Objective To explore the safety and efficacy of laparoscopic left renal vein stent implantation combined with microsurgical varicocelectomy in the treatment of nutcracker syndrome complicated with varicocele.Methods A retrospective analysis was conducted on the data of 50 patients with nutcracker syndrome complicated with varicocele admitted to our hospital during Nov.2018 and Jul.2023.All patients underwent laparoscopic left renal vein stent implantation combined with microsurgical varicocelectomy.Results Altogether 47 patients were followed up after operation,with a mean age of(21.45±3.84)years.All operations were successful,and gross hematuria,proteinuria,abdominal pain and other symptoms relieved within 3-7 days after surgery.Postoperative follow-up showed that no patients had serious complications or recurrence of clinical symptoms.Left renal vein ultrasound and CT showed that the blood flow of the left renal vein was restored,and the stent position was stable.Compared with those before surgery,the angle between the abdominal aorta and the superior mesenteric artery[(44.91±6.59)° vs.(22.58±6.61)°]and the diameter of the left renal vein at the angle[(6.03±0.99)mm vs.(1.87±0.46)mm]were significantly increased,and the blood flow velocity of the left renal vein at the angle[(48.77±14.79)cm/s vs.(102.53±41.15)cm/s]was significantly decreased,with statistically significant differences(P＜0.001).Scrotal ultrasound confirmed that there was no recurrence of varicocele 6 months after surgery,and the diameter of the spermatic vein was significantly reduced,with statistically significant differences(P＜0.001).Semen analysis showed that the sperm concentration[(60.27±48.45)×106/mL vs.(36.57±36.67)×106/mL,P=0.032]and percentage of rapid forward movement of sperm were significantly increased[(22.54±10.70)vs.(15.01±10.77),P=0.005],with statistically significant differences.The increase value of semen concentration[(23.7±41.48)×106/mL vs.(6.12±4.97)×106/mL,P=0.016)]increased after combined operation compared with left renal venous stenting alone,and there was no significant difference in the diameter of spermatic vein,inner diameter of renal vein and flow rate between the two surgical methods(P＞0.05).Conclusion Laparoscopic left renal vein stent implantation combined with microsurgical varicocelectomy is a minimally invasive,safe and effective method for the treatment of nutcracker syndrome complicated with varicocele.

【Objective】 To explore a new treatment of primary bilateral macronodular adrenal hyperplasia (PBMAH) and its efficacy. 【Methods】 Clinical data of 20 PBMAH patients treated in our hospital during Mar.2010 and Apr.2021 were retrospectively analyzed. All patients underwent laparoscopic subcutaneous displacement of vascularized adrenal. The clinical symptoms, plasma free cortisol, adrenocorticotrophic hormone (ACTH), and 24 h urinary free cortisol were regularly monitored after surgery. 【Results】 Of all 20 patients, 19 were followed up for 18 to 120 months (median 60 months). Three months after surgery, reexamination showed 1 patient had decreased plasma free cortisol and increased ACTH, but had no symptoms of low corticosteroids. After another 3 months, the plasma free cortisol and ACTH returned to normal. After 4 to 48 months, the parameters recovered in all patients and the clinical symptoms disappeared. 【Conclusion】 Laparoscopic vascularized adrenal displacement is a new and effective method for the treatment of PBMAH. It can alleviate the Cushing syndrome with no obvious adverse reactions.

