Volume 100 ·  Issue 22 ·  2020

To investigate the novel genetic cause associated with hypospadias and the strategy for preventing offspring genetic defects in these patients.

In March 2019, a patient with gonadal dysplasia (hypospadias associated with cryptorchidism) was referred to Shanghai General Hospital. His secondary sex characters, level of sex hormones and the development of male reproductive system was assessed through physical examination, sex hormone examination, male reproductive system B-ultrasound and computed tomography (CT). Whole-exome sequencing (WES) was preformed to investigate the pathogenic genetic variations associated with hypospadias and cryptorchidism. Also, Sanger sequencing was conducted to verify the WES results in the pedigree. Semen analysis was used to assess the fertility of the proband and the SRD5A2 gene analysis of his spouse was performed to assess the risk of genetic defects in the offspring.

The patient suffered from gonadal dysplasia (hypospadias associated with cryptorchidism). Physical examination showed an inverted triangular distribution of pubic hair, small penis and the volume of the testis was 8 ml. Sex hormone examination revealed the level of FSH, LH, Pituitary prolactin (PRL), estrogen (E₂), testosterone (T), and sex hormone-binding globulin (SHBG) was 25.81 U/L, 10.84 U/L, 21.09 μg/L, 153 pmol/L, 16.95 nmol/L, and 36.15 nmol/L respectively. B-ultrasound and computed tomography (CT) showed left inguinal testis. Also, semen analysis illustrated that the volume was 0.05 ml and sperm concentratio n<2×10⁶/ml, suggesting oligospermia in this case. WES sequencing and Sanger sequencing showed compound heterozygous LoF mutations in SRD5A2 [NM_000348.3:C.679C>T(p.Arg227Ter) and NM_000348.3:C.16C>T(p.Gln6Ter)] in this patient. And there were no pathogenic genetic variations of SRD5A2 in the spouse.

Novel compound heterozygous LoF mutations in SRD5A2[NM_000348.3:C.679C>T(p.Arg227Ter) and NM_000348.3:C.16C>T(p.Gln6Ter)] may be the primary cause of disorders of sex development.

To investigate the therapeutic effect of simple tunica albugineaincision and ventral penile lengthening surgery on the correction of penile curvature due to asymmetry of the cavernous bodies in hypospadias.

A retrospective analysis was performed in 39 children with hypospadias who underwent simple tunica albuginea incision and ventral penile lengthening surgery for correcting asymmetry of the cavernous bodies from January 2016 to December 2018(36 of them were from Department of Pediatric Urology surgery, The Children′s Hospital, Zhejiang University School of Medicine, and 3 from Department of Urology surgery, Affiliated Hospital ofJiaxing University), all of whom aged from 0.5 to 5, with a median age of 1.1 years. During the first stage of the operation, firstly penile skin and sarcoma was released by completely degloving the skin and fascia of penis, secondly the factor of short urethral plate was solved by transection of urethral plate, and then the dorsal length of penis (A), the ventral length of the penis before and after straightening by incision of tunica albuginea (B and C) were measured and recorded; onto the second stage of the operation, an artificial erection test was performed to observe the curvature of the penis, the dorsal and ventral length of the penis (D and E) were measured. The dorsal and ventral length of the penis before and after straightening were compared.

The dorsal length of penis (A) was 33-39(35.6±3.2) mm, the length of ventral length of penis before straightening (B) was 28-35 (29.8±2.8) mm and the length of ventral length of penis after straightening (C) was 32-38 (34.3±2.1) mm, which were measured during the first stage of operation, and the difference between B and C was statistically significant (P<0.05), while the difference between A and C was not statistically significant (P>0.05). The dorsal length of penis (D) was34-41 (36.4±2.5) mm and the ventral length of penis (E) was 33-40 (35.7±3.6) mm, which were measured during the second stage of operation, and there was no significant difference between D and E (P>0.05). The degree of penile curvature at the time of erection was less than 15° by measuring with the side photos in all patients during 0.5 to 2.5 years of follow-ups with an average of 1.7 years.

Penile curvature due to the asymmetry of the cavernous bodies could be effectively corrected by simple incision of ventral tunica albuginea, which showed a good result of early follow-up. The effect of this surgery on ventral penile straightening could be verified by measuring and comparing the ventral and dorsal length of penis during surgery.

To explore the significance of penile index in the diagnosis of concealed penis and the evaluation of therapeutic efficacy.

