[Safety of patients undergoing radical resection combined with paclitaxel-based hyperthermic intraperitoneal chemotherapy for locally advanced gastric cancer].

Objective: To analyze the safety of paclitaxel-based, hyperthermic, intraperitoneal perfusion chemotherapy (HIPEC) after radical resection of locally advanced gastric cancer. Methods: This was a retrospective cohort study of clinicopathological data of 467 patients with locally advanced gastric adenocarcinoma who had been admitted to the Department of Gastrointestinal Surgery, West China Hospital, Sichuan University between July 2019 and April 2021. Among these patients, 151 had undergone radical resection combined with post-operative paclitaxel-based HIPEC (surgery+HIPEC group) and 316 radical resection alone (surgery group). The adverse perioperative events in study patients were evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE 5.0) published by the U.S. Department of Health and Human Services. Subgroup analysis was performed on patients in the surgery+HIPEC group according to the number of times HIPEC was administered and the incidence of adverse events was compared between subgroups using the χ2 test. Independent risk factors for paclitaxel-based HIPEC-associated adverse events were identified by applying a logistic model. Results: In the surgery+HIPEC group, there were 113 (74.8%) male and 38 (25.2%) female patients of median age 64 (55, 68) years, 18 (11.9%), 79 (52.3%), and 54 (35.8%) of whom had undergone one, two, and three paclitaxel-based HIPEC treatments, respectively, after surgery. The median maximum tumor diameter was 5.0 (3.6, 6.5) cm. In the surgery group, there were 244 (77.2%) male and 72 (22.8%) female patients of median age 63 (54, 68) and the median maximum tumor diameter was 4.0 (3.0, 5.5) cm. In the surgery+HIPEC group, 112 patients (74.2%) had 198 Grade 2 or higher adverse perioperative events, postoperative hypoalbuminemia being the commonest (85 cases, 56.3%), followed by postoperative anemia (50 cases, 33.1%). Compared with the surgery group, the incidences of postoperative hypoalbuminemia (56.3% [85/151] vs. 37.7% [119/316], χ2=14.420, P<0.001), anemia (33.1% [50/151] vs. 22.5% [71/316], χ2=6.030, P=0.014), abdominal pain [7.3% [11/151] vs. 1.6% [5/316], χ2=10.042, P=0.002) and abdominal distension (5.3% [8/151] vs. 1.3% [4/316], χ2=5.123, P=0.024) were all significantly higher in the surgery+HIPEC group. Analysis of the three HIPEC subgroups revealed significant differences in the incidences of postoperative hypoalbuminemia (13/18 vs. 67.1% [53/79] vs. 35.2% [19/54], χ2=12.955, P<0.001) and pulmonary infection (6/18 vs. 6.3% [5/79] vs. 1.9% [1/54], χ2=13.232, P<0.001) between them. Univariate analysis identified body mass index, Borrmann's type and number of HIPEC treatments as associated with perioperative adverse events in the surgery+HIPEC group (P<0.05). However, according to multifactorial logistic analysis, the above factors were not independent risk factors for perioperative adverse events in the surgery+HIPEC group (P>0.05). Conclusions: Paclitaxel-based HIPEC after radical resection significantly increases the risk of postoperative hypoalbuminemia, anemia, abdominal pain, and abdominal distension in patients who have undergone excision of locally advanced gastric cancer. However, increasing the frequency of HIPEC treatments did not significantly increase the risk of paclitaxel-based HIPEC-related adverse events. Moreover, univariate and multivariate analysis did not identify any independent risk factors for paclitaxel HIPEC-related adverse events.

[Clinicopathological characteristics and prognosis of patients with small bowel tumors: A single center analysis of 220 cases].