Objective To investigate the mechanisms of miRNA-15a and miRNA-16 in the process of reversing cisplatin resistance in ovarian cancer.Methods Human ovarian cancer cisplatin-resistant cell lines CoC1/DDP were transfected with miRNA-15a and miRNA-16 mimics and treated with cisplatin.qRT-PCR was used to detect the expression levels of miRNA-15a and miRNA-16 in normal CoC1/DDP cell group,cisplatin treated group,negative control group,miRNA-15a transfected group,miRNA-16 transfected group and overexpressed Bmi-1 plasmid.Western blot was used to detect the expression level of Bmi-1 in each group,CCK-8 and Annexin V/PI were used to detect cell survival and apoptosis,and γ-H2AX immunofluorescence was used to detect cell apoptosis.Results The CoC1/DDP ovarian cancer cell line shows low expression of miRNA-15a and miRNA-16,and high expression of Bmi-1 protein,which makes it resistant to cisplatin.When the levels of miRNA-15a and miRNA-16 are overexpressed,the Bmi-1 protein decreases(P<0.05),leading to a decrease in cell survival rate(P<0.05),a significant increase in DNA apoptosis(P<0.05),and more severe DNA damage(P<0.05).Overexpression of Bmi-1 plasmid can increase cell viability(P<0.05)and reduce the rate of cell apoptosis(P<0.05).Conclusion The Bmi-1 protein may be a target for the regulation of miRNA-15a and miRNA-16,and overexpression of miRNA-15a and miRNA-16 can increase the sensitivity of ovarian cancer cells to cisplatin by reducing the Bmi-1 protein.This provides a new idea for predicting molecular markers of cisplatin resistance in ovarian cancer and overcoming drug resistance targets in ovarian cancer.

As a powerful attempt by government to promote the construction of the multi-level healthcare security system and social and commercial integration in China, " City-customized Medical Insurance" still has many problems to be solved at the beginning of its development, such as unclear boundary between government and enterprises, limited coverage and strength of security. On the basis of clarifying the current situation of " City-customized Medical Insurance", and combing the management experience of social and commercial integration in Medicare Part C plan of the United States, the authors put forward that China should make full use of the advantages of the combination of promising government and efficient market, guide differentiated product design, and establish market access and evaluation mechanism, so as to promote the effective connection between China′s commercial health insurance and basic healthcare insurance, and further reduce the people′s medical burden.

