[Clinical characteristics and prognosis of primary aldosteronism associated with subclinical Cushing syndrome].

Objective: To analyze the clinical characteristics and prognosis of patients with primary aldosteronism (PA) associated with subclinical Cushing syndrome (SCS). Methods: This retrospective cohort study was conducted at the First Affiliated Hospital of Chongqing Medical University in China. Patients with PA were included between January 2014 and December 2022. According to the results of 1-mg overnight dexamethasone suppression test, the patients were divided into the PA group and PA associated with SCS (PA/SCS) group. The demographic information, hormone levels, and follow-up results were analyzed. Independent sample t-test, chi-square test and Mann-Whitney U test were used for data comparison. Results: A total of 489 PA patients were enrolled in this study, of which 109 had PA/SCS (22.3%). Patients with SCS were on average older (54.4±10.7 vs. 47.4±11.0, P<0.001); had a larger proportion of women (69.7%, 76/109 vs. 57.4%, 218/380; P=0.020); and a longer duration of hypertension [96 (36, 180) vs. 60 (12, 120) months, P=0.001] than patients without SCS. There were 215 and 51 patients in the PA group and PA/SCS group, who completed adrenalectomy and follow-up, respectively. The remission rate of autonomous cortisol secretion in the PA/SCS group was 85.3% (29/34). There was no significant difference in the remission rate of autonomous aldosterone secretion among patients between the PA/SCS and PA group (94.1%, 48/51 vs. 94.4%, 203/215; P=1.000), while the clinical remission rate in the PA/SCS group was lower than that in the PA group (39.2%, 20/51 vs. 61.9%, 133/215; P=0.003). Conclusions: SCS is common in PA patients (22.3%), and the clinical remission rate is low. Screening using the 1-mg overnight dexamethasone suppression test is recommended for all patients with PA.

[Study of appropriate cut-off for diagnosis of primary aldosteronism by seated saline suppression test based on liquid chromatography with tandem mass spectrometry].

Objective: To investigate the appropriate cut-off for diagnosis of primary aldosteronism (PA) by seated saline suppression test (SSST) based on liquid chromatography with tandem mass spectrometry (LC-MS/MS). Methods: In this cross-sectional study, patients who underwent SSST for suspected PA in the First Affiliated Hospital of Chongqing Medical University from January 2018 to March 2022 were evaluated. Briefly, 300 patients with PA and 119 with essential hypertension (EH) were included. Plasma aldosterone concentration (PAC) after SSST was determined by LC-MS/MS. Primary aldosteronism confirmatory testing (PACT) score was used as the reference standard for diagnosis of PA, and receiver operating characteristic (ROC) curve was used to explore the cut-off value. Results: The average age of the PA group was (50.8±10.5) years, and males accounted for 53.00% (n=159); the average age of the EH group was (49.4±11.2) years, and males accounted for 26.89% (n=32). The area under the ROC curve of PAC post-SSST was 0.819 (95%CI 0.775-0.862). When 40 pg/ml (110.8 pmol/L) was selected as the appropriate cut-off for diagnosis of PA, the sensitivity was 83.67% (95%CI 78.88%-87.56%) and specificity was 60.50% (95%CI 51.10%-69.21%). Thus, 95.09% (155/163) of patients with unilateral PA could be identified. Conclusion: PAC after SSST determined by LC-MS/MS has high efficacy for diagnosis of PA, and 40 pg/ml is recommended as the appropriate cut-off value.

[Distribution characteristics of plasma renin concentration in patients with aldosterone-producing adenoma].

Objective: To analyze the distribution characteristics of plasma renin concentration (PRC) in patients with aldosterone-producing adenoma (APA) and its impact on diagnosis. Methods: In this retrospective case series, clinical data from 200 patients with APA (80 men and 120 women; mean age 45.6 years) in the First Affiliated Hospital of Chongqing Medical University from November 2013 to January 2022 were evaluated. PRC was determined by automated chemiluminescence immunoassay. The distribution characteristics of PRC were analyzed, and 8.2 mU/L was used as the low renin cutoff to evaluate whether renin was suppressed. Results: The median PRC was 1.6 mU/L (range, 0.4-41.5 mU/L). There were 116 patients with APA with PRC of ≤2 mU/L, 41 patients with 28.2 mU/L) in 8.0% (16/200) of the patients with APA. And PRC was not suppressed in 2.5% (5/200) of the patients with APA, resulting in a primary aldosteronism negative screening outcome. Conclusions: Although most patients with APA have low PRC, there are a small number (8%) of patients whose PRC has not been fully suppressed, which can lead to missed diagnoses during primary aldosteronism screening. While primary aldosteronism is highly suspected, further investigations are required to determine the diagnosis, even if PRC is not fully suppressed at screening.