A retrospective study was conducted on 221 children with phimosis and 113 children with concealed penis aged 6-10, all of whom had undergone circumcision or phalloplasty respectively in Shanghai Children’s Medical Center from January 2014 to December 2017. Penile index was measured before and after surgery. The values of phimosis and concealed penis were tested by group t test. Self -control test was performed for values of concealed penis before and after operations.

Penile index was 0.78±0.08 in children with phimosis. It was 0.23±0.10 in concealed penis before operation and changed to 0.84±0.11 postoperatively. In children with phimosis and concealed penile, the difference of penile index was statistically significant (P<0.001). The difference of penile index before and after operation was statistically significant (P<0.001) in children with concealed penis.

Penile index is an effective index to evaluate the degree of penis exposure.

To evaluatethe clinical efficacy and complications of skin graft and flap plastic technique covered the defect in perineal Paget′s disease postoperatively.

The study comprised 6 patients diagnosed with perineal Paget′s disease at Beijing Chao-Yang Hospital from June 2017 to July 2019, with all available clinical data reviewed. The defects after resection of lesions were reconstructed with skin graft, advancement skin flap during the operation, respectively. The operation time, the skin graft or flap survival situation, intraoperative and postoperative complications were recorded.

Of all 6 patients, Ray stage A1consisted of 1 case, A2 5 cases. The age was (68±9) years, the hospitalization time was (14.8±8.1) days, the BMI was (25.6±3.7) kg/m², the operation time was (132.0±80.7) min, and the average blood loss was (18.3±11.7) ml. Five cases was with Paget′s disease, and 1 case with skin adenocarcinoma with Paget′s disease were diagnosed by pathology. The defects of 4 cases and 2 cases after removal of the tumor were reconstructed with scrotal advancement skin flap and skin graft, respectively. The skin graft and flap survived well during afollow-up of (15.3±8.1) months.There has been no local recurrence. The foreskin edema and wound infection were noted in 4 cases and 1 case, respectively. There was no other related complications.

Perineal Paget′s disease can be managed by resection and immediate reconstruction with skin graft or flap according to the size and location of the defect, and the clinical efficacy is distinct.

To explore the value of right heart contrast echocardiography in etiological diagnosis and severity assessment of pulmonary hypertension (PH).

A retrospective analysis was conducted on 74 patients who underwent transthoracic contrast echocardiography in China-Japan Friendship Hospital from May 2015 to July 2018, all of whom were diagnosed as PH by right heart catheterization. Patients were divided into three groups according to contrast echocardiography: the intra-cardiac shunt group (<4 cardiac cycles with microbubbles in the left heart); Intrapulmonary shunt group (>4 cardiac cycles with microbubbles in the left heart); non-shunt group. The etiology, partial arterial oxygen pressure (PO₂), N-terminal pro-brain natriuretic peptide (NT-proBNP), mean pulmonary artery pressure (mPAP), right atrial pressure (RAP), pulmonary vascular resistance (PVR) and cardiac output (CO) were analyzed. Central nervous system complications were also compared among the three groups.

Among the 74 patients, right-to-left shunt was found in 28 cases (37.8%) by contrast echocardiography, including 11 cases (14.9%) of intra-cardiac shunt and 17 cases (23.0%) of intrapulmonary shunt. In the 11 cases of intra-cardiac shunt, 7 were diagnosed with congenital heart disease and 4 were patent foramen. Two with hereditary hemorrhagic telangiectasia (HHT) and 1 with pulmonary arteriovenous malformation (PAVM) were included in the 16 cases of intrapulmonary shunt. There was no statistical difference in PO₂, mPAP, PVR, NT-proBNP, RAP, CO and functional class among the three groups (all P>0.05). A total of 5 cases (6.8%) were found with nervous system comorbidities, 4 cases (5.4%) with cerebral infarction and 1 cases epilepsy, and 2 cases of cerebral infarction were diagnosed as paradoxical embolism. Nervous system complications were more common in patients with intra-cardiac shunt than in other groups.

While right-to-left shunt detected by contrast echocardiography has no relationship with disease severity, it has complementary value in the etiological diagnosis of PH, and intra-cardiac shunt may increase the risk of nervous system complications.

To analyze the clinical characteristics and long-term prognosis of implantation of drug-eluting stents (DES) for elderly patients with unprotected left main artery (ULM) disease.

