Objective To explore the differences of adrenal imaging indicators of patients with subclinical Cushing syndrome (SCS) and different cortisol levels, and analyze the related influencing factors. Methods Retrospectively analyze the clinical data of 65 patients with SCS admitted in the Department of Endocrinology of the First Medical Center of Chinese PLA General Hospital from January 2010 to January 2020. Subjects were undergone 1 mg dexamethasone suppression test (DST) at midnight, then with the blood cortisol level of 138 nmol/L at 8:00 am as a cut-off (1 mg DST-F_8:00), divided into low-level group(n=36) and high-level group (n=29). The clinical characteristics, biochemical indicators, adrenocorticotropic hormone-cortisol(ACTH-F), tumor size, CT value and contralateral adrenal gland image of the two groups were compared. The relationship of contralateral adrenal width to the related factors between the both groups were analyzed by logistic regression, and then multivariate linear regression analysis was performed to analyze the relationship of the contralateral adrenal length, width and height to the different metabolic indicators. Results No statistically significant difference in the course of disease, body mass index (BMI),blood pressure, blood glucose, blood lipid, bone density, and related metabolic abnormalities existed between the two groups. While the patients were significantly younger (P<0.001), the SCS onset time was much earlier (P<0.001), and the proportion of female patients was higher (P=0.014) in high-level group than those in low-level group. In addition, the cortisol level at midnight (F_00.00)and 1 mg DST-F_8:00 were obviously higher in high-level group than those in low-level group (P<0.001). No significant difference existed between the two groups in tumor size, CT value, contralateral adrenal gland length, height and volume, but the width was thinner in high-level group than those in low-level group (P=0.07). The level of 1 mg DST-F_8:00 in SCS patients was negatively correlated with the width of contralateral adrenal gland (β=–1.79, 95%CI –3.05-–0.52, P=0.007). Using sex, age, age of onset, course of disease, BMI, ACTH level, and tumor diameter as adjustment variables, logistic regression was singularly performed to analyze the relationship between 1 mg DST-F_8:00 and the width of contralateral adrenal gland in SCS patients, then the results were still consistent. Multivariate linear regression showed that the width of contralateral adrenal gland was negatively correlated with diastolic blood pressure (β=–2.484, 95%CI –3.883-–1.085, P=0.002), while the contralateral adrenal length and height showed no obvious correlations with the metabolic index. Conclusion SCS patients with higher level of 1 mg DST-F_8:00 had thinner contralateral adrenal gland width and with higher diastolic blood pressure.

Objective To summarize and analyze the composition features of large adrenal mass for guiding the clinical treatment. Methods The clinical data of 493 cases of large adrenal mass (≥4 cm), admitted in the Chinese PLA General Hospital from January 2016 to December 2020, were collected and retrospectively analyzed, including gender, age, reason for first visit,operation or not, postoperative pathological diagnosis and imaging data. According to the endocrine function evaluation results,all the cases were divided into functional adrenal masses (n=264) and non-functional masses (n=229), and then, according to the tumor nature, they were divided into benign masses (n=348) and malignant masses (n=145), the spectrum of large adrenal masses were analyzed. Results (1) The mean age was (47.7±14.3) years old. Adrenal incidentalomas is the mainly reasons for first visit (n=289, 58.6%). (2) Of the 493 patients reviewed, the proportion of functional adrenal masses (n=264) was higher than non-functional masses (n=229) [53.6% vs. 46.4%]. Pheochromocytomas occupied the highest proportion among functional masses(65.5%), Myelolipoma occupied the highest proportion among non-functional masses (22.3%). There was no significant difference in age, gender, lesion location and tumor diameter between functional masses group and non-functional masses group. (3) Of the 493 patients, the proportion of benign adrenal masses was higher than malignant masses [70.6% (348/493) vs. 29.4% (145/493)].Compared with benign masses, the tumor diameter in malignant masses group was significantly larger [(73.85±29.84) mm vs.(67.12±26.69) mm, P<0.05]. Pheochromocytoma occupied the first proportion in both benign (32.2%) and malignant masses(42.1%). There was no significant difference in age, gender, and lesion location between the two groups. Conclusions Among the patients with large adrenal mass (≥4 cm), pheochromocytomas occupied the highest proportion and adrenal incidentalomas was the mainly reasons for visiting doctors. Functional adrenal masses were more than non-functional adrenal masses, and benign masses were more than malignant adrenal masses. Malignant masses showed the larger tumor diameter.