[Differential diagnosis and surgical management in chondrosarcoma of the jugular foramen].

Objective: To explore the diagnosis, surgical management and outcome of jugular foramen chondrosarcoma (CSA). Methods: Fifteen patients with jugular foramen CSA hospitalized in the Department of Otorhinolaryngology Head and Neck Surgery of Chinese PLA General Hospital from December 2002 to February 2020 were retrospectively collected,of whom 2 were male and 13 were female, aging from 22 to 61 years old. The clinical symptoms and signs, imaging features, differential diagnosis, surgical approaches, function of facial nerve and cranial nerves IX to XII, and surgical outcomes were analyzed. Results: Patients with jugular foramen CSA mainly presented with facial paralysis, hearing loss, hoarseness, cough, tinnitus and local mass. Computed tomography (CT) and magnetic resonance (MR) could provide important information for diagnosis. CT showed irregular destruction on bone margin of the jugular foramen. MR demonstrated iso or hypointense on T1WI, hyperintense on T2WI and heterogeneous contrast-enhancement. Surgical approaches were chosen upon the sizes and scopes of the tumors. Inferior temporal fossa A approach was adopted in 12 cases, inferior temporal fossa B approach in 2 cases and mastoid combined parotid approach in 1 case. Five patients with facial nerve involved received great auricular nerve graft. The House Brackmann (H-B) grading scale was used to evaluate the facial nerve function. Preoperative facial nerve function ranked grade Ⅴ in 4 cases and grade Ⅵ in 1 case. Postoperative facial nerve function improved to grade Ⅲ in 2 cases and grade Ⅵ in 3 cases. Five patients presented with cranial nerves Ⅸ and Ⅹ palsies. Hoarseness and cough of 2 cases improved after operation, while the other 3 cases did not. All the patients were diagnosed CSA by histopathology and immunohistochemistry, with immunohistochemical staining showing vimentin and S-100 positive, but cytokeratin negative in tumor cells. All patients survived during 28 to 234 months' follow-up. Two patients suffered from tumor recurrence 7 years after surgery and received revision surgery. No complications such as cerebrospinal fluid leakage and intracranial infection occurred after operation. Conclusions: Jugular foramen CSA lacks characteristic symptoms or signs. Imaging is helpful to differential diagnosis. Surgery is the primary treatment of jugular foramen CSA. Patients with facial paralysis should receive surgery in time as to restore the facial nerve. Long-term follow-up is necessary after surgery in case of recurrence.

[Establishment and validation of a nomogram-based predictive model for idiopathic aldosteronism].

Objective: To establish and validate a nomogram-based predictive model for idiopathic hyperaldosteronism (IHA). Methods: This cross-sectional study was conducted with the collected clinical and biochemical data of patients with primary aldosteronism (PA) including 249 patients with unilateral primary aldosteronism (UPA) and 107 patients with IHA, who were treated at the Department of Endocrinology of the First Affiliated Hospital of Chongqing Medical University from November 2013 to November 2022. Plasma aldosterone concentration (PAC) and plasma renin concentration (PRC) were measured by chemiluminescence. Stepwise regression analysis was applied to select the key predictors of IHA, and a nomogram-based scoring model was developed. The model was validated in another external independent cohort of patients with PA including 62 patients with UPA and 43 patients with IHA, who were diagnosed at the Department of Endocrinology, First Affiliated Hospital of Zhengzhou University. An independent-sample t test, Mann-Whitney U test, and χ2 test were used for statistical analysis. Results: In the training cohort, in comparison with the UPA group, the IHA group showed a higher serum potassium level [M(Q1, Q3), 3.4 (3.1, 3.8) mmol/L vs. 2.7 (2.1, 3.1) mmol/L] and higher PRC [4.0 (2.1, 8.2) mU/L vs. 1.5 (0.6, 3.4) mU/L] and a lower PAC post-saline infusion test (SIT) [305 (222, 416) pmol/L vs. 720 (443, 1 136) pmol/L] and a lower rate of unilateral adrenal nodules [33.6% (36/107) vs. 81.1% (202/249)]; the intergroup differences in these measurements were statistically significant (all P<0.001). Serum potassium level, PRC, PAC post-SIT, and the rate of unilateral adrenal nodules showed similar performance in the IHA group in the validation cohort. After stepwise regression analysis for all significant variables in the training cohort, a scoring model based on a nomogram was constructed, and the predictive parameters included the rate of unilateral adrenal nodules, serum potassium concentration, PAC post-SIT, and PRC in the standing position. When the total score was ≥14, the model showed a sensitivity of 0.65 and specificity of 0.90 in the training cohort and a sensitivity of 0.56 and specificity of 1.00 in the validation cohort. Conclusion: The nomogram was used to successfully develop a model for prediction of IHA that could facilitate selection of patients with IHA who required medication directly.