Objective: To analyze the clinicopathological characteristics and prognosis of patients with small bowel tumors. Methods: This was a retrospective, observational study. We collected clinicopathological data of patients with primary jejunal or ileal tumors who had undergone small bowel resection in the Department of Gastrointestinal Surgery, West China Hospital, Sichuan University between January 2012 and September 2017. The inclusion criteria included: (1) older than 18 years; (2) had undergone small bowel resection; (3) primary location at jejunum or ileum; (4) postoperative pathological examination confirmed malignancy or malignant potential; and (5) complete clinicopathological and follow-up data. Patients with a history of previous or other concomitant malignancies and those who had undergone exploratory laparotomy with biopsy but no resection were excluded. The clinicopathological characteristics and prognoses of included patients were analyzed. Results: The study cohort comprised 220 patients with small bowel tumors, 136 of which were classified as gastrointestinal stromal tumors (GISTs), 47 as adenocarcinomas, and 35 as lymphomas. The median follow-up for all patient was 81.0 months (75.9-86.1). GISTs frequently manifested as gastrointestinal bleeding (61.0%, 83/136) and abdominal pain (38.2%, 52/136). In the patients with GISTs, the rates of lymph node and distant metastasis were 0.7% (1/136) and 11.8% (16/136), respectively. The median follow-up time was 81.0 (75.9-86.1) months. The 3-year overall survival (OS) rate was 96.3%. Multivariate Cox regression-analysis results showed that distant metastasis was the only factor associated with OS of patients with GISTs (HR=23.639, 95% CI: 4.564-122.430, P<0.001). The main clinical manifestations of small bowel adenocarcinoma were abdominal pain (85.1%, 40/47), constipation/diarrhea (61.7%, 29/47), and weight loss (61.7%, 29/47). Rates of lymph node and distant metastasis in patients with small bowel adenocarcinoma were 53.2% (25/47) and 23.4% (11/47), respectively. The 3-year OS rate of patients with small bowel adenocarcinoma was 44.7%. Multivariate Cox regression-analysis results showed that distant metastasis (HR=4.018, 95%CI: 2.108-10.331, P<0.001) and adjuvant chemotherapy (HR=0.291, 95% CI: 0.140-0.609, P=0.001) were independently associated with OS of patients with small bowel adenocarcinoma. Small bowel lymphoma frequently manifested as abdominal pain (68.6%, 24/35) and constipation/diarrhea (31.4%, 11/35); 77.1% (27/35) of small bowel lymphomas were of B-cell origin. The 3-year OS rate of patients with small bowel lymphomas was 60.0%. T/NK cell lymphomas (HR= 6.598, 95% CI: 2.172-20.041, P<0.001) and adjuvant chemotherapy (HR=0.119, 95% CI: 0.015-0.925, P=0.042) were independently associated with OS of patients with small bowel lymphoma. Small bowel GISTs have a better prognosis than small intestinal adenocarcinomas (P<0.001) or lymphomas (P<0.001), and small bowel lymphomas have a better prognosis than small bowel adenocarcinomas (P=0.035). Conclusions: The clinical manifestations of small intestinal tumor are non-specific. Small bowel GISTs are relatively indolent and have a good prognosis, whereas adenocarcinomas and lymphomas (especially T/NK-cell lymphomas) are highly malignant and have a poor prognosis. Adjuvant chemotherapy would likely improve the prognosis of patients with small bowel adenocarcinomas or lymphomas.

Comparing the efficacy of povidone-iodine and normal saline in incisional wound irrigation to prevent superficial surgical site infection: a randomized clinical trial in gastric surgery.