Objective:To study the neuroprotective effect of nobiletin on the symptoms of postoperative cognitive impairment (POCD) induced by sevoflurane inhalation.Methods:Twenty-four aged SD rats (12 female mice and 12 male mice) were divided into three groups randomly: control group ( n=8), surgery group ( n=8) and surgery + nobiletin group ( n=8), with 4 females and 4 males in each group.The rats in surgery group and surgery+ nobiletin group were given normal saline(0.1 ml/10 g, once a day) and nobiletin(100 mg/kg, once a day) intragastrically for 6 weeks.Then the rats were anesthetized by sevoflurane and treated by abdominal exploration surgery, and then continued gavage for 1 week.The rats in control group were given normal saline(0.1 ml/10 g, once a day) intragastrically for 7 weeks without anesthesia or surgery.Sevoflurane inhalation anesthesia and abbreviated laparotomy were not done for control group.Morris water maze and open field experiment were used to measure the memory and cognitive ability and the independent exploration ability respectively.The changes of α-band electroencephalogram (EEG) were recorded by multi-channel physiological signal acquisition and processing system.The concentration of S100β, a marker of neurological impairment was detected by ELISA.Western blot was used to detect the expression level of IBA-1 in microglia.SPSS 20.0 software was used to analyze the data. Results:There were no significant differences in Morris water maze, positioning cruise test and open field test among the groups before operation (all P>0.05). The differences were statistically significant among the groups 7 days after operation (all P<0.05). Compared with the control group (the escape latency, path length and cross platform times were ((20.37±1.11)s, (552.37±14.19)cm, (6.75±0.43)times respectively), the escape latency ((40.87±2.03)s) and path length ((1 258.62±19.53)cm) of rats in surgery group were significantly longer (both P<0.01), and the cross platform times ((2.12±0.33)times) significantly reduced ( P<0.01). The differences between surgery + nobiletin group ((22.37±1.11)s, (584.50±10.90)cm, (6.62±0.48)times) and control group were not significant (all P>0.05). The open field experiment showed that the movement distance, the crossed square number, and activity times in surgery group ((1.78±0.55) m, (4.75±0.50), (14.87±0.33) times) decreased significantly compared with those in control group ((3.73±0.07) m, (11.10±0.78), (51.12±0.78) times, all P<0.01). No significant difference was found between surgery + nobiletin group ((3.76±0.07)m, (10.75±0.66), (50.75±0.43)times) and control group(all P>0.05). Before anesthesia, there was no significant difference in the power ratio of α-band among the three groups ( P>0.05), but the differences during anesthesia and operation were significant ( F=72.58, 101.50, P<0.01). During anesthesia and operation, the power ratio of α-band in anesthesia and in surgery group (2.51±0.04, 2.14±0.03) were significantly lower (both P<0.01) than those in control group (3.49±0.03, 3.49±0.03), while there was no obvious changes (both P>0.05) in the surgery + nobiletin group (3.50±0.04, 3.51±0.04). There were significant differences in Bcl-2 protein expression and caspase 3/7 protein activity among the three groups ( F=5.21, 7.84, P<0.01). Compared with control group (1.00±0.02, 1 557.46±3.63), Bcl-2 of rats in the surgery group(0.40±0.05) were significantly lower and Caspase3/7 expression of surgery group (3 689.58±10.46) was significantly higher (both P<0.01), while the rats in the surgery + nobiletin group had no significant difference in both Bcl-2 level (1.03±0.06) and caspase 3/7 activities (1 805.28±6.17, both P>0.05). The difference of S100 β protein expression was significant among the three groups ( F=490.80, P<0.01). Compared with the control group ((0.18±0.01)μg/L), the concentration of S100β protein in the surgery group ((2.13±0.02)μg/L) decreased ( P<0.01), while there was no significant difference in the surgery + nobiletin group ((0.16±0.01) μg/L, P>0.05). The expression levels of IBA-1 protein ( F=10.83) and TNF-α, IL-1, IL-1β and IL-6 ( F=996.20, 221.40, 73.02, 174.13) were significantly different among the three groups (all P<0.01). The expression level of the neuroglial marker IBA-1 in the surgery group(1.36±0.02) was significantly higher than that in the control group (1.00±0.01, P<0.01), while the surgery + nobiletin group (1.03±0.01) had no significant different compared with control group ( P>0.05). The levels of inflammatory factors, including TNF-α, IL-1, IL-1β and IL-6, in the brain of rats treated with nobiletin ((49.06±3.63)pg/mg, (2.09±0.43)pg/mg, (16.27±0.80)pg/mg, (2.11±0.19)pg/mg) were significantly lower than those in the surgery group((145.10±6.46)pg/mg, (5.67±0.43)pg/mg, (27.88±3.43)pg/mg, (4.74±0.32)pg/mg, all P<0.01). Conclusion:Nobiletin can obviously alleviate POCD symptoms caused by sevoflurane inhalation anesthesia.

Objective:To evaluate the changes in electroencephalogram (EEG) during cognitive dysfunction induced by multiple inhalation of sevoflurane anesthesia in aged rats.Methods:Twenty-one SPF healthy male Sprague-Dawley rats, aged 20-22 months, weighing 450-550 g, were divided into 2 groups using a random number table method: control group (group C, n=8) and repeated inhalation of sevoflurane anesthesia group (group S, n=13). In group S, the rats were put into an anesthesia box and inhaled a mixture of 3% sevoflurane and 30% oxygen for anesthesia, the oxygen flow rate was set at 3 L/min, maintaining for 3 h, and anesthesia was performed once every week for 3 times in total.The rats only inhaled a mixture of 70% air and 30% oxygen in group C. Two weeks later, cognitive function was assessed using Morris water maze test, the EEG was collected and analyzed by the multi-channel physiological signal system, and the recording time of EEG signal was 30 min.The rats were sacrificed, and the brains were collected for determination of the count of apoptotic nerve cells (by TUNEL staining), and the apoptotic rate of nerve cells was calculated. Results:Compared with group C, the escape latency was significantly prolonged at 3rd and 4th days of training, the number of crossing the original platform was decreased at 5th day, the percentage of high-frequency waves was decreased, the percentage of low-frequency waves was increased, and the apoptosis rate of nerve cells was increased in group S ( P<0.05). Conclusion:The percentage of high-frequency waves is decreased, and the percentage of low-frequency waves is increased during cognitive dysfunction induced by multiple inhalation of sevoflurane anesthesia, which may be related to apoptosis in nerve cells of aged rats.