Objective By comparison of the urinary free cortisol (UFC) levels in post- to prior-dexamethasone suppression test (post UFC/pre UFC) with primary pigmented nodular adrenocortical disease (PPNAD), primary bilateral macronodular adrenal hyperplasia (PBMAH) and adrenocortical adenoma (ADA), to explore the optimal differential diagnostic cut-off point of PPNAD from PBMAH and ADA. Methods The clinical data were collected and retrospectively analyzed of in patients admitted from January 2008 to December 2020 with finally diagnosed as PPNAD (n=7), PBMAH (n=31) and ADA (n=130) in the First Medical Center of Chinese PLA General Hospital. Based on the receiver operating characteristic (ROC) curve, the value of post UFC/pre UFC in low-dose dexamethasone suppression test (LDDST) and high-dose dexamethasone suppression test (HDDST)was used as the detection variable, and the diagnosis of PPNAD was used as the status variable to search the best cut-off point for the differential diagnosis of PPNAD. Results The serum cortisol (F) levels of all the 3 groups of patients (PPNAD, PBMAH and ADA) increased significantly in the baseline, LDDST and HDDST, and no statistical difference existed among them (P>0.05). The adrenocorticotropic hormone (ACTH) levels in all the 3 groups of patients were inhibited, and ACTH levels in PBMAH group were the highest at the baseline and after HDDST, and the ACTH levels of ADA group were the lowest among the three groups (P<0.05).The baseline 24 h UFC levels elevated obviously with no statistical difference (P>0.05) among the three groups. For patients in PPNAD group, the LDDST post UFC/pre UFC [1.88(1.39, 2.59)] was obviously higher than that in PBMAH group [1.13(0.82,1.37), P=0.001] and ADA group [1.11(0.70, 1.49), P=0.003]; and the HDDST post UFC/pre UFC in PPNAD group [2.31(1.23,3.08)] was still higher than that in PBMAH group [1.22(0.94, 1.63), P=0.004] and ADA group [1.39(1.08, 1.53), P=0.008].Compared with PBMAH group and ADA group, the diagnostic cut-off point for PPNAD group after LDDST post UFC/pre UFC was 1.385, with 85.7% sensitivity and 71.5% specificity; and after HDDST post UFC/pre UFC was 2.290, with 57.1% sensitivity and 95.0% specificity. Conclusion The cut-off points of post UFC/pre UFC in DST had a clear advantage in distinguishing PPNAD from PBMAH and ADA. The diagnosis of PPNAD may be considered once the value of post UFC/pre UFC after LDDST is greater than 1.385, or after HDDST is above 2.290.