BACKGROUND: Prevention of surgical site infection (SSI) after gastrectomy has received increasing attention. Prophylactic incisional wound irrigation has been advocated to reduce SSI, but the choice of solution remains under debate. AIMS: To compare the efficacies of wound irrigation with normal saline (NS) and povidone-iodine (PVI) for the prevention of SSI after gastrectomy, and to identify the risk factors for SSI. METHODS: This randomized, single-centre clinical trial included 340 patients with gastric cancer. They were assigned at random into two groups (ratio 1:1) to receive either 0.9% NS or 1.0% PVI solution for incisional irrigation before wound closure. The primary endpoint was postoperative SSI within 30 days of gastrectomy, and the secondary endpoint was the length of hospital stay. FINDINGS: In total, 333 patients were included in the modified intent-to-treat group, and the SSI rate did not differ significantly between the PVI group (11/167, 6.59%) and the NS group (9/166, 5.42%) [odds ratio (OR) 1.131, 95% confidence interval (CI) 0.459-3.712; P=0.655]. Moreover, the difference between the two groups in terms of length of hospital stay was not significant (P=0.301). Body mass index (BMI) (OR 2.639, 95% CI 1.040-6.694; P=0.041) and postoperative complications (OR 2.565, 95% CI 1.023-6.431; P=0.045) were identified as independent risk factors for SSI. CONCLUSIONS: NS and PVI had similar efficacy as prophylactic wound irrigation for the prevention of SSI after gastrectomy. The risk of SSI was higher in patients with high BMI or postoperative complications.

[The impact of the dosage of intraoperative opioids on postoperative survival outcomes in patients with pancreatic cancer].

Objective: To investigate the impact of the dosage of intraoperative opioids on postoperative survival of pancreatic cancer patients who underwent pancreatectomy. Methods: The clinical data of 95 patients with pancreatic cancer who underwent pancreatectomy at Harbin Medical University Cancer Hospital from September 2013 to August 2018 were retrospectively collected. Dosage of intraoperative opioid medications was converted to fentanyl equivalent dose. Patients were divided into high-dose group (fentanyl consumption ≥2.21 mg, n=46) and low-dose group (fentanyl consumption<2.21 mg, n=49) according to the median intra-operative fentanyl equivalents. The relapse-free survival (RFS) and overall survival (OS) between the two groups were compared. Cox proportional hazards regression model was used to analyze the impact of important covariates on RFS and OS. Results: RFS of patients in low-dose group at 1, 3 and 5 years was 75.5%, 26.5% and 15.2% respectively. OS of patients in low-dose group at 1, 3 and 5 years was 77.6%, 32.5% and 24.4% respectively. RFS of patients in high-dose group at 1, 3 and 5 years was 76.1%, 23.9% and 12.0% respectively. OS of patients in high-dose group at 1, 3 and 5 years was 76.1%, 37.0% and 15.0%. There was no significant difference in RFS and OS between the two groups (all P>0.05). Multivariate Cox analysis showed that dosage of intraoperative fentanyl was not associated with RFS (HR=1.205, 95%CI: 0.737-1.970, P=0.456) or OS (HR=1.062, 95%CI: 0.634-1.778, P=0.818). Conclusion: Dosage of intraoperative opioid has no effect on RFS and OS in pancreatic cancer patients undergoing pancreatectomy.

[Safety and effectiveness of esophagojejunostomy through extracorporeal versus intracorporeal methods after laparoscopic total gastrectomy].

