Objective:To investigate the effect of methylene blue (MB) on motor dysfunction and its mechanism in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mouse models.Methods:Forty healthy male C57BL/6 mice were randomly divided into 4 groups: control group, model group, low-dose treatment group and medium-dose treatment group ( n=10); PD mouse models were established by intraperitoneal injection of 25 mg/kg/d MPTP for a consecutive 7 d; low-dose treatment group and medium-dose treatment group were pretreated intraperitoneally with MB 2 mg/kg/d or MB 10 mg/kg/d for a consecutive 3 d, respectively; and then, MPTP 25 mg/kg/d+MB 2 mg/kg/d or MPTP 25 mg/kg/d+MB 10 mg/kg/d were injected intraperitoneally into the low-dose treatment group or medium-dose treatment group for a consecutive 7 d (MPTP and MB were given at 12 h of interval). Eight d after modeling, open field experiment, pole climbing experiment and rod rotating experiment were carried out to evaluate the spontaneous movement, coordination, endurance and motor ability. And then, the mice were sacrificed; immunofluorescent staining was used to observe tyrosine hydroxylase (TH) expression in the substantia nigra; Western blotting was used to detect the expressions of TH, α-synuclein, nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), cleaved-Caspase-1 and Gasdermin D (GSDMD) in the striatum and substantia nigra of mice. Contents of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-18 in the substantia nigra and striatum of mice were detected by ELISA. Results:Compared with the control group, the model group had shortened residence time in rod rotating, prolonged descent time in rod climbing, reduced total movement distance in open field, decreased number of TH-positive cells in the substania nigra, decreased TH protein levels in the substania nigra and striatum, and increased NLRP3, ASC, cleaved-Caspase-1, GSDMD and GSDMD-N protein levels in the substania nigra and striatum, and increased TNF-α, IL-1β and IL-18 contents in the substania nigra and striatum, with significant differences ( P<0.05). Compared with the model group, low-dose treatment group and medium-dose treatment group had prolonged residence time in rod rotating, shortened descent time in rod climbing, increased total movement distance in open field, increased number of TH-positive cells in the substania nigra, and increased TH protein levels in the substania nigra and striatum, decreased NLRP3, ASC, and cleaved-Caspase-1 levels in the substania nigra and striatum, and decreased TNF-α, IL-1β and IL-18 contents in the substania nigra and striatum, with significant differences ( P<0.05). No statistical differences in the above indexes were noted between the low-dose treatment group and medium-dose treatment group ( P>0.05). Conclusion:Low-/medium-dose MB can ameliorate motor dysfunction in PD mouse models, whose mechanism may be related to downregulate NLRP3 inflammasome and inhibit neuroinflammatory response to reduce dopaminergic neuron pyroptosis.

OBJECTIVE: To develop and validate a mechanical power (MP)-oriented nomogram prediction model of weaning failure in mechanically ventilated patients. METHODS: Patients who underwent invasive mechanical ventilation (IMV) for more than 24 hours and were weaned using a T-tube ventilation strategy were collected from the Medical Information Mart for Intensive Care-IV v1.0 (MIMIC-IV v1.0) database. Demographic information and comorbidities, respiratory mechanics parameters 4 hours before the first spontaneous breathing trial (SBT), laboratory parameters preceding the SBT, vital signs and blood gas analysis during SBT, length of intensive care unit (ICU) stay and IMV duration were collected and all eligible patients were enrolled into the model group. Lasso method was used to screen the risk factors affecting weaning outcomes, which were included in the multivariate Logistic regression analysis. R software was used to construct the nomogram prediction model and build the dynamic web page nomogram. The discrimination and accuracy of the nomogram were assessed by receiver operator characteristic curve (ROC curve) and calibration curves, and the clinical validity was assessed by decision curve analysis (DCA). The data of patients undergoing mechanical ventilation hospitalized in ICU of the First People's Hospital of Lianyungang City and the Second People's Hospital of Lianyungang City from November 2021 to October 2022 were prospectively collected to externally validate the model. RESULTS: A total of 3 695 mechanically ventilated patients were included in the model group, and the weaning failure rate was 38.5% (1 421/3 695). Lasso regression analysis finally screened out six variables, including positive end-expiratory pressure (PEEP), MP, dynamic lung compliance (Cdyn), inspired oxygen concentration (FiO₂), length of ICU stay and IMV duration, with coefficients of 0.144, 0.047, -0.032, 0.027, 0.090 and 0.098, respectively. Logistic regression analysis showed that the six variables were all independent risk factors for predicting weaning failure risk [odds ratio (OR) and 95% confidence interval (95%CI) were 1.155 (1.111-1.200), 1.048 (1.031-1.066), 0.968 (0.963-0.974), 1.028 (1.017-1.038), 1.095 (1.076-1.113), and 1.103 (1.070-1.137), all P < 0.01]. The MP-oriented nomogram prediction model of weaning failure in mechanically ventilated patients showed accurate discrimination both in the model group and external validation group, with area under the ROC curve (AUC) and 95%CI of 0.832 (0.819-0.845) and 0.879 (0.833-0.925), respectively. Furthermore, its predictive accuracy was significantly higher than that of individual indicators such as MP, Cdyn, and PEEP. Calibration curves showed good correlation between predicted and observed outcomes. DCA indicated that the nomogram model had high net benefits, and was clinically beneficial. CONCLUSIONS The MP-oriented nomogram prediction model of weaning failure accurately predicts the risk of weaning failure in mechanical ventilation patients and provides valuable information for clinicians making decisions on weaning.
Humans ; Respiration, Artificial/methods* ; Ventilator Weaning/methods* ; Nomograms ; Lung ; Risk Factors