A 87-day-old female patient presented with patchy erythema on the right body and ipsilateral limb deformity after birth, and visited the hospital in January 2012. Skin examination showed obvious red plaques on the right lower abdomen, right buttock, right perineum, right leg and right foot, with yellow scales on the surface and clear boundaries, and there was no obvious exudation or odor; pale yellow verrucous hyperplasia was observed on the right lower jaw, right neck, right axilla, and on the back of the first to fourth fingers of the right hand; only 1 interphalangeal joint and no nail plate was observed on the second, third and fourth toes of the right foot. The X-ray of the right foot showed deformity and bone defects. The patient was diagnosed with CHILD syndrome, and treated with intermittent oral acitretin capsules, and topical vaseline ointment, tacalcitol ointment and weak-potency glucocorticoid ointment for more than 6 years. The skin lesions regressed during treatment, but occurred repeatedly after withdrawal. Thereafter, the patient was switched to simvastatin ointment for 2 years. The skin lesions increased proportionally with the increase of age, and the affected limb grew a little more rapidly than the healthy limb. By January 2020, the skin lesions on the right lower jaw, right neck, and the first to fourth fingers of the right hand had subsided, but new band-like hypertrophic verrucous plaques occurred on the fifth finger of the right hand; the skin lesions on the right leg were slightly improved, and no involvement of other systems was observed.

Objective: To evaluate the expression of p-AKT and p-mTOR, the key proteins in PI3K/AKT/mTOR pathway in pediatric Burkitt lymphoma (BL), and to investigate the clinical and prognostic significance. Methods: Fifty-eight cases of pediatric BL and thirty cases of reactive hyperplastic lymphadenitis (RH) were collected at Children′s Hospital of Fudan University from September 2011 to July 2018. Paraffin sections of tissues were immune stained for p-AKT and p-mTOR, and the expression was assessed and correlated with the clinical features and prognosis. Results: A total of 58 cases were diagnosed and 6 cases lost the follow-up. Of the remaining 52 BL patients including 43 males and 9 females, the median age was 5 years (range: 2 to 14 years). Regarding to the correlation between the two biomarkers, Spearman test showed that p-mTOR was positively associated with the expression of p-AKT (r=0.759, P<0.001). Of all BL patients, the positive rates of p-AKT and p-mTOR were 62.1% (36/58) and 60.3%(35/58) respectively, both significantly higher than control group (P=0.011, P=0.035 respectively). The presence of p-AKT was significantly associated with higher lactate dehydrogenase (LDH≥573 IU/L) level in patients of the disease (P=0.006), while p-mTOR was increased both in the higher LDH and lower ratio of albumin to globulin (A/G) group (P=0.006, P=0.034 respectively). Expression of p-AKT and p-mTOR did not show any statistical correlation with sex, age, St.jude stage, tumor size, B-symptom present or not, number of extra-nodal sites or international prognostic index (IPI) (P>0.05). Fifty-two patients had a median follow-up of 40 months (range: 5-87 months). Univariate analysis showed that p-AKT expression was significant in predicting both inferior OS (5-year estimate, 72.7% vs. 94.7%, χ²=4.123, P=0.042) and PFS (5-year estimate, 66.7% vs. 94.7%, χ²=5.822, P=0.016). The 5-year OS rate was 71.0% (22/31) for the p-mTOR positive cohort of patients compared to 95.2% (17/21) for p-mTOR negative group (χ²=4.881, P=0.027); however, there was no statistical significance in 5-year PFS rate (P>0.05). Especially, the 5-year OS and PFS rate of p-AKT/p-mTOR double-positive group were significantly lower than negative control group (including absence of single p-AKT or p-mTOR expression, and absence of both) (OS: 69.0% vs. 95.7%, χ²=6.285, P=0.012; PFS: 65.5% vs. 91.3%, χ²=5.405, P=0.020). The results of multivariate COX proportional risk regression analysis indicated that p-AKT/p-mTOR double-positive, higher LDH and IPI score 3-5 were independent prognostic factors for both OS and PFS, and the bulky tumor (>10 cm) for PFS of pediatric BL. Conclusion The expression of p-AKT and p-mTOR may be a potential reference for diagnosis and the independent prognostic indicators of pediatric BL.