Objective: To compare the safety and effectiveness of esophagojejunostomy (EJS) through extracorporeal and intracorporeal methods after laparoscopic total gastrectomy (LTG). Methods: A retrospective cohort study was carried out. Clinicopathological data of 261 gastric cancer patients who underwent LTG, D2 lymphadenectomy, and Roux-en-Y EJS with complete postoperative 6-month follow-up data at the General Surgery Department of Nanfang Hospital from October 2018 to June 2021 were collected. Among these 261 patients, 139 underwent EJS with a circular stapler via mini-laparotomy (extracorporeal group), while 122 underwent intracorporeal EJS (intracorporeal group), including 43 with OrVil(TM) anastomosis (OrVil(TM) subgroup) and 79 with Overlap anastomosis (Overlap subgroup). Compared with the extracorporeal group, the intracorporeal group had higher body mass index, smaller tumor size, earlier T stage and M stage (all P<0.05). Compared with the Overlap subgroup, the Orvil(TM) subgroup had higher proportions of upper gastrointestinal obstruction and esophagus involvement, and more advanced T stage (all P<0.05). No other significant differences in the baseline data were found (all P>0.05). The primary outcome was complications at postoperative 6-month. The secondary outcomes were operative status, intraoperative complication and postoperative recovery. Continuous variables with a skewed distribution are expressed as the median (interquartile range), and were compared using Mann-Whitney U test. Categorical variables are expressed as the number and percentage and were compared with the Pearson chi-square, continuity correction or Fisher's exact test. Results: Compared with the extracorporeal group, the intracorporeal group had smaller incision [5.0 (1.0) cm vs. 8.0 (1.0) cm, Z=-10.931, P=0.001], lower rate of combined organ resection [0.8% (1/122) vs. 7.9% (11/139), χ(2)=7.454, P=0.006] and higher rate of R0 resection [94.3% (115/122) vs. 84.9 (118/139), χ(2)=5.957, P=0.015]. The morbidity of intraoperative complication in the extracorporeal group and intracorporeal group was 2.9% (4/139) and 4.1% (5/122), respectively (χ(2)=0.040, P=0.842). In terms of postoperative recovery, the extracorporeal group had shorter time to liquid diet [(5.1±2.4) days vs. (5.9±3.6) days, t=-2.268, P=0.024] and soft diet [(7.3±3.7) days vs. (8.8±6.5) days, t=-2.227, P=0.027], and shorter postoperative hospital stay [(10.5±5.1) days vs. (12.2±7.7) days, t=-2.108, P=0.036]. The morbidity of postoperative complication within 6 months in the extracorporeal group and intracorporeal group was 25.9% (36/139) and 31.1%, (38/122) respectively (P=0.348). Furthermore, there was also no significant difference in the morbidity of postoperative EJS complications [extracorporeal group vs. intracorporeal group: 5.0% (7/139) vs. 82.% (10/122), P=0.302]. The severity of postoperative complications between the two groups was not statistically significant (P=0.289). In the intracorporeal group, the Orvil(TM) subgroup had more estimated blood loss [100.0 (100.0) ml vs.50.0 (50.0) ml, Z=-2.992, P=0.003] and larger incision [6.0 (1.0) cm vs. 5.0 (1.0) cm, Z=-3.428, P=0.001] than the Overlap subgroup, seemed to have higher morbidity of intraoperative complication [7.0% (3/43) vs. 2.5% (2/79),P=0.480] and postoperative complications [37.2% (16/43) vs. 27.8% (22/79), P=0.286], and more severe classification of complication (P=0.289). Conclusions: The intracorporeal EJS after LTG has similar safety to extracorporeal EJS. As for intracorporeal EJS, the Overlap method is safer and has more potential advantages than Orvil(TM) method, and is worthy of further exploration and optimization.

[Clinical significance of No.11p posterior lymph nodes dissection in gastric cancer surgery].