A sustained high-temperature fusion plasma regime facilitated by fast ions.

Nuclear fusion is one of the most attractive alternatives to carbon-dependent energy sources1. Harnessing energy from nuclear fusion in a large reactor scale, however, still presents many scientific challenges despite the many years of research and steady advances in magnetic confinement approaches. State-of-the-art magnetic fusion devices cannot yet achieve a sustainable fusion performance, which requires a high temperature above 100 million kelvin and sufficient control of instabilities to ensure steady-state operation on the order of tens of seconds2,3. Here we report experiments at the Korea Superconducting Tokamak Advanced Research4 device producing a plasma fusion regime that satisfies most of the above requirements: thanks to abundant fast ions stabilizing the core plasma turbulence, we generate plasmas at a temperature of 100 million kelvin lasting up to 20 seconds without plasma edge instabilities or impurity accumulation. A low plasma density combined with a moderate input power for operation is key to establishing this regime by preserving a high fraction of fast ions. This regime is rarely subject to disruption and can be sustained reliably even without a sophisticated control, and thus represents a promising path towards commercial fusion reactors.

[Paratesticular liposarcoma: the clinicopathological features of nineteen cases].

Objective: To investigate the clinicopathological features and differential diagnoses of paratesticular liposarcoma. Methods: The cases were collected from 2012-2020, from the archives of the Department of Pathology, Peking University Third Hospital, with diagnosis confirmed by histology, immunostaining and FISH tests. Results: Totally 19 patients were enrolled (including 11 in-hospital patients and 8 consultant cases). The patients aged 37-84 years (mean 57 years). The preoperative clinical diagnoses were spermatic cord/inguinal masses (nine patients), scrotal masses (seven patients), and inguinal hernia (three patients). Six lesions recurred after local resection, including one case extending from pelvic liposarcoma. Histologically, there were 10 cases of well-differentiated liposarcoma (WDLPS) and nine cases of dedifferentiated liposarcoma (DDLPS). WDLPSs mostly showed the combined features of lipoma-like, inflammatory and sclerosing subtypes (six patients); the other four WDLPSs had pure lipoma-like subtype features. DDLPSs were low-grade (three patients) or high-grade (six patients), with the morphology resembling myxofibrosarcoma, inflammatory myofibroblastoma, spindle cell sarcoma, pleomorphic undifferentiated sarcoma and pleomorphic liposarcoma. Intense inflammatory cells infiltration was commonly observed in five WDLPSs and two DDLPSs. Ossification was observed in three tumors. Immunohistochemically, the tumors were positive for MDM2 (8/10) and CDK4 (10/10), which were expressed in lipo-differentiating cells, spindle cells in WDLPS, and in dediffferentiated components. S-100 was only expressed by lipocytes (10/10). CD34 expression was positive and diffuse in the stromal cells of WDLPSs and focal or diffuse in dedifferentiated areas (10/10). FISH tests with an MDM2 gene probe were positive (12/12). Conclusions: Paratesticular liposarcoma may be overlooked by both clinicians and pathologists. WDLPS and DDLPS predominate, showing various histologic divergences. The presence of amplification of the 12q14-q15 region (containing the MDM2 and CDK4 genes) is helpful for making the correct diagnosis.

[Re-evaluation of the diagnostic value and optimal cutoff point of captopril challenge test in diagnosis of primary aldosteronism].

Objective: The aim of the present study was to re-evaluate the diagnostic value and optimal cutoff point of captopril challenge test (CCT) in diagnosis of primary aldosteronism (PA). Methods: This is a retrospective study. All patients with a high risk for PA underwent screening test, and then proceeded to CCT and fludrocortisone suppression test (FST) on different days. The FST was used as a reference standard for PA. The plasma renin concentration (PRC) and plasma aldosterone concentration (PAC) were measured with an automated chemiluminescence immunoassay. Random number method was performed in the patients with unilateral primary aldosteronism (UPA), in order to make the proportion of the analyzed UPA in PA was 35%. Receiver operating characteristic (ROC) analyses were performed to compare diagnostic accuracy. Results: A total of 543 patients with 400 PA patients and 143 essential hypertension (EH) patients were enrolled. The diagnostic value of post-CCT PAC was significantly higher than that of the post-CCT plasma aldosterone-renin ratio (ARR), and that of the PAC suppression percentage, respectively. The area under the ROC curve (AUCROC) was 0.86 (0.83, 0.89) for PAC, 0.78 (0.74, 0.82) for ARR, and 0.62 (0.56, 0.67) for the PAC suppression percentage (all P<0.01), respectively. The optimal cutoff point of post-CCT PAC for PA was 110 ng/L, in which the sensitivity and specificity were 73.25% and 79.02%, respectively. The diagnostic efficiency of post-CCT PAC was not improved either in combination with PAC suppression percentage or in combination with post-CCT ARR. Conclusions: CCT is a useful test for the confirmation of PA. PAC level of 110 ng/L at 2 h after 50 mg of captopril is recommended as an optimal cutoff point for the diagnosis of PA.

