflurane, respectively, for 2 h in 60% oxygen 1.5 L/min following sleep deprivation. T 2 period Four groups were allowed ad libitum recovery sleep with the EEG-EMG signal recording. The percentages and number of wakefulness time, rapid eye movement time and non-rapid eye movement time during each time period were calculated using Lunion Data software. Results:Compared with C group, the percentage of non-rapid eye movement time and the percentage of rapid eye movement time were significantly decreased, and the percentage of wakefulness time was increased during 12 h sleep deprivation in SD group, SD+ SEV group and SD+ DES group ( P<0.05). Compared with T 1 period, the percentage of non-rapid eye movement time was significantly increased, and the percentage of wakefulness time and percentage of rapid eye movement time were decreased in T 2 period in SD group ( P<0.05). Compared with SD group, the percentage of non-rapid eye movement time and percentage of rapid eye movement time were significantly decreased, and the percentage of wakefulness time was increased in T 2 period in SD+ SEV group and SD+ DES group ( P<0.05). There was no significant difference in the percentage of non-rapid eye movement, rapid eye movement and wakefulness time in T 2 period between SD+ SEV group and SD+ DES group ( P>0.05). Compared with SD+ SEV group, the number of non-rapid eye movement in T 2 period was significantly reduced in SD+ DES group ( P<0.05). Conclusions:The effect of desflurane anesthesia in improving sleep quality is better than sevoflurane anesthesia in sleep-deprived mice.

Role of activation of VGLUT2 neurons in vagal nodose ganglion in dexmedetomidine-caused bradycardia in mice / 中华麻醉学杂志

Objective:To evaluate the role of activation of vesicular glutamate transporter 2 (VGLUT2) neurons in vagal nodose ganglion in dexmedetomidine-caused bradycardia in mice.Methods:Ninety-six SPF healthy male VGLUT2-cre mice, aged 10 weeks, weighing 20-25 g, were divided into 6 groups ( n=16 each) by the random number table method: normal saline control group (NS group), dexmedetomidine group (Dex group), viral control + chemogenetic control + dexmedetomidine group (eGFP-NS+ Dex group), viral transfection + chemogenetic control + dexmedetomidine group (hM4Di-NS+ Dex group), viral control + chemogenetic inhibition + dexmedetomidine group (eGFP-CNO+ Dex group) and viral transfection + chemogenetic inhibition + dexmedetomidine group (hM4Di-CNO+ Dex group). Dexmedetomidine 100 μg/kg was intraperitoneally injected in Dex group. The equal volume of normal saline was intraperitoneally injected in NS group. AAV2/9-hSyn-DIO-hM4Di-eGFP was injected in the right nodose ganglion in hM4Di-NS+ Dex group and hM4Di-CNO+ Dex group, and AAV2/9-hSyn-DIO-eGFP was injected in the right nodose ganglion in eGFP-NS+ Dex group and eGFP-CNO+ Dex group, allowing the virus expression for 21 days. On the 22nd day after virus injection, clozapine-n-oxide (CNO) 5 mg/kg was intraperitoneally injected in hM4Di-CNO+ Dex group and eGFP-CNO+ Dex group, the equal volume of normal saline was intraperitoneally injected in hM4Di-NS+ Dex group and eGFP-NS+ Dex group, 1 h later the efficacy of CNO reached the peak, and then dexmedetomidine 100 μg/kg was intraperitoneally injected. The respiratory rate, heart rate, SpO 2 and discharge frequency of the right vagal nodose ganglion were synchronously measured by multi-channel electrophysiology in vivo. The expression of phosphorylated extracellular signal-regulated kinase (pERK) and VGLUT2 and co-expression of pERK and VGLUT2 in the right vagal nodose ganglion were detected by immunofluorescence assay. Results:Compared with NS group, the percentage of heart rate variation and neuron firing frequency after administration were significantly increased, and pERK expression was up-regulated in the other five groups ( P<0.05). Compared with Dex group, the percentage of heart rate variation and neuron firing frequency after administration were significantly decreased, and pERK expression was down-regulated in hM4Di-CNO+ Dex group, and no significant change was found in the parameters mentioned above in hM4Di-NS+ Dex group, eGFP-NS+ Dex group and eGFP-CNO+ Dex group ( P>0.05). Compared with hM4Di-CNO+ Dex group, the percentage of heart rate variation and neuron firing frequency after administration were significantly increased, and pERK expression was up-regulated in eGFP-CNO+ Dex group ( P<0.05). There was no significant difference in the percentage of respiratory variation and SpO 2 among the six groups ( P>0.05). The expression of VGLUT2-positive neurons was abundant in nodose ganglia, and the co-expression rate of pERK and VGLUT2 was nearly 90%. The co-expression rate of pERK and VGLUT2 decreased to about 30% after inhibition of VGLUT2 neurons in ganglion. Conclusions:The mechanism by which dexmedetomidine causes bradycardia is associated with activation of VGLUT2 neurons in vagal nodose ganglia in mice.