Objective: To analyze the association of No.11p posterior lymph node metastasis with clinicopathological features and its prognostic significance in gastric cancer. Methods: A single-center retrospective cohort study was conducted. Clinicopathological data of patients with primary gastric cancers undergoing No.11p posterior lymph node dissection from January 2016 to December 2020 were retrieved from the Database of Gastric Cancer, West China Hospital, Sichuan University. Case inclusion criteria: (1) gastric cancer proved by pathology; (2) radical resection with intraoperative No.11p posterior lymph node dissection; (3) operations performed by the same surgical team; (4) no previous history of other malignant tumors and no concurrent malignant tumors. Those with stump gastric cancer, history of gastrectomy, neoadjuvant chemotherapy, incomplete clinicopathological data and lost to follow-up were excluded. During the operation, the upper edge of the pancreas was retracted forward to expose the area between the upper edge of the pancreas and the splenic vessels. The proximal segment of the splenic artery was skeletonized to remove lymphatic tissue anterior and superior to the splenic artery for No.11p lymph node dissection. For patients with lymphadenopathy in the area between the splenic artery and the splenic vein, dissection was performed. The enlarged lymph nodes were labeled with titanium clips and named as No.11p posterior lymph node. Pathological examination was performed separately after the specimen was isolated. Statistical analysis was performed using R software. Results: A total of 127 gastric cancer patients, who underwent No.11p posterior lymph nodes dissection were included in this study, of which 120 patients without No.11p posterior lymph nodes metastasis (No.11p posterior lymph nodes negative) and 7 patients with No.11p posterior lymph nodes metastasis (No.11p posterior lymph nodes positive). A total of 8 metastatic No.11p posterior lymph nodes were detected in 7 patients, metastasis rate and with a ratio of 5.5% (7/127) and 6.8% (8/127), respectively. In the subgroup analysis of T3-4 stage patients, the metastasis rate and ratio of No.11p posterior lymph nodes were 9.0% (7/78) and 10.7% (8/75), respectively. Compared to negative cases, patients with No.11p posterior lymph nodes metastasis had larger tumor (P=0.002), higher proportion of Borrmann type Ⅲ and Ⅳ tumors (P=0.005), more metastatic lymph nodes (P<0.001), more advanced T stage (P=0.043), N stage (P=0.004) and TNM stage (P=0.015). In survival analysis, patients with No.11p posterior lymph node metastasis had a significantly worse prognosis than those without metastasis after adjusting for TNM stage (hazard ratio=3.009, 95% confidence interval: 1.824-4.964, P<0.001). Conclusions: The No.11p posterior lymph node metastasis in gastric cancer is associated with worse prognosis. For patients of T3-4 stage gastric cancer, No.11p posterior lymph node dissection should be emphasized during radical operation.

[Application and clinical significance of TCGA molecular classification in endometrial cancer].

Objective: To explore the application and clinical significance of the cancer genome atlas (TCGA) molecular classification in endometrial cancer (EC). Methods: Sixty-six EC patients collected from December 2018 to March 2021 from Peking University People's Hospital were categorized into four subgroups based on TCGA molecular classification tested by next generation sequencing. The correlation among four molecular subgroups and the clinical-pathological features including prognosis were analyzed. Results: (1) Clinical and pathological features: median age at diagnosis was 56 years (range: 24-78 years). The cases were distributed as follows: 3 (5%) cases DNA polymerase epsilon (POLE) ultra-mutated, 11 (17%) cases high microsatellite instability (MSI-H) including 2 Lynch syndrome, 42 (64%) cases low copy-number (CN-L) and 10 (15%) cases high copy-number (CN-H). There were significant differences among four subtypes in the combination of other tumors, tumor family history, surgical method, International Federation of Gynecology and Obstetrics (FIGO, 2009) stage, depth of muscle invasion and lymph vascular space invasion (all P<0.05). The proportions of patients in CN-H subgroup with advanced FIGO stage (stage Ⅲ-Ⅳ), deep muscle invasion and positive lymph-vascular space invasion were significantly increased. There were no significant differences in age, menopausal status, body mass index, metabolic syndrome-related complications, preoperative serum CA125 and human epididymis protein 4 levels, tumor size, pathological grade (only endometrioid cancer), and lymph node metastasis among the 4 TCGA molecular types (all P>0.05). (2) Immuno-related molecular analysis: among 66 EC patients, 27 patients underwent immunohistochemical analysis of programmed cell death 1 ligand 1 (PD-L1) protein, and 28 patients underwent tumor mutation burden (TMB) detection. POLE and MSI-H subgroups contained TMB than those in CN-L and CN-H (P<0.05).(3) Prognosis: the median follow-up time was 10 months (range: 0-28 months). The progression-free survival rate of TCGA molecular types were 100% (POLE ultra-mutated), 100% (MSI-H), 98% (CN-L), and 80% (CN-H) respectively and had significant differences (P=0.034). The overall survival were 100% (POLE ultra-mutated), 100% (MSI-H), 98% (CN-L), and 90% (CN-H) respectively, but there were not statistically significant difference (P=0.361). POLE ultra-mutated and MSI-H subgroups had the best survival, while CN-H had the worst. Conclusion: TCGA molecular classification has feasibility and clinical value in clinical application of EC, which is helpful to identify the prognosis of patients.