Objective To investigate the effects of treadmill exercise on the motor function and mammalian target of rapamycin (mTOR) signal pathway in motor cortex of adult mice with spinal cord injury. Methods Thirty C57BL/6J mice were randomly divided into sham group, model group and treadmill exercise group (10 each). All mice received pre-training for 3 days, and those in model group and treadmill exercise group were crushed with C₅ after pre-training in dorsal cortico-spinal tract,left cortico-spinal tract and rubro-spinal tract. The lamina was removed without damaging the spinal cord in sham group. Mice in treadmill exercise group began to run on the platform 1 week after injury, 5 days every week for 4 weeks. The motor function recovery was assessed with Basso Mouse Scale (BMS), horizontal ladder and cylinder rearing tests. The expression of insulin-like growth factor 1 (IGF-1), brain-derived neurotrophic factor (BDNF) and the phosphorylated level of tyrosine kinase receptor B (TrkB), insulin-like growth factor 1 receptor (IGF-1R), protein kinase B (Akt), and ribosomal S6 protein (S6) in motor cortex of mice were detected by Western blotting. The activation of cortical mTOR pathway was evaluated with immunofluorescence staining to detect the phosphorylated level of S6 in motor neurons. Results After injury, the BMS score of mice in model group and treadmill exercise group decreased briefly (P<0.0001), and recovered back to baseline level within 7 days. Compared with sham group, the error rate of left forelimb and left hindlimb increased (P<0.001) both in model group and treadmill exercise group 3 days, 1 week, 3 weeks and 5 weeks after injury. Compared with model group, the error rate of both left forelimb and left hindlimb decreased (P<0.001) in treadmill exercise group 3 and 5 weeks after injury. Compared with sham group, the utilization rate of left forelimb decreased (P<0.0001) both in model group and treadmill exercise group 3 days and 1 week after injury;and 3 and 5 weeks after injury, the utilization rate of left forelimb was still lower in model group than in sham group (P<0.001),while no statistical significant difference between the treadmill exercise group and sham group (P>0.05). Western blotting and immunofluorescence staining results showed that compared with sham group, the relative expression levels of BDNF and IGF-1 and the phosphorylation levels of TrkB, IGF-1R, Akt and S6 in the motor cortex of model group and treadmill exercise group decreased obviously, and the fluorescence intensity of p-S6 staining in neurons significantly decreased (P<0.01). Compared with model group, the relative expression levels of IGF-1, BDNF and the phosphorylation levels of TrkB, IGF-1R, Akt and S6 in the motor cortex of mice in treadmill exercise group increased significantly, and the fluorescence intensity of p-S6 staining in neurons significantly increased in treadmill exercise group (P<0.01). Conclusion The treadmill exercise is beneficial to the recovery of motor function in mice with spinal cord injury, which may be related to exercise-induced the expressions of BDNF, IGF-1 and activation of mTOR in motor cortex.

Objective To identify the differentially expressed microRNA (miRNA, miR) in cervical squamous cell carcinoma (SCC) and explore the mechanism of critical miRNA on the occurrence and development of cervical cancer. Methods To identify differentially expressed miRNA, we employed bioinformatics methods to filter out miRNA under the conditions of |fold change(FC)|>2.5 and P<0.01. The RNA expressions of miR-205 and interleukin-32 (IL-32) were detected by in situ hybridization and qRT-PCR, respectively. We evaluated cell proliferation, migration, and invasion through CCK-8 and Transwell model. The protein level of matrix metalloproteinase-3 (MMP-2) and MMP-9 were quantified by Western blotting. Results Through bioinformatics analysis, we obtained 106 differentially expressed miRNA in cervical cancer, with 70 up-regulated and 36 down-regulated miRNAs. miR-205 was the most differentially expressed miRNA. We validated the overexpression of miR-205 in cervical squamous cell carcinoma by in situ hybridization and qRT-PCR (P<0.05). Overexpression of miR-205 could significantly promote the proliferation, migration, and invasion of cervical cancer cells (P<0.05). The overexpression or decreased expression of miR-205 can increase or inhibit the expression of IL-32 in cervical cancer cell lines HeLa and SiHa, and miR-205 can directly interact with the IL-32 promoter to increase the expression of target genes (P<0.05); the decreased expression of miR-205 and IL-32 inhibited the invasion of cells (P<0.05); moreover, the decreased expression of IL-32 could significantly inhibit the expression of the invasion-associated proteins MMP-2 and MMP-9 (P<0.05). Conclusion In cervical squamous cell carcinoma,miR-205 is dramatically up-regulated, potentially promoting the proliferation, migration, and invasion of cancer cells, which could further enhance the expression of MMP-2 and MMP-9 through IL-32 up-regulation, and ultimately improve the invasion ability of cervical cancer cells.