Circulating tumor cells-based model for pulmonary solid nodules diagnosis: a multicenter study / 中华胸心血管外科杂志

Objective:To evaluate the clinical radiological features combined with circulating tumor cells in the diagnosis of benign and malignant pulmonary solid nodules.Methods:Clinical data of 437 patients from Shanghai Pulmonary Hospital(SPH cohort) from January to April 2021 and 82 patients from Lanzhou University First Hospital (LZH cohort) from August 2019 to May 2022 were retrospectively included. Patients in Shanghai pulmonary hospital were randomly divided into training set and internal validation set in a ratio of 4∶1 by random number table method and patients in Lanzhou University First Hospital were as external validation set. Independent risk factors were selected by regression analysis of training set constructed a Nomogram prediction model. The performance of the Nomogram prediction model was estimated by applying receiver operating curve( ROC) analysis, tested in different nodules size and intermediate risk IPSNs and tested by calibration curve. Results:Independent risk factors selected by regression analysis for solid pulmonary nodules were age, the level of CTC, pleural Indentation, lobulation, spiculation. The Nomogram prediction mode provided an area under ROC( AUC) of 0.888, 0.833 in internal validation set and external validation set, outperforming radiological features model(0.835, P=0.007; 0.804, P=0.043) Mayo clinical model(0.781, P=0.019; 0.726, P=0.033) and CTCs(0.699, P=0.002; 0.648, P=0.012) in both two validation sets, C-index of 0.888, 0.871 and corrected C-index of 0.853, 0.842 in both two validation sets . The AUC of the prediction model with internal validation set was 0.905 and 0.871 for nodule diameter of 5-20 mm and intermediate risk probability. Conclusion:The prediction model in this study has better diagnostic value and practicability, and is more effective in clinical diagnosis of diseases.

Risk analysis of perioperative outcomes of lung transplantation and the prediction of delayed extubation / 中华器官移植杂志

Objective:To explore the risk factors of perioperative outcomes of lung transplantation and establish a predictive model for delayed extubation after lung transplantation.Methods:From January 1, 2020 to December 31, 2022, 104 lung transplantation recipients were retrospectively collected to identify the risk factors of early post-operative outcome.According to the timing of extubation post-lung transplantation, they were assigned into two groups of normal(77 cases)and delayed(27 cases). Baseline profiles, type of primary diagnosis, cold ischemic duration and lung transplantation approach were compared between two groups.The factors with significant difference were examined by univariate and multivariate Logistic regression.Furthermore, multivariate logistic model was visualized by a nomogram.Receiver operating characteristic(ROC)curve and decision curve analysis(DCA) were performed for evaluating the model's predictive performance and its value for clinical utilization.Results:The postoperative mortality rate was 9.6%.Delayed extubation was a strong predictor for postoperative mortality.Cold ischemic time outperformed others variates in terms of delayed extubation prediction.AUC of cold ischemic time and multivariate logistic model was 0.75(95% CI: 0.69-0.81)and 0.87(95% CI: 0.82-0.91). Conclusions:Delayed postoperative extubation is a key predictor of early post-lung transplantation mortality.The established predictive model may effectively identify high-risk patients for preventive intervention and survival improvement post-lung transplantation.