A total of 414 patients (327 males and 87 females) who underwent DES implantation were enrolled in the Department of Cardiology, Beijing Anzhen Hospital from January 2005 to March 2010, with a mean age of (61.5±10.7) years old. The patients were divided into two groups according to age: 300 cases in the group of age <70 years old, and 114 cases in the group of age ≥70 years old. The clinical characteristics and long-term prognosis of two groups were compared.

In the group of age ≥ 70 years old, the proportion of female was higher (31.6% vs 17.0%, P=0.001) and the incidence of chronic total occlusion (CTO) (P=0.020), hypertension (P=0.018) and cerebrovascular disease (P=0.013) were higher than those in the group of <70 years old. All-cause mortality and cardiac mortality were also higher than those in the group of <70 years old ( P=0.025, P=0.013). The follow-up period was (21.4±9.6) months. After adjusting for multiple clinical factors, there were no statistical differences of incidence of the total major adverse cardiac and cerebral events (MACCE), myocardial infarction, cerebrovascular events, and revascularization recurrence between the two groups. But all-cause mortality (HR=3.790, 95%CI: 1.271-11.298, P=0.017) and cardiac mortality (HR=17.424, 95%CI: 2.440-124.410, P=0.004) in the group of age ≥70 years old were still remarkably higher than those in the group of <70 years old.

Age is an independent risk factor for increased mortality after DES stent implantation in ULM disease. DES stent implantation in age ≥70 years old patients with ULM disease is considered feasible, but it needs to be treated with caution.

To assess structural changes in retina after systemic immunosuppressive treatment in Vogt-Koyanagi-Harada (VKH) disease using spectral-domain optical coherence tomography (SD-OCT).

The clinical data of 17 VKH cases (34 eyes) who consecutively attended the Beijing Tongren Hospital between December 2015 and December 2019 were retrospectively reviewed. All the patients had acute or subacute onset, and underwent high-dose systemic corticosteroid and/or immunosuppressive treatment, with a followed-up time of at least 6 months. At the end of follow-up, the intraocular inflammation was controlled, and oral prednisone was withdrawn or being adjusted to less than 10 mg/day. The SD-OCT features of the included eyes were analyzed before treatment, 1 week, 1 month and 3 months after treatment, and at the last visit.

A total of 17 cases (34 eyes; 6 males and 11 females) were included, with an age of (42.2±10.6) years, and were followed up for (9.4±3.3) months. At 1 week after initiating treatment, the percentage of the eyes with extensive/multiple or multifocal retinal detachment in the macular region, membranous structures and intraretinal cysts, and undulations and bumps of retinal pigment epithelium (RPE) decreased (5.9% vs 100%, 2.9% vs 47.1%, 5.9% vs 70.6%, 11.8% vs 58.8%, respectively, all P<0.001). There was statistical significant difference of the percentage of ellipsoid zone and external limiting membrane (ELM) disruptions before treatment, at 3 months and the last visit (100% vs 35.3%, 64.7% vs 52.9%, 41.2% vs 26.5%, respectively, allP<0.001). At the last visit, there were statistical significant differences of the best corrected vision acuity (BCVA) between the intact ellipsoid zone group (20 eyes) and the discontinuous group (14 eyes), as well as between the intact ELM group (25 eyes) and the discontinuous group (9 eyes), respectively [0 (0, 0.05) vs 0.10 (0.03, 0.33) (log MAR),P=0.004; 0 (0, 0.07) vs 0.22 (0.05, 0.40) (log MAR), P=0.005].

The edema of choroid and retina subsided obviously at 1 week after initiating treatment. The extent of damage and recovery ability of ellipsoid zone and ELM were different before treatment, at 3 months and the last visit. At the last visit, the outer retinal layers failed to recover completely in some patients, and were related to the BCVA.

To assess the effectiveness of bronchial thermoplasty (BT) in "real-world" patients with severe asthma at 2 years post therapy.

Outcomes of 70 patients with severe asthma undergoing bronchial thermoplasty from March 2014 to November 2017 in China-Japan Friendship Hospital were retrospectively analyzed two years post therapy. The scores of Asthma Control Test (ACT) and Mini Asthma Quality of Life Questionnaire (mini-AQLQ), the number of severe exacerbations, emergency department visits and hospitalizations for asthma symptoms in the past year, indicators of pulmonary function including forced expiratory volume in one second (FEV₁), FEV₁ as a percentage of predicted value (FEV₁%pred) and FEV₁/forced vital capacity (FEV₁/FVC), maintenance asthma medications, the cost of asthma drugs and the total annual cost of asthma treatment were evaluated and analyzed before and 2 years after BT therapy, and the subjective assessment about effectiveness of BT were given by the patients.