Humans ; Retroperitoneal Neoplasms ; Liposarcoma ; Calcium-Binding Proteins ; Mixed Function Oxygenases ; Membrane Proteins ; Muscle Proteins

Background: Recent studies have reported that costoclavicular blocks (CCBs) can consistently block almost all branches of the brachial plexus while sparing the phrenic nerve and provide effective analgesia after shoulder surgery. We aimed to compare the efficacy of the CCB with that of the interscalene block (ISB) as the sole blocking technique for shoulder surgery. Methods: A total of 212 patients undergoing elective arthroscopic shoulder surgery were randomized to receive an ISB or CCB based on a non-inferiority design. All patients received titration sedation with propofol under monitored anesthesia during surgery. The primary outcomes were the proportion of patients with complete motor blockade of the suprascapular nerve (SSN) and incidence of hemidiaphragmatic paralysis (HDP). The secondary outcomes included block-related variables, complications, and postoperative pain scores. Results: The proportion of patients with complete motor blockade of the SSN at 20 min between the CCB and ISB groups (53% vs. 66%) exceeded the predefined non-inferiority margin of −5%, but was comparable at 30 min (87% vs. 91%). The CCB resulted in a significantly lower incidence of HDP (7.55% vs. 92.45%), Horner’s syndrome (0% vs. 18.87%), and dyspnea (0% vs. 10.38%) than the ISB. None of the patients experienced failed blocks or required conversion to general anesthesia. Pain scores were comparable between the groups. Conclusions Ultrasound-guided CCBs may be comparable to ISBs, with fewer unfavorable complications in patients with impaired lung function undergoing arthroscopic shoulder surgery.

In recent years, it has been common for heart disease patients to undergo urological surgery.The requirements for specialized doctors to accurately assess the risk of perioperative heart disease thrombosis are also increasing. In order to conduct multi-disciplinary disease analysis and discussion in a more standardized profile and promote clinical work progress in a safer manner, this article provides a systematic review and summary of the basic characteristics of antithrombotic drugs, the bleeding risks of urological surgery, the risk identification standards for arteriovenous thrombosis, as well as the withdrawal conditions, bridging selection, and restart treatment of perioperative antithrombotic drugs, based on the constantly updated clinical researches and guideline consensuses in recent years.

Objective To develop plantar force model of patellofemoral pain (PFP), so as to provide theoretical references for the assessment of PFP rehabilitation. Methods The case-control study was conducted, and a total of 126 patients with PFP and 126 healthy controls matched by gender and age were enrolled in the study. The participants were tested for plantar force and pressure during level walking, and twelve plantar regions were divided and recorded. Whether the participants suffered PFP was analyzed as dependent variable, meanwhile the peak force and peak pressure in 12 plantar regions of participants at selected speed during level walking were analyzed as independent variables. Conditional logistic regression (CLR) equations of peak force and peak pressure with PFP were established, respectively. The receiver-operating characteristic (ROC) curve of the corresponding equations was derived, and the area under ROC curve was calculated to analyzed the validity of different equations on PFP assessment. Results The CLC equation of peak force in 12 plantar regions of the participants with FFP was constructed, and only peak force of lateral heel was in the equation. The CLC equation of peak pressure in each plantar region included medial heel, midfoot, 1st and 2nd metatarsals. Meanwhile, the area under ROC curve of the pressure equation was larger than that of the force equation. Conclusions Peak force and pressure at different plantar regions can be used to assess PFP during level walking, and peak pressure is more effective for assessment.

Objective:To analyze the operative outcomes and postoperative pathological features of retroperitoneal leiomyosarcoma(RPLMS) undergoing surgeries.Methods:Medical records of RPLMS patients admitted to Peking University International Hospital from Jan 2015 through Dec 2020 were retrospectively reviewed.Results:Ninety-seven patients undergoing resectional surgeries were included in the study. Of whom, 49 cases were primary RPLMS. Others were recurrent sarcomas or sarcomas with incomplete resection in the first surgical intentions. The most frequent symptoms were abdominal pain and distention (30 cases) as well as lower back pain (23 cases). All patients underwent resectional surgeries with a R 0/R 1 rate of 84.5%. Sixty-four cases received extended surgeries with combined organs resection. External iliac artery resection with reconstruction were performed on 2 cases. And 19 patients underwent partial IVC resection in combination of sarcoma resection. The general postoperative morbidity was 26.8%, including 4 intestinal fistulas, 1 pancreatic fistula, 1 vesicovaginal fistula, 1 urinary fistula, 1 biliary fistula, 2 abdominal major bleeding, 7 IVC thrombosis, 3 gastroplegiaetc. One patient deceased within post-operative 30 d due to massive bleeding.Pathology found that spindle and pleomorphic cell types were most common subtypes of RPLMS. Conclusions:Surgery remains the mainstay in the treatment of RPLMS which often presents with atypical symptoms. Extended surgeries combining with multiple organ and major vascular resections could be only suggested in experienced sarcoma centers due to high risk of severe postoperative complications.