Network meta-analysis of the efficacy and safety of different drug regimens in the treatment of children with Kawasaki disease / 中国药房

OBJECTIVE To evaluate the efficacy and safety of different drug regimens in the treatment of children with Kawasaki disease， and to provide evidence-based reference for clinical treatment. METHODS Retrieved from the Cochrane Library， Medline， Embase， CINAHL， Web of Science， ProQuest， Google Scholar， CNKI， Wanfang Data， Baidu academic database， World Health Organization International Clinical Trials Registration Platform and ClinicalTrials. gov， randomized controlled trials （RCTs） about intravenous immunoglobulin （IVIG）+glucocorticoid or cyclosporine or tumor necrosis factor-alpha （TNF-α） blocker （trial group） versus standard IVIG therapy （control group） were collected from the establishment of the database to Feb. 28th， 2023. After screening the literature， extracting data， and evaluating the quality of the literature， Stata 14.2 software was used for network meta-analysis. RESULTS Ten RCTs with a total of 1 323 participants involving six measures were included： standard IVIG therapy， glucocorticoid therapy，cyclosporine therapy， TNF- α blocker therapy， remedial glucocorticoid therapy and remedial TNF- α blocker therapy. Results of network meta-analysis showed that the incidence of coronary artery aneurysms （CAA） at 4-8 weeks was significantly lower in patients receiving glucocorticoid therapy than receiving standard IVIG therapy and TNF-α blocker therapy. The incidences of CAA at 4-8 weeks in children treated with remedial glucocorticoid therapy and remedial TNF- α blocker therapy were significantly higher than those treated with glucocorticoid therapy； there was no significant difference in the incidence of CAA at 4-8 weeks among other interventions （P＞ 0.05）； network meta-order of the incidence was glucocorticoid therapy＜cyclosporine therapy＜standard IVIG therapy＜remedial TNF-α blocker therapy＜remedial glucocorticoid therapy＜TNF-α blocker therapy. The incidence of initial IVIG resistance in children receiving cyclosporine therapy was significantly lower than those receiving standard IVIG therapy； there was no significant difference in the incidence of initial IVIG resistance among other interventions （P＞0.05）； network meta-order of the incidence was cyclosporine therapy＜glucocorticoid therapy＜TNF-α blocker therapy＜standard IVIG therapy. There was no significant difference in the incidence of ADR among different interventions （P＞0.05）； network meta-order of the incidence was remedial TNF-α blocker therapy＜TNF-α blocker therapy＜standard IVIG therapy＜glucocorticoid therapy＜cyclosporine therapy. CONCLUSIONS Glucocorticoid therapy at the initial treatment can significantly reduce the risk of CAA at 4-8 weeks in children with Kawasaki disease； cyclosporine has a significant effect on improving initial IVIG resistance， and the use of TNF-α blocker in the remedial stage may have the lowest incidence of adverse reactions.

Teriparatide treatment shows faster healing than sacroplasty for postmenopausal women with sacral insufficiency fracture