Objective To study the effects of semaphorin 3A (Sema3A) on myoblast function and its transcriptional regulation mechanism. Methods Myoblasts were treated with 1.0 µg/ml, 0.1 µg/ml, 0.01 µg/ml recombinant Sema3A protein, and the control group was set up. The proliferation and migration of myoblasts were observed by the IncuCyte system and scratch test. The expression levels of myogenic differentiation factors were detected by RT-qPCR. Transcriptome sequencing was performed for the myoblasts intervened by 1.0 µg/ml recombinant Sema3A protein and those in control group. The differential expressed genes were screened out for GO enrichment analysis. Part of differential expressed genes were verified of transcription level by RT-qPCR. Results IncuCyte cell imaging count showed that Sema3A promoted proliferation of myoblasts, the cell count increased about 17.36% in 1.0 µg/ml Sema3A group than in control group (P<0.001). Scratch test showed the enhanced migration ability of myoblasts by Sema3A, the cell scratch healing rate increased by 69.66% in 1.0 µg/ml Sema3A group than in control group (P<0.001).RT-qRCR showed that during myoblast differentiation, 1.0 µg/ml Sema3A up-regulated the expression of Myf5 by 37.47%±11.67%(P<0.01), and up-regulated the expression of MyoG by 26.57%±11.31% (P<0.05). Bioinformatics analysis showed that Sema3A up-regulated the functional pathway associated with the development and maturation of muscle cells and muscle fibers, bone and chondrocyte proliferation, osteogenic differentiation, and bone mineralization; down-regulated the functional pathway associated with the lipoprotein metabolism and chylomicrons. RT-qPCR verified the partial differentially expressed genes in enrichment pathway, among which the expressions of Prox1 and Myh11 increased by 22.48%±14.42% (P<0.05) and 21.42%±5.81% (P<0.01),respectively; and of LipC and ApoC2 decreased by 23.08%±15.38% (P<0.05) and 55.97%±26.51% (P<0.05), respectively. Conclusion Exogenous Sema3A protein can up-regulate the expression of myoblast differentiation related genes Myf5 and MyoG, and may promote the proliferation and migration of myoblasts by transcriptional regulation of skeletal muscle development,maturation and lipoprotein metabolism.

Objective To investigate the effect of circulatory management strategy with regional cerebral oxygen saturation(rScO₂) and central venous-arterial differential pressure of carbon dioxide (Pcv-aCO₂) as the main targets on the short term prognosis of children with cyanotic congenital heart disease (CCHD). Methods A total of 72 children with CCHD aged 0-1 year,who underwent cardiac surgery under cardiopulmonary bypass (CPB) in the Seventh Medical Center of Chinese PLA General Hospital from October 2020 to June 2021, were selected as research objects, and randomly divided into control group (n=36)and intervention group (n=36). The control group was implemented with traditional circulation management strategy, while the intervention group was implemented the individualized circulation management strategy with rScO₂ and Pcv-aCO₂ as the main targets. The mean arterial pressure (MAP) of endotracheal intubation opening the arteries and veins (T₁), 5 minutes after clipping of ascending aorta (T₂), 5 minutes after opening of ascending aorta (T₃), end of ultrafiltration (T₄), 3 hours after end of CPB (T₅),8 hours after end of CPB (T₆) and 24 hours after end of CPB (T₇) of the two groups of children were recorded, respectively, as well as the pharyngeal temperature (T), hemoglobin (Hb), arterial oxygen saturation (SaO₂), partial pressure of carbon dioxide in artery (PaCO₂), rScO₂, Pcv-aCO₂, arterial blood lactate (Lac) and central venous oxygen saturation (ScvO₂), CPB time, operation time, extubation time, ICU stay time, discharge time, and acute kidney injury (AKI), lung infection, and respiratory failure. Results No significant difference existed in MAP, T, Hb and SaO₂ between the two groups at T₁-T₇ (P>0.05). Compared with control group, PaCO₂ in the intervention group was significantly increased at T₂, T₃, T₆ and T₇, rScO₂ was significantly increased at T₃-T₆(P<0.05), and Pcv-aCO₂ was significantly decreased at T₁-T₇ (P<0.05), Lac levels were significantly decreased at T₃ and T₅ (P<0.05),and ScvO₂ levels were significantly decreased at T₂ and T₃ (P<0.05). No significant difference existed in CPB time, operation time,extubation time, postoperative pulmonary infection and respiratory failure rate between the two groups (P>0.05). The ICU stay time and hospital stay time were significantly shorter in intervention group than in control group [(5.67±1.50) d vs. (7.28±2.11) d,P<0.05; (14.67±3.41) d vs. (19.00±2.63) d, P<0.05], the incidence of postoperative AKI was significantly lower than the control group [25.0% (9/36) vs. 50.0% (18/36), P<0.05]. Conclusion The individualized circulatory management strategy with rScO₂ and Pcv-aCO₂ as the main targets in the perioperative period can significantly improve the short term prognosis of children with CCHD.