目的：探讨miRNA-490-3p调控Smad2/TGF-β对结直肠癌奥沙利铂化疗敏感性的影响。方法：选取100例结直肠癌（colorectal cancer，CRC）根治性手术后奥沙利铂（oxaliplatin，OXA）同种联合化疗患者作为研究对象，根据化疗情况分为耐药组（n=40）和非耐药组（n=60），用qPCR检测两组外周血miRNA-490-3p水平；选取人CRC细胞株SW480和CRC奥沙利铂（OXA）耐药型细胞株OXA-SW480进行研究，先用qPCR检测两种细胞株中miRNA-490-3p表达水平；后将miRNA-490-3p过表达载体转染OXA-SW480（过表达组），并设立空载体组（空载体转染OXA-SW480）和空白对照组（OXA-SW480未经任何处理）。用CCK-8检测各组细胞增殖能力，同时用不同浓度OXA处理各组细胞，计算其半数抑制浓度（IC50）；用Annexin-V-FITC/PI染色流式细胞术检测各组细胞凋亡率；用WB检测各组Smad2和TGF-β蛋白表达水平。结果：在CRC患者中，耐药组外周血miR-490-3p水平显著低于非耐药组，在CRC细胞株中，OXA-SW480耐药株细胞miR-490-3p水平显著低于正常株SW480细胞（P<0.05）。与空载体组和空白对照组相比，过表达组miR-490-3p水平显著降低（均P<0.05），增殖抑制率显著升高（均P<0.05），细胞凋亡率显著升高（均P<0.01），Smad2蛋白水平显著降低（均P<0.05），TGF-β蛋白水平显著升高（均P<0.05）。经OXA处理后，过表达组的IC50显著低于空载体组和空白对照组（均P<0.05）。经Pearson相关法分析，miR-490-3p与Smad2的表达呈负相关（r=–0.943，P<0.01），miR-490-3p与TGF-β的表达呈正相关（r=0.961，P<0.01）。结论：过表达miRNA-490-3p可增加CRC SW480细胞的OXA敏感性，此作用Smad2/TGF-β信号通路有关。

Objective:To summarize the experience of surgical treatment of pelvic retroperitoneal neoplasms.Methods:A total of 107 patients with pelvic retroperitoneal neoplasms underwent surgical treatment from Apr 2015 to Sep 2020. According to the neoplasm location, size, and the relationship with the surrounding tissues, individualize the surgical plan, analyze the patient's basic condition, bleeding volume, tumor size, whether it is the first operation,or combined organ resection, etc.to find out the relevant factors affecting the surgical complications.Results:The surgical route included anterior approach in 67 cases , sacrococcygeal approach in 21 cases, combined abdominal-sacral approach in 13 cases, and laparoscopy in 5 cases. Twenty-nine patients underwent combined organ resection, postoperative complications occurred in 27 patients including colorectal anastomotic leakage in 6 cases, urinary fistula in 6 cases, delayed pelvic floor healing in 6 cases, rectovaginal fistula in 3 cases, and postoperative bleeding in 2 cases. The statistical analysis show whether or not first operation is related to the occurrence of complications ( χ2=4.79, P<0.05) Conclusion:Pelvic retroperitoneal neoplasms need to be fully prepared before surgery and individualized design. Intraoperative combined bleeding control measures and combined organ resection can effectively increase the resection rate and ensure the safety of surgery.

Objective:To investigate the multiple origin of retroperitoneal liposarcoma and its postoperative prognosis.Methods:A total of 49 retroperitoneal liposarcoma patients underwent total (ipsilateral) retroperitoneal lipectomy in our center from May 2017 to December 2019 were recruited. Clinical data and the follow-up information were reviewed and the origin and prognosis were analyzed.Results:A total of 15 patients were pathologically diagnosed as multiple primary cancer (MPC), the incidence rate of retroperitoneal liposarcoma with MPC was 30.6% (15/49), while other 34 cases was non-MPC. The postoperative recurrence rates of patients with high differentiation and de-differentiation retroperitoneal liposarcoma were 31.8% and 44.4%, without significant difference ( P>0.05). The postoperative recurrence rates of MPC and non-MPC were 40.0% and 38.2%, without significant difference ( P>0.05). Five cases died within the follow-up. Conclusion:Retroperitoneal liposarcoma might origin form MPC, and total (ipsilateral) retroperitoneal lipectomy is recommended to reduce the recurrence rate.