A randomised controlled trial of 7.5-mm and 7.0-mm tracheal tubes vs. 6.5-mm and 6.0-mm tracheal tubes for men and women during laparoscopic surgery.

Sore throat after tracheal intubation impairs postoperative recovery. We randomly allocated 172 ASA physical status 1-2 participants, scheduled for laparoscopic lower abdominal surgery, to tracheal intubation with larger tubes (n = 88) or smaller tubes (n = 84), with internal diameters 7.5-mm vs. 6.5-mm for men and 7.0-mm vs. 6.0-mm for women. Primary outcome was the rates of no, mild, moderate or severe sore throat 1 h after surgery, which were 60, 10, 17 and 1 with larger tracheal tubes and 79, 5, 0 and 0 with smaller tubes, p < 0.001. The equivalent rates 24 h after surgery were 64, 16, 8 and 0 vs. 74, 6, 3 and 1, p = 0.037. Intra-operative ventilatory variables were unaffected by tube diameter, including peak inspiratory pressure, plateau pressure and end-tidal carbon dioxide partial pressure. In summary, smaller tracheal tubes benefitted patients having laparoscopic operations.

[The molecular mechanism of oxaliplatin-induced peripheral neuropathic pain].

Objective: To investigate the molecular mechanism of oxaliplatin-induced chemotherapy-induced peripheral neuropathic pain (CIPNP). Methods: A total of 16 male Sprague-Dawley rats of specific pathogen-free grade were randomly divided into two groups: oxaliplatin experimental group (2.4 mg/kg oxaliplatin dissolved in 5.0% glucose solution, n=8) and control group (equal volume 5% glucose solution, n=8). The rat model of CIPNP was established by continuous administration with oxaliplatin. In addition, mechanical allodynia, thermal hyperalgesia and cold hyperalgesia were measured and compared between the two groups. To explore the molecular mechanism of oxaliplatin-induced CIPNP, the gene expression of dorsal root ganglia (DRG) from the rat model of CIPNP was analyzed using RNA sequencing (RNA-Seq). Results: Mechanical and thermal hypersensitivity was exhibited on day 7 and a stronger hypersensitivity was observed on day 14. A total of 20 152 genes were quantified by RNA-Seq, and 379 differentially expressed genes (DEGs) were obtained with absolute fold change cut-offs ≥ 2 and P value<0.05. There were 7 genes (Npy, Car3, Cdkn1a, Nts, Prc1, Ms4a7 and Ecel1) that were involved in peripheral nerve injury-related neuropathic pain. Gene ontology (GO) functional enrichment analyses indicated that the DEGs induced by oxaliplatin were involved in oxygen transport, cell division, intermediate, centromere, oxygen transporter activity, oxygen binding. Moreover, the result of Kyoto Encyclopedia of genes and genomes (KEGG) analyses highlighted that the DEGs induced by oxaliplatin were involved in malaria, African trypanosomiasis, primary immunodeficiency, peroxisome proliferator activated receptor (PPAR) signaling pathway. Conclusion: Oxaliplatin induces CIPNP via pain-related genes and signaling pathways.

Development of an Improved Rapidly Exploring Random Trees Algorithm for Static Obstacle Avoidance in Autonomous Vehicles.

Safe path planning for obstacle avoidance in autonomous vehicles has been developed. Based on the Rapidly Exploring Random Trees (RRT) algorithm, an improved algorithm integrating path pruning, smoothing, and optimization with geometric collision detection is shown to improve planning efficiency. Path pruning, a prerequisite to path smoothing, is performed to remove the redundant points generated by the random trees for a new path, without colliding with the obstacles. Path smoothing is performed to modify the path so that it becomes continuously differentiable with curvature implementable by the vehicle. Optimization is performed to select a "near"-optimal path of the shortest distance among the feasible paths for motion efficiency. In the experimental verification, both a pure pursuit steering controller and a proportional-integral speed controller are applied to keep an autonomous vehicle tracking the planned path predicted by the improved RRT algorithm. It is shown that the vehicle can successfully track the path efficiently and reach the destination safely, with an average tracking control deviation of 5.2% of the vehicle width. The path planning is also applied to lane changes, and the average deviation from the lane during and after lane changes remains within 8.3% of the vehicle width.