Before and 2 years after BT, the numbers of subjects suffering severe exacerbations in the past year were 70 (100%) and 37 (52.9%), and the numbers of total severe exacerbations were 575 and 162 respectively. The numbers of patients having emergency department visits due to asthma exacerbation were 46 (65.7%) and 9 (12.9%), and the numbers of emergency department visits were 186 and 19 respectively. The numbers of patients hospitalized due to asthma exacerbation were 43 (61.4%) and 16 (22.9%), and the numbers of total hospitalizations were 124 and 24, respectively. The rate of severe exacerbation, emergency department visit and hospitalization were significantly reduced two years after the treatment by 71.9%, 88.9% and 83.3% (all P<0.001). The scores of ACT and mini-AQLQ were significantly increased [22 (21, 24) vs 17 (13, 19), (5.57±0.89) vs (3.83±0.92); bothP<0.001]. Two years after BT, 4 patients (5.7%) were weaned off inhaled corticosteroids (ICS) and long-acting β₂-agonist (LABA), while 14 patients (37.8%) were weaned off oral corticosteroid (OCS), with daily dose of ICS and OCS significantly decreased (both P<0.05). The proportion of patients treated with montelukast sodium and theophylline was also significantly reduced after BT (40.0% vs 81.4%, 27.1% vs 71.4%; bothP<0.001). In addition, the indicator of FEV₁, FEV₁%pred and FEV₁/FVC ratio were all greatly improved two years after the treatment [2.27 (1.84, 2.82) vs 2.10 (1.70, 2.61) L, (76.8±19.5)% vs (72.5±19.8)%, (66.3±13.6)% vs (63.8±13.0)%; all P<0.05]. The annual cost for asthma drug and asthma treatment after BT were significantly decreased (P<0.001). Fifty-nine patients (84.3%) subjectively assessed the treatment as effective.

The bronchial thermoplasty in "real-world" patients with severe asthma could significantly improve the asthma control, lung function and quality of life, and reduce severe exacerbations, emergency department visits and hospitalizations for asthma symptoms, while the maintenance asthma medications, the cost of asthma drugs and the total annual cost of asthma treatment are significantly decreased.

To analyze the clinicopathological features of clear cell tumor of the lung (CCTL).

A total of 9 cases were collected from August 2008 to August 2019 in the Department of Pathology of the First Medical Center of PLA General Hospital and Hainan Hospital of PLA General Hospital. Their clinical data, pathological characteristics, immunohistochemical staining and special staining results were summarized and analyzed.

There were 3 males and 6 females, aged from 28 to 70 years (average 52.2 years). All tumors were located in the peripheral part of the lung, and were solitary in 8 cases, and multiple (24 nodules) in 1 case. The lesion was round or oval, with clear boundary. The diameter of the nodule was 0.5-5.5 cm. Histologically, the tumor cells were oval, short fusiform or polygonal, with obvious nucleoli. The tumor cells were mostly distributed in sheet around thin-walled vessels, and there was hyaline degeneration around the blood vessels. Neither necrosis nor mitosis could be seen. Immunohistochemical staining showed tumor cells were diffusely positive for Vimentin, and CD34, Melan-A, specific monoclonal antibody against melanoma (HMB45) and S-100 were positive with different degrees. Broad spectrum cytokeratin (CK), epithelial membrane antigen (EMA), smooth muscle actin (SMA), desmin, CD10, paired box gene 8 (PAX-8) or myomodulatory protein (Myo-D1) were all negative. The positive index of the proliferating cell nuclear antigen (Ki-67) was low. Schiff dyeing with periodate (PAS) staining was positive, PAS staining of glycogen digested by amylase (d-PAS) staining was negative. All the tumors in the nine cases were resected and patients were followed up for 5-137 months. Except 1 case was lost for follow-up, the other 8 cases survived without recurrence or metastasis of the disease.

CCTL is a rare benign tumor, most of which are single, few of which can be multiple; histopathological characteristics and immunohistochemical staining are helpful for diagnosis and differentiated diagnosis. After complete resection, the prognosis was good. However, when histological features indicating malignancy, intense follow-up should be considered.

To summarize the clinical characteristics, treatment and prognosis of patients with right intravenous-cardiac leiomyomatosis, and provide references for clinical diagnosis and management.

