Tuberous sclerosis complex(TSC)is a rare genetic disease that can lead to benign dysplasia in multiple organs such as the skin, brain, eyes, oral cavity, heart, lungs, kidneys, liver, and bones. Its main symptoms include epilepsy, intellectual disabilities, skin depigmentation, and facial angiofibromas, whilst incidence is approximately 1 in 10 000 to 1 in 6000 newborns. This case presents a middle-aged woman who initially manifested with epilepsy and nodular depigmentation. Later, she developed a lower abdominal mass, elevated creatinine, and severe anemia. Based on clinical features and whole exome sequencing, the primary diagnosis was confirmed as TSC. Laboratory and imaging examinations revealed that the lower abdominal mass originated from the uterus. CT-guided biopsy pathology and surgical pathology suggested a combination of leiomyoma and abscess. With the involvement of multiple organs and various complications beyond the main diagnosis, the diagnostic and therapeutic process for this patient highlights the importance of rigorous clinical thinking and multidisciplinary collaboration in the diagnosis and treatment of rare and challenging diseases.

Background::Pulmonary arterial hypertension (PAH) is characterized by excessive proliferation of small pulmonary arterial vascular smooth muscle cells (PASMCs), endothelial dysfunction, and extracellular matrix remodeling. G protein-coupled receptor kinase 2 (GRK2) plays an important role in the maintenance of vascular tone and blood flow. However, the role of GRK2 in the pathogenesis of PAH is unknown.Methods::GRK2 levels were detected in lung tissues from healthy people and PAH patients. C57BL/6 mice, vascular smooth muscle cell-specific Grk2-knockout mice ( Grk2?SM22), and littermate controls ( Grk2flox/flox) were grouped into control and hypoxia mice ( n = 8). Pulmonary hypertension (PH) was induced by exposure to chronic hypoxia (10%) combined with injection of the SU5416 (cHx/SU). The expression levels of GRK2 and Yes-associated protein (YAP) in pulmonary arteries and PASMCs were detected by Western blotting and immunofluorescence staining. The mRNA expression levels of Grk2 and Yes-associated protein ( YAP) in PASMCs were quantified with real-time polymerase chain reaction (RT-PCR). Wound-healing assay, 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay, and 5-Ethynyl-2′-deoxyuridine (EdU) staining were performed to evaluate the proliferation and migration of PASMCs. Meanwhile, the interaction among proteins was detected by immunoprecipitation assays. Results::The expression levels of GRK2 were upregulated in the pulmonary arteries of patients with PAH and the lungs of PH mice. Moreover, cHx/SU-induced PH was attenuated in Grk2?SM22 mice compared with littermate controls. The amelioration of PH in Grk2?SM22 mice was accompanied by reduced pulmonary vascular remodeling. In vitro study further confirmed that GRK2 knock-down significantly altered hypoxia-induced PASMCs proliferation and migration, whereas this effect was severely intensified by overexpression of GRK2. We also identified that GRK2 promoted YAP expression and nuclear translocation in PASMCs, resulting in excessive PASMCs proliferation and migration. Furthermore, GRK2 is stabilized by inhibiting phosphorylating GRK2 on Tyr86 and subsequently activating ubiquitylation under hypoxic conditions. Conclusion::Our findings suggest that GRK2 plays a critical role in the pathogenesis of PAH, via regulating YAP expression and nuclear translocation. Therefore, GRK2 serves as a novel therapeutic target for PAH treatment.

【Objective】 To investigate the feasibility of laparoscopic simple prostatectomy (LSP) in the treatment of large volume benign prostate hyperplasia (BPH). 【Methods】 Clinical and follow-up data of 30 patients with large volume BPH treated with LSP in our hospital during Feb.2019 and Dec.2021 were retrospectively analyzed. All patients underwent extraperitoneal LSP operation. The perioperative and 1-12 month postoperative follow-up data were analyzed. 【Results】 The average prostate volume was (92.4±38.9) mL, operation time (125±45) min, and weight of resected prostate (60.25±16.90) g. The hemoglobin decreased by (12.21±7.25) g/d after operation. No blood transfusion was needed. There was no need for bladder irrigation after operation in 21 cases (70%), and 9 cases (30%) had bladder irrigation time of (0.95±0.49) d. The postoperative catheter indwelling time was (6.92±2.51) d, and hospital stay (5.36±1.63) d. During the follow-up of (9.25±5.4) months, there was 1 case of postoperative intestinal obstruction (Clavien-Dindo grade II), 1 case of transient urinary incontinence (Clavien-Dindo grade I), and 1 case of delayed hematuria (Clavien-Dindo grade I). No urethral stricture occurred. The maximum urinary flow rate (Qmax), post-void residual urine volume (PVR), International Prostate Symptom Score (IPSS) and quality of life (QoL) 3 months after operation were significantly improved compared with those before operation (P<0.05). There was no significant difference in sexual function before and after operation (P>0.05). 【Conclusion】 LSP is safe and effective in the treatment of large volume BPH. It has advantages of complete resection of glands, minor bleeding and short postoperative bladder irrigation time. However, it still needs to be confirmed by a prospective control study of large samples.