Objective To investigate the impact of hyponatremia on the prognosis of neurointensive care patients. Methods A retrospective study of 942 neurointensive care patients admitted to the First Medical Center of PLA General Hospital between August 2010 and May 2020 was performed. We classified these patients into two groups according to serum sodium level within 24 hours of admission: hyponatremia group 233 cases (<135 mmol/L), normonatremia group 709 cases (135-145 mmol/L).The 233 hyponatremia patients were subdivided into two groups: mild hyponatremia group (130-135 mmol/L, n=165) and moderate-severe hyponatremia group (<130 mmol/L, n=68). Primary endpoints were evaluated at 1-month and 6-month respectively with modified Rankin Scale (mRS), mRS scores of 4-6 were defined as poor outcomes. The general clinical data and prognosis were compared between the groups. Logistic regression was used to analyze the influencing factors of patient prognosis. Results Compared with the normonatremia group, the body temperature, blood glucose, urea, and creatinine, diagnosed as cerebrovascular disease, the proportion of poor prognosis at 6 months as well as hospitalization costs in the hyponatremia group were significantly different (P<0.05). There was no significant difference in the prognosis of patients with different degrees of hyponatremia (P>0.05). Multivariate logistic regression showed that hyponatremia, older age, high serum creatinine level, diagnosed as cerebrovascular disease, higher hospitalization costs, and low GCS score were independent risk factor for poor prognosis of NICU patients at 1 month after discharge. And multivariate logistic regression showed that hyponatremia, older age and low GCS score were independent risk factor for poor prognosis of NICU patients at 6 months after discharge. Conclusions Hyponatremia,a common electrolyte disorder in neurointensive care patients, is an independent risk factor influencing prognosis. Even mild hyponatremia may have an impact on outcomes.

Pulmonary hypertension is a clinical syndrome with progressive abnormal increase of pulmonary artery pressure resulting from multiple factors, which eventually leads to patient death by right heart failure. Patients with pulmonary hypertension are often accompanied by pleural effusion clinically and the pleural effusion produced by patients with different types of pulmonary hypertension has its own characteristics. At present, it is widely acknowledged that the occurrence of pleural effusion is closely related to left heart failure, while the relationship between right heart failure and pleural effusion remains controversial. Pulmonary hypertension is an ideal model to study the effects of isolated right heart failure on the development of pleural effusion. This article summarizes the research results of domestic and foreign scholars on pleural effusion related to various types of pulmonary hypertension in recent years, concludes the clinical characteristics, diagnosis and treatment of pleural effusion caused by pulmonary hypertension, describes the hemodynamics, pathophysiology and other mechanisms of pleural effusion and explores the association between the development of pleural effusion and right heart failure. Hoping to be helpful for the diagnosis and treatment of pulmonary hypertension and the study of the relationship between right heart failure and pleural effusion.

Radical hepatectomy is the well-established and highly effective therapeutic tool for early- and middle-stage hepatocellular carcinoma (HCC) to improve the survival. However, the majority of HCC patients in China are not amenable to surgical excision due to the advanced tumor stage at the initial diagnosis. Therefore, it is the bottom line to convert and downstage unresectable tumor into resectable tumor in clinical practice, which is an important means for improving patient survival rate and is currently a clinical research focus as well. In recent years, the rate of conversion surgery for unresectable advanced HCC has achieved dramatic improvement thanking to the accumulating effective therapeutic arsenals, and an increasing number of patients benefit from conversion therapy. Herein, several clinically relevant issues on conversion therapy for HCC were discussed in this review, including the definition of conversion therapy, the optimal selection of patients as well as conversion strategy, and the timing of sequential surgery together with strategy and safety of surgery.