The clinical data of 22 patients who were admitted to Department of Cardiac Surgery in Beijing Anzhen Hospital from November 2009 to July 2019 were retrospectively reviewed. The long-term prognosis of the patients was also evaluated.

All patients were women, with an age of (48.1±6.3) years. The clinical manifestations of patients lacked specificity. Among them, 14 patients had a history of uterine leiomyoma, 12 had hysterectomy, and 5 had abortions. Twenty patients underwent tumor resection. One-stage operation was performed in 15 cases, while staging surgery was performed in 5 cases. Ten cases underwent tumor resection under cardiopulmonary bypass. One case underwent a tricuspid valve annuloplasty at the same time. There was no death early in postoperative period. Early complications included deep venous thrombosis (2 cases), type Ⅱ atrioventricular block (1 case), pleural effusion (1 case) and incision infection (1 case). In the long-term follow-up (3 years), one case died of tumor recurrence-associated circulatory failure. Among the rest of the patients, the quality of life was satisfying, and cardiac function was between grade Ⅰ and Ⅱ, with no recurrence or metastasis.

Patients with intravenous-cardiac leiomyomatosis are lack of specific manifestations. Early diagnosis is crucial for the treatment of this disease. Tumor resection is an effective treatment, which can improve the quality of life and long-term survival of patients.

To investigate the expression and clinical significance of LRFN4 in colorectal cancer.

A total of 210 cases of colorectal cancer tissues and 228 cases of corresponding surgical margin tissues were collected. Immunohistochemistry was employed to evaluate the expression of LRFN4 in colorectal cancer.The correlation between LRFN4 expression and clinicopathological features of colorectal cancer as well as patient outcome were analyzed.

The positive rate of LRFN4 in colorectal cancer and in non-cancer was 55.24%(116/210), and 37.28% (85/228) , respectively.The expression of LRFN4 in colorectal cancer tissues was higher than that in non-cancer tissues(χ²=14.196, P<0.001). High expression of LRFN4 was significantly correlated with tumor location(χ²=4.133,P=0.042), T staging(χ²=6.494,P=0.039), N staging(χ²=11.715,P=0.008), TNM staging(χ²=13.398,P=0.004), CEA (χ²=6.017, P=0.049), but without gender, age, degree of differentiation, M staging(P>0.05).The Kaplan-Meier survival curves indicated that high LRFN4 expression was associated with good survival (P<0.05). In addition, Cox proportional hazards model showed that the high expression of LRFN4(HR=0.585, P=0.018)was an independent risk factor for prognosis in patients with colorectal cancer.

The expression of LRFN4 is up-regulated in colorectal cancer, which is significantly correlated with the clinicopathological features and prognosis. High expression of LRFN4 reduced the risk of death in patients with colorectal cancer.

To investigate the effect and mechanism of exosome-derived miR-223 from macrophage on gastric cancer (GC) cell metastasis.

Exosomes isolated from macrophages culture medium were characterized and cocultured with GC cell, the miRNA level was detected by qRT-PCR. The migration and invasion of GC cell were detected by transwell. The internalization of exosomes, transfer of miR-223 was observed by immunofluorescence. Macrophage were transfected with a miR-223 inhibitor or negative control, transwell and scratch test were employed to explore the effect of macrophage derived exosome on the migration and invasion of GC cell. Western blot and RT-PCR assay were performed to uncover the underlying mechanisms of miR-223 and PTEN-PI3K/AKT pathway.

This study showed that macrophage and macrophage-derived exosomes promoted the migration and invasion of gastric cancer cell(253.2±6.3, 451.8±12.8, 453.4±14.4, all P<0.01, and 98.4±5.1, 276.5±10.3, 257.3±8.5, allP<0.01, respectively). miR-223 was enriched in macrophage-derived exosomes, which was transferred to the co-cultivated gastric cancer cells. miR-223 knockdown in macrophage reversed the migration and invasion of exosomes on gastric cancer cells(215.6±9.2, 402.5±11.6, 253.7±10.4, allP<0.01, and 91.5±8.2,263.4±9.3,105.8±9.3,allP<0.01, respectively).Functional studies revealed that exosomal miR-223 derived from macrophage promoted the metastasis of GC cells via the PTEN-PI3K/AKT pathway. In addition, itshowed thatthe actin cytoskeleton was altered, and multiple proteins associated with epithelial-mesenchymaltransition (EMT) were upregulated.

Exosomal transfer of macrophage-derived miR-223 promote the metastasis of GC cells through targeting the PTEN-PI3K/AKT pathway.