[The treatment strategy and outcome of pregnancy complicated with Stanford type A aortic dissection].

To summarize the clinical characteristics and surgical treatment experience of pregnant women with acute Stanford type A aortic dissection.We collected the clinical data of 12 cases with acute aortic dissection during pregnancy and puerperal period from June 2010 to July 2020 in Beijing Anzhen Hospital and analyzed retrospectively, and summarize the clinical characteristics, treatment and outcomes for both mother and fetus. The age of these patients was(29±5)years old, and the onset time was from 16 weeks of gestation and 1 month after delivery. All the 12 patients underwent surgical treatment. The patients in the puerperium received aortic surgery after delivery. Four of them received the aortic surgery and continued pregnancy. Five of them underwent aortic repair and cesarean section simultaneously. Surgical treatment should be actively considered in pregnancy complicated with acute Stanford type A aortic dissection. Multi-disciplinary team cooperation can effectively improve the safety of the patients and fetus.

[The value of synthetic MRI in differential diagnosis of benign and malignant breast lesions].

Objective: To explore the diagnostic value of synthetic magnetic resonance imaging (syMRI) quantitative parameters for benign and malignant breast lesions. Methods: From September 2018 to March 2019, a total of 43 cases of breast lesions which were confirmed by surgery and pathology in Cancer Hospital, Chinese Academy of Medical Sciences were enrolled in this study. All patients underwent syMRI sequence scans before and after enhancement except for conventional T2WI, DWI, and enhancement scans. GE AW4.7 workstation was used to generate syMRI parameter maps (T1, T2, proton density mappings), and ITK-SNAP software was used to delineate the volume of interest. The T1, T2, PD values before and after dynamic contrast enhanced (DCE) were obtained, and the change values of each parameter were calculated. Meanwhile, the apparent diffusion coefficient (ADC) and time intensity curve (TIC) of the lesions were measured. The differences of each parameter value were compared between benign and malignant breast lesions, and the receiver operating characteristic (ROC) curve was used to analyze the diagnostic performance of each parameter. Results: Among the 43 enrolled cases, 13 were benign and 30 were malignant. Among the syMRI parameters, the pre-enhancement parameters including T1pre (median 1 663.07 ms), T2pre (median 103.33 ms), post-enhancement parameters ΔT1 (median 1 022.68 ms) and ΔT2 (median 27.67 ms) of benign group, significantly higher than those of the malignant group (the medians were 1 141.74, 92.53, 664.95, and 16.19 ms, respectively, P<0.05). The ADC value of the benign group (median 1.66×10(-3)mm(2)/s) was significantly higher than that of the malignant group (median 1.00×10(-3)mm(2)/s, P<0.05). The benign group included 6 cases of TIC curve type Ⅰ, 5 cases of type Ⅱ, and 2 cases of type Ⅲ. The malignant group included 2 cases of TIC curve type Ⅰ, 17 cases of type Ⅱ, and 11 cases of type Ⅲ. The difference between the two groups was statistically significant (P<0.05). The area under the ROC curve (AUC) of T1pre before DCE was 0.869, higher than 0.806 of ADC and 0.697 of TIC. When the best cut-off value of 1 282.94 ms was chosen, the sensitivity and specificity of diagnosis were 76.9% and 93.3%, respectively. The combination of T1pre and T2pre can further improve the diagnostic performance (AUC=0.908). Conclusions: Among the syMRI quantitative parameters, T1pre, T2pre, ΔT1 and ΔT2 have good value for the differential diagnosis of benign and malignant breast lesions. T1pre has the best diagnostic performance, and the combination of T1pre and T2pre can further improve the diagnostic performance.

Comparison of clinical features and outcomes for asthma-COPD overlap syndrome vs. COPD patients: a systematic review and meta-analysis.