Objective: To analyze the clinicopathological features, immunohistochemical (IHC) phentotype,diagnosis and differential diagnosis of infantile/congenital fibrosarcoma (IFS/CFS) with unusual histological features. Methods: Five IFS/CFS at Children′s Hospital of Fudan University from March 2014 to July 2018 were analyzed for their diagnosis and differential diagnosis. Results: Two cases were males, three cases were females. The clinical manifestation of IFS/CFS was a rapidly-growing and painless mass. There were no specific radiologic features. Histologically, the tumor cells are arranged in intersecting or sheet-like patterns. There were focal hemangioma-like areas in four cases. There were also focal areas of primitive asteroid, short-spindled, and oval tumor cells in three cases. IHC study showed the tumor cells diffusely expressed TLE1(2/5), Vimentin(5/5), and WT1(3/5), in a cytoplastic pattern; they focally expressed CD34(3/5), CD31(3/5), and α-SMA(2/5). Fluorescence in situ hybridization (FISH) detected break-apart positivity of ETV6 gene. Conclusions Hemangioma-like pattern, myxoid area, and TLE1 expression is very rare in IFS/CFS. Detection of ETV6 gene break-apart by FISH is very helpful in the diagnosis and differential diagnosis of IFS/CFS.

Objective: To investigate the clinicopathological features, diagnosis, differential diagnosis, treatment and prognosis of pediatric alveolar rhabdomyosarcoma (ARMS). Methods: The clinical and pathological data of 25 pediatric ARMS from 2008 to 2018 in Children′s Hospital of Fudan University were collected. This histomorphology was assessed, and FOXO1 gene rearrangement was detected with FISH. The treatment details and outcome were analyzed. Results: There were 13 males and 12 females, with ages range from 19 days to 14 years (median 6 years, mean 6.2 years). The ARMS were located in the limbs (13 cases), head and neck (4 cases), trunk (3 cases), abdominal cavity (3 cases), scrotum (1 case) and perianal region (1 case). The ARMS were classified histologically as classic group (18 cases), solid group (5 cases) and embryonic-alveolar mixed group (2 cases). The typical pathological characteristics were small dark round cells arranged in solid, glandular and papillary patterns. The tumor cells expressed ALK (D5F3) (21/25, 84.0%), muscle origin DES (23/25, 92.0%), myogenin (22/25, 88.0%), MYOD1 (19/25, 76.0%), and in some cases they also expressed neurogenic marker Syn (6/25, 24.0%). FOXO1 gene rearrangement was detected by FISH in 24/25 cases (96.0%). Conclusion Pediatric ARMS is rare and has unique clinicopathological characteristics, and needs to be differentiated from other common small round cell malignancies in children. ALK, DES, myogenin, MYOD1 immunohistochemistry and FOXO1 gene rearrangement are valuable aid in the diagnosis of ARMS.