Objective To explore the effectiveness of the Five Elements Music Therapy(FEMT)in relieving stress in participants with different cultural backgrounds,and to compare the differences between the FEMT and the Western Art Music Therapy(WAMT)in stress relief.Methods This was a comparative pilot randomized pre-post repeated measures study,37 subjects were allocated with 2 dropped out,with an inclusion-ended sample of 35 subjects,23 from Canada and 12 from China.After informed consent,all subjects were randomly assigned to listening to either Five Elements Music or Western Art Music at home for 30 minutes,twice a week for four weeks.Participants were asked to use headphones,measure their pulse rate before and after each session,and fill out five questionnaires,including a background and demographic survey(reporting age,gender,education,cultural background,listening experience).Self-assessment of stress(pre-post after each session),General Hospital Anxiety/Depression Scale(HADS,weekly after 2nd session),Perceived Stress Survey(PSS,weekly after 2nd session),the Music Therapy Intervention Survey(MTIS,pre-post each session).Results ①There was a significant decrease in self-assessed stress scores after the second session in the FEMT compared with the WAMT group(t=-2.057,P=0.046).②In both groups,there was a significant decrease in stress scores pre-post treatment in each group(WAMT t=5.026;FEMT T=7.645,P=0.000).③There was no significant difference between the two groups in post-intervention HADS scores(P>0.05);In the Chinese sample,there was a significant difference in HADS scores after the eighth session in both FEMT and WAMT groups(t=-3.862,P=0.003),and a statistically significant difference in HADS pre-post intervention in the FEMT((t=5.117,P=0.004).There was a significant difference in MTIS pre-post treatment in the WAMT(t=-2.572,P=0.023),but in not the FEMT group(t= 1.331,P=0.207).Conclusion This pilot trial explores a safe and feasible self-administered music therapy approach for stress in two distinct cultural groups,and for the first time provides preliminary comparison and evidence of effectiveness of FEMT and WAMT in alleviating stress and anxiety.Further investigation with bigger randomized samples is needed to elucidate the effects of different kinds of music and cultural groups on stress and anxiety levels.

Objective The purpose of this study was to investigate the protective effect of dexmedetomidine(DEX)on pathological car-diomyocyte hypertrophy.Methods An in vitro cell population was established in neonatal rats.The rats were divided into six groups:control group(C)without serum for 24 h,model group(A)with angiotensin Ⅱ(Ang Ⅱ)for 24 h,dexmedetomidine group(AD)with Ang Ⅱ+DEX(5μmol/L)for 24 h,C'group with serum-free culture for 48 h,A'group with Ang Ⅱfor 24 h,and AD'group with DEX+Ang Ⅱfor 24 h.The morphological changes of cells were observed by immunofluorescence.The protein expressions of atrial natriuretic peptide(ANP),brain natriuretic peptide(BNP),and myosin heavy chain(β-MHC)were detected by western blot,and the cell activity was detected by CCK-8.Results Compared with group C,the size of cells in group A was larger,and that in group AD was even more significant.Simi-lar observations were found for hypertrophy related proteins.Compared with group C,the expression of ANP,BNP,and βMHC increased in group A,although the increase in AD group was more obvious.CCK-8 detection showed that compared with group C,the activity of group A decreased and that of group AD increased significantly.Compared with the C'group,the expression of hypertrophy-related pro-tein in the A'group was significantly increased,but the expression of ANP and BNP protein in the AD'group was significantly lower than that in the A'group.The differences were statistically significant(P<0.05).Conclusion Dexmedetomidine can alleviate the occur-rence of pathological hypertrophy through compensatory mechanisms similar to physiological myocardial hypertrophy,and may play a role in myocardial protection.