Objectives@#Sacral insufficiency fracture (SIF) is not an uncommon osteoporosis fracture among the elderly. Aside from traditional treatments, sacroplasty and teriparatide (TPTD) injection have been introduced. This report aims to compare the effects of sacroplasty and teriparatide on clinical outcomes of SIF. @*Methods@#Thirty-one elderly patients with SIF were enrolled in this retrospective observational study. Four male patients were excluded. Fourteen patients who received TPTD for 6 months were classified into the TPTD group (TT), and 13 who underwent sacroplasty were classified into the sacroplasty group (SS). All patients in both groups were instructed to take calcium and vitamin D supplements daily. Their symptoms and signs, visual analog score (VAS), Oswestry disability index (ODI), and radiographic studies were retrospectively reviewed. @*Results@#The TT group showed significantly lower VAS than SS group after 3 (P < 0.001) and 6 months of treatment (P < 0.001). The TT group also has significant lower ODI than SS group after 1 (P = 0.010), 3 (P = 0.005) and 6 months (P < 0.001) of treatment. Upon generalized estimating equations (GEE) analysis, the TT group showed significantly more reduction in both VAS and ODI compared to the SS group at 1 month (P = 0.022, P = 0.001), 3 months (P < 0.001, P < 0.001), and 6 months (P < 0.001, P < 0.001) post-treatment. @*Conclusions@#Postmenoposal woman with SIF who received TPTD healed better than those who underwent sacroplasty after 1 month treatment.

Application value of radiomics-based machine learning model in identifying the degree of pulmonary ground-glass nodule infiltration / 中国胸心血管外科临床杂志

@#Objective    To establish a machine learning model based on computed tomography (CT) radiomics for preoperatively predicting invasive degree of lung ground-glass nodules (GGNs). Methods    We retrospectively analyzed the clinical data of GGNs patients whose solid component less than 3 cm in the Department of Thoracic Surgery of Shanghai Pulmonary Hospital from March 2021 to July 2021 and the First Hospital of Lanzhou University from January 2019 to May 2022. The lesions were divided into pre-invasiveness and invasiveness according to postoperative pathological results, and the patients were randomly divided into a training set and a test set in a ratio of 7∶3. Radiomic features (1 317) were extracted from CT images of each patient, the max-relevance and min-redundancy (mRMR) was used to screen the top 100 features with the most relevant categories, least absolute shrinkage and selection operator (LASSO) was used to select radiomic features, and the support vector machine (SVM) classifier was used to establish the prediction model. We calculated the area under the curve (AUC), sensitivity, specificity, accuracy, negative predictive value, positive predictive value to evaluate the performance of the model, drawing calibration and decision curves of the prediction model to evaluate the accuracy and clinical benefit of the model, analyzed the performance in the training set and subgroups with different nodule diameters, and compared the prediction performance of this model with Mayo and Brock models. Two primary thoracic surgeons were required to evaluate the invasiveness of GGNs to investigate the clinical utility of the mode. Results    A total of 400 patients were divided into the training set (n=280) and the test set (n=120) according to the admission criteria. There were 267 females and 133 males with an ……

Clinical efficacy and learning curve of robot-assisted thymectomy via subxiphoid approach / 中国胸心血管外科临床杂志

@#Objective     To explore the clinical efficacy and learning curve of robot-assisted thymectomy via subxiphoid approach. Methods    The clinical data of patients with robot-assisted thymectomy surgery via subxiphoid approach performed by the same surgical team in the Department of Thoracic Surgery of Shanghai Pulmonary Hospital from February 2021 to August 2022 were retrospectively analyzed. The cumulative sum (CUSUM) analysis and best fit curve were used to analyze the learning curve of this surgery. The general information and perioperative indicators of patients at different learning stages were compared to explore the impact of different learning stages on clinical efficacy of patients. Results    A total of 67 patients were enrolled, including 31 males and 36 females, aged 57.10 (54.60, 59.60) years. The operation time was 117.00 (87.00, 150.00) min. The best fitting equation of CUSUM learning curve was y=0.021 2x3–3.192 5x2 +120.17x–84.444 (x was the number of surgical cases), which had a high R2 value of 0.977 8, and the fitting curve reached the top at the 25th case. Based on this, the learning curve was divided into a learning period and a proficiency period. The operation time and intraoperative blood loss in the proficiency stage were significantly shorter or less than those in the learning stage (P<0.001), and there was no statistical difference in thoracic drainage time and volume between the two stages (P>0.05). Conclusion    The learning process of robot-assisted thymectomy via subxiphoid approach is safe, and this technique can be skillfully mastered after 25 cases.

A novel biodegradable polymer-coated sirolimus-eluting stent: 1-year results of the HELIOS registry / 中华医学杂志(英文版)

BACKGROUND@#The HELIOS stent is a sirolimus-eluting stent with a biodegradable polymer and titanium oxide film as the tie-layer. The study aimed to evaluate the safety and efficacy of HELIOS stent in a real-world setting.@*METHODS@#The HELIOS registry is a prospective, multicenter, cohort study conducted at 38 centers across China between November 2018 and December 2019. A total of 3060 consecutive patients were enrolled after application of minimal inclusion and exclusion criteria. The primary endpoint was target lesion failure (TLF), defined as a composite of cardiac death, non-fatal target vessel myocardial infarction (MI), and clinically indicated target lesion revascularization (TLR) at 1-year follow-up. Kaplan-Meier methods were used to estimate the cumulative incidence of clinical events and construct survival curves.@*RESULTS@#A total of 2998 (98.0%) patients completed the 1-year follow-up. The 1-year incidence of TLF was 3.10% (94/2998, 95% closed interval: 2.54-3.78%). The rates of cardiac death, non-fatal target vessel MI and clinically indicated TLR were 2.33% (70/2998), 0.20% (6/2998), and 0.70% (21/2998), respectively. The rate of stent thrombosis was 0.33% (10/2998). Age ≥60 years, diabetes mellitus, family history of coronary artery disease, acute myocardial infarction at admission, and device success were independent predictors of TLF at 1 year.@*CONCLUSION@#The 1-year incidence rates of TLF and stent thrombosis were 3.10% and 0.33%, respectively, in patients treated with HELIOS stents. Our results provide clinical evidence for interventional cardiologists and policymakers to evaluate HELIOS stent.@*CLINICAL TRIAL REGISTRATION@#ClinicalTrials.gov, NCT03916432.

Wedge Resection of Pulmonary Nodules (≤2 cm): A Consensus Statement by Specialists of Thoracic Surgery (2023 Edition) / 中国肺癌杂志

Lung cancer is the highest cancer-related mortality rate in the world, and is one of the most common malignancies. The standard treatment for early-stage non-small cell lung cancer (NSCLC) is radical lobectomy, while recent studies have found that sub-lobectomy of pulmonary nodules (≤2 cm) is not inferior to lobectomy and even improve the prognosis of the patients. These important findings will effectively and positively promote the formation of consensus and principles of wedge resection of pulmonary nodules (≤2 cm) in the field of thoracic surgery. The purpose of this study is to present a national expert consensus on wedge resection of pulmonary nodules (≤2 cm) in the field of thoracic surgery. The experts from Editorial Committee of Consensus on Wedge Resection of Lung Nodules (≤2 cm) (2023 Edition) jointly participated in the revision work. According to the clinical progress about the wedge resection of pulmonary nodules (≤2 cm) at home and abroad during recent years, experts jointly wrote Wedge Resection of Pulmonary Nodules (≤2 cm): a Consensus Statement by Specialists of Thoracic Surgery (2023 Edition), in combination with the homogeneous treatment principles of wedge resection in the field of thoracic surgery in China. This consensus was summarized from the following aspects: (1) Indications of wedge resection of pulmonary nodules (≤2 cm); (2) Resection range of pulmonary nodules (≤2 cm) required for wedge resection; (3) Excisable pulmonary nodules (≤2 cm) for wedge resection. This consensus finally put forward 8 recommended opinions, and sorted out 5 opinions which were still controversial and needed more evidence. The integrated opinions were generated through the discussion held among the experts of thoracic surgery from all over the country, making wedge resection of pulmonary nodules (≤2 cm) more appropriate for China and more standardized and homogeneous for clinical practice. In the future, more relevant researches should be accumulated based on the characteristics of lung cancer and its diagnosis and treatment in China, optimizing the treatment of pulmonary nodules (≤2 cm).