Objective: To explore the efficacy of open reduction and internal fixation in the treatment of senile osteoporotic ankle fractures. Methods: A retrospective case series study was conducted to analyze the data of 26 elderly patients with osteoporotic ankle fractures which all caused by sprain from June 2012 to June 2018 in Changhai Hospital, including 10 male and 16 female patients aged from 60 to 93 years (mean, 69.72 years). In these 26 patients, three had medial malleolus fractures, four had lateral malleolus fractures, six had double ankle fractures and 13 had cotton's fractures. According to the Lauge-Hansen type, all 26 patients can be classified into four types: 5 with supination external rotation type, 4 supination adduction type, 16 with pronation-external rotation type and 1 with pronation abduction type. All the patients received open reduction and internal fixation. Plate fixation was used for lateral and posterior malleolus fractures, plate fixation and cannulated screws were applied to fix the comminuted posterior malleolus fracture while in the comminuted internal malleolus fracture, the steel plate was used only when needed. Early professional functional rehabilitation training and active anti-osteoporosis treatment were applied. All the operation time and bleeding volume were recorded, and the reduction of fracture plus the healing of wounds were observed. At last follow-up, American Orthopedic Foot & Ankle Society (AOFAS) Ankle Hindfoot Scale was used to evaluate the treatment effect and the Visual Analogue Scale (VAS)to evaluate the therapeutic effect and the subjective satisfaction of the patients. Complications were recorded as well. Results: All patients were followed up for 12-48 months (mean, 23.6 months). Operation time ranged from 30 to 95 minutes (mean, 70 minutes) and bleeding volume ranged from 10 to 150 ml (mean, 70 ml). All patients got satisfied reduction of fracture within 25 patients' incision healing in first intention, although one has fat liquefaction. AOFAS Ankle Hindfoot Scale improved from preoperative (84.4±10.8)points to (31.9±11.4)points at last follow-up (P<0.01), and the results were excellent in five patients, good in 17, fair in three and poor in one, with the excellent and good rate of 85%. VAS improved from preoperative(1.85±0.73)points to (9.23±0.28)points at last follow-up (P<0.01). Among 26 patients, 5 with ankle stiffness of different degree recovered after rehabilitation care, and 2 with internal malleolus fractures had bone displacement when receiving rehabilitation care, with no side effect on basic function. No serious complications such as wound infection or skin necrosis were found. Conclusion For osteoporotic ankle fractures in the elderly, open reduction and internal fixation can promote functional recovery and relieve pain.

Objective:To investigate the efficacy of Hebert screw internal fixation of osteoporotic distal humeral coronary fractures in the elderly.Methods:A retrospective case series study was conducted to analyze the data of 26 elderly patients with osteoporotic distal humeral coronary fractures treated in Changhai Hospital from December 2011 to December 2018, including 3 males and 23 females aged 56-84 years (mean, 67.8 years). According to Bryan-Morrey classification, there were 7 patients with type I, 11 with type III, and 8 with type IV. All patients received open reduction and internal fixation. Among the 26 patients, 10 patients with simple humeral head fractures were treated with Hebert screw internal fixation, and 16 patients with humeral head fractures combined with humeral epicondyle fracture were treated with Hebert screw combined with humeral condyle miniplate. Operation time and intraoperative bleeding volume were recorded. At last follow-up, elbow range of motion were measured, and Mayo elbow performance score and visual analog scale (VAS) score were assessed. Meantime, complications were observed.Results:A total of 22 patients were followed up for 6-57 months (mean, 31.8 months). Intraoperative bleeding volume was 100 to 245 ml (mean, 126 ml) and operation time was 60 to 195 minutes (mean, 85 minutes). At last follow-up, the elbow joint flexion was (117.3±4.2)° and extension was (8.2±2.1)°. Mayo elbow performance score improved from preoperative 16.5 (12.8, 24.0)points to postoperative 85.0 (82.5, 92.3)points ( P<0.05). VAS was increased from preoperative (9.6±0.5)points to (2.3±0.2)points at latest follow-up( P<0.05). Two patients had elbow joint stiffness after operation and recovered after functional exercise. One patient had bone displacement when receiving rehabilitation care, which did not affect the function, and hence no further treatment was given. All patients had no infection or skin and soft tissue complications after surgery. Conclusions:For osteoporotic distal humeral coronary fractures in the elderly, Hebert screw internal fixation is effective in facilitating function recovery and relieving pain. When the fracture is combined with lateral humeral condyle fracture, additional plate fixation can be used for rigid stabilization.

Objective: To examine the association of abnormal metabolic indexes and its clustering with carotid intima-media thickness (cIMT) in childhood. Methods: A convenient sampling method was used to conduct a cross-sectional survey from November 2017 to January 2018 in a primary school in Huantai County, Zibo City, Shandong Province. A total of 1 240 children who had complete data of questionnaires, physical examinations, and blood biochemical tests were included for analysis. Covariance analysis was used to analyze the association of the single abnormal metabolic indices and its clustering with cIMT. The multivariable linear regression model was used to quantify the relationship between the number of abnormal metabolic indices and cIMT. Results: The age of 1 240 children was (8.9±1.5) years, and 657 boys accounted for 53.0%. The highest detection rate of abnormal metabolic indicators was found in abdominal obesity, accounting for 30.9% (203/657) of boys and 29.7% (173/583) girls respectively.The cIMT of boys and girls were (0.49±0.08) and (0.45±0.07) mm, respectively. After adjusting for sex, age, consumption of fruits, vegetables and carbonated drinks, sleep duration, screen time and physical activity, abdominal obesity, elevated blood pressure, total triglyceride and fasting glucose were associated with cIMT (all P values <0.001). Children with 0, 1, 2 and ≥3 abnormal metabolic indicators had cIMT values of (0.45±0.07), (0.48±0.08), (0.50±0.09) and (0.53±0.08) mm, respectively. That was, cIMT values increased with the number of abnormal metabolic indexes (P_trend<0.001). Conclusion Abdominal obesity, elevated blood pressure, total triglyceride, fasting glucose and clustering of the above factors are associated with cIMT.

Objective To investigate clinicopathological features of pancreatic carcinoma with or without lymph node metastasis,and to explore the relationship between the lymph node metastasis and the prognosis of pancreatic carcinoma.Methods The clinical and follow up data of 216 patients with pancreatic carcinoma from 2001 to 2015 were retrospectively analyzed.Kaplan-Meier method was used to estimate survival rates and plot survival curves.Results The postoperative survival time was 4-86 months,the median survival time was 19 months,and the postoperative 1,3 and 5 year survival rates were 65.1％,33.8％,20.5％,respectively.Patients with positive lymph node metastasis were with 1,3,5 year survival rates of 36.5％,12.2％,0％,those with no lymph node metastasis were with 1,3,5 year survival rates of 70.3％,38.0％,21.4％ (x2 =15.803,P ＜ 0.001).Conclusions Lymph node metastasis in patients with pancreatic cancer is worse than that without lymph node metastasis.Lymph node metastasis is one of the main prognostic factors in patients after radical resection of the pancreatic cancer.

Objective To investigate the density of bladder pacemaker cells (ICC) in prostatic hyperplasia with detrusor underactivity (PDU) and the impact of stress environment on its growth. Methods 23 PDU guinea pig models and 26 pigs for control (BPH, n = 6; normal group, n = 20) were developed. After water-filled urodynamic pressure measurement of bladder for three groups , detrusor tissue was made into frozen sections. TheICC numberwere measured with immunofluorescence stainingand observed by confocal microscopy. Further ICC cells in vitro were cultured under stress environment and its counts were analyzed by colony formation assay. Results Decreased density of ICC was observed in PDU group (0.28 ± 0.52)% compared to control [(5 ± 0.36)%,P < 0.05] and the BPH group (5.4% ± 0.42)%, P < 0.05). The ratio of dimer and monomer [(6.13 ± 1.45)%] in PDU group was significantly lower than those of the control [31.55 ± 9.67)%, P < 0.05] and the BPH group [(71.52 ± 8.95)%, P < 0.05]. There is a negative correlation between the density of ICC in vitro and duration of stress. By contrast , there is a positive correlation between the density of ICC and incubation time after the stress is removed. Conclusion Distribution of decreased density of ICC is involved in the pathogenesis of PDU , which may be due to long-term stress environment. Thus eliminating stress environment may help restore ICC density in PDU.