Disrupted Maturation of Prefrontal Layer 5 Neuronal Circuits in an Alzheimer's Mouse Model of Amyloid Deposition / 神经科学通报·英文版

Mutations in genes encoding amyloid precursor protein (APP) and presenilins (PSs) cause familial forms of Alzheimer's disease (AD), a neurodegenerative disorder strongly associated with aging. It is currently unknown whether and how AD risks affect early brain development, and to what extent subtle synaptic pathology may occur prior to overt hallmark AD pathology. Transgenic mutant APP/PS1 over-expression mouse lines are key tools for studying the molecular mechanisms of AD pathogenesis. Among these lines, the 5XFAD mice rapidly develop key features of AD pathology and have proven utility in studying amyloid plaque formation and amyloid β (Aβ)-induced neurodegeneration. We reasoned that transgenic mutant APP/PS1 over-expression in 5XFAD mice may lead to neurodevelopmental defects in early cortical neurons, and performed detailed synaptic physiological characterization of layer 5 (L5) neurons from the prefrontal cortex (PFC) of 5XFAD and wild-type littermate controls. L5 PFC neurons from 5XFAD mice show early APP/Aβ immunolabeling. Whole-cell patch-clamp recording at an early post-weaning age (P22-30) revealed functional impairments; although 5XFAD PFC-L5 neurons exhibited similar membrane properties, they were intrinsically less excitable. In addition, these neurons received smaller amplitude and frequency of miniature excitatory synaptic inputs. These functional disturbances were further corroborated by decreased dendritic spine density and spine head volumes that indicated impaired synapse maturation. Slice biotinylation followed by Western blot analysis of PFC-L5 tissue revealed that 5XFAD mice showed reduced synaptic AMPA receptor subunit GluA1 and decreased synaptic NMDA receptor subunit GluN2A. Consistent with this, patch-clamp recording of the evoked L23>L5 synaptic responses revealed a reduced AMPA/NMDA receptor current ratio, and an increased level of AMPAR-lacking silent synapses. These results suggest that transgenic mutant forms of APP/PS1 overexpression in 5XFAD mice leads to early developmental defects of cortical circuits, which could contribute to the age-dependent synaptic pathology and neurodegeneration later in life.

A phase I study of subcutaneous envafolimab (KN035) monotherapy in Chinese patients with advanced solid tumors / 中华肿瘤杂志

Objective: To evaluate the safety and antitumor activity of envafolimab monotherapy in Chinese patients with advanced solid tumors. Methods: This open-label, multicenter phase I trial included dose escalation and dose expansion phases. In the dose escalation phase, patients received subcutaneous 0.1, 0.3, 1.0, 2.5, 5.0 or 10.0 mg/kg envafolimab once weekly (QW) following a modified "3+ 3" design. The dose expansion phase was performed in the 2.5 mg/kg and 5.0 mg/kg (QW) dose cohorts. Results: At November 25, 2019, a total of 287 patients received envafolimab treatment. During the dose escalation phase, no dose-limiting toxicities (DLT) was observed. In all dose cohorts, drug-related treatment-emergent adverse events (TEAEs) for all grades occurred in 75.3% of patients, and grade 3 or 4 occurred in 20.6% of patients. The incidence of immune-related adverse reactions (irAE) was 24.0% for all grades, the most common irAEs (≥2%) included hypothyroidism, hyperthyroidism, immune-associated hepatitis and rash. The incidence of injection site reactions was low (3.8%), all of which were grades 1-2. Among the 216 efficacy evaluable patients, the objective response rate (ORR) and disease control rate (DCR) were 11.6% and 43.1%, respectively. Median duration of response was 49.1 weeks (95% CI: 24.0, 49.3). Pharmacokinetic (PK) exposure to envafolimab is proportional to dose and median time to maximum plasma concentration is 72-120 hours based on the PK results from the dose escalation phase of the study. Conclusion: Subcutaneous envafolimab has a favorable safety and promising preliminary anti-tumor activity in Chinese patients with advanced solid tumors.