OBJECTIVE: The aim of this study was to review evidence to determine whether "pure" chronic obstructive pulmonary disease (COPD) patients without a history of asthma differ in the clinical characteristics, severity of airflow limitation, and clinical outcomes compared to patients with Asthma-COPD Overlap Syndrome (ACOS). MATERIALS AND METHODS: An electronic search was performed in the MEDLINE, EMBASE, SCOPUS and Web of Science databases to identify comparing the clinical characteristics and outcomes between ACOS and "pure" COPD. The included studies were subjected to meta-analysis and risk of bias assessment using ROBINS-E tool. Eleven observational studies were included. RESULTS: The results of the meta-analysis showed increased expression of lung function parameters like forced expiration volume (FEV) at 1 sec{mean difference (MD) 2.36; 95% CI [0.05,4.66] ; p=0.004; I2= 72%} and clinical symptoms in terms of fever {Relative Risk (RR) 0.34, p<0.0001}, wheezing {RR 0.39, p<0.0001} and dyspnea {RR 0.53, p<0.0001}. The comorbidities associated with ACOS patients were similar to that found in patients with "pure" COPD. Interestingly, higher body mass index (BMI) was found in patients with ACOS (MD -0.73 95% CI [-1.06, -0.41], p<0.0001. CONCLUSIONS: The result showed higher risk in onset of frequent acute exacerbations, severe exacerbations requiring hospitalization and higher number of exacerbations experienced per year in ACOS patients. Within the limitations of the review, ACOS can be regarded as separate entity of co-existence which is classically associated with higher BMI, worsened lung function parameters and exacerbations with a varying degree of clinical symptoms.

[Novel compound heterozygous LoF mutations in SRD5A2 may result in disorders of sex development].

Objective: To investigate the novel genetic cause associated with hypospadias and the strategy for preventing offspring genetic defects in these patients. Methods: 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. Results: 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 (E(2)), 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 concentration<2×10(6)/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. Conclusion: 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.

Epidemiological characteristics of COVID-19 patients in convalescence period.

This study aimed to investigate the clinical characteristics and to analyse the epidemiological features of coronavirus disease 2019 (COVID-19) patients during convalescence. In this study, we enrolled 71 confirmed cases of COVID-19 who were discharged from hospital and transferred to isolation wards from 6 February to 26 March 2020. They were all employees of Zhongnan Hospital of Wuhan University or their family members of which three cases were <18 years of age. Clinical data were collected and analysed statistically. Forty-one cases (41/71, 57.7%) comprised medical faculty, young and middle-aged patients (aged ⩽60 years) accounted for 81.7% (58/71). The average isolation time period for all adult patients was 13.8 ± 6.1 days. During convalescence, RNA detection results of 35.2% patients (25/71) turned from negative to positive. The longest RNA reversed phase time was 7 days. In all, 52.9% of adult patients (36/68) had no obvious clinical symptoms, and the remaining ones had mild and non-specific clinical symptoms (e.g. cough, sputum, sore throat, disorders of the gastrointestinal tract etc.). Chest CT signs in 89.7% of adult patients (61/68) gradually improved, and in the others, the lesions were eventually absorbed and improved after short-term repeated progression. The main chest CT manifestations of adult patients were normal, GGO or fibre streak shadow, and six patients (8.8%) had extrapulmonary manifestations, but there was no significant correlation with RNA detection results (r = -0.008, P > 0.05). The drug treatment was mainly symptomatic support therapy, and antibiotics and antiviral drugs were ineffective. It is necessary to re-evaluate the isolation time and standard to terminate isolation for discharged COVID-19 patients.

[Management strategy for the resumption of regular diagnosis and treatment in gastrointestinal surgery department during the outbreak of coronavirus disease 2019 (COVID-19)].

Acute abdomen, abdominal trauma, gastrointestinal bleeding and gastrointestinal tumors are the main conditions that are routinely treated in gastrointestinal surgery department with high incidence and critical condition. These conditions need emergency or selective operations. During the outbreak of the coronavirus disease 2019 (COVID-19), it's a great challenge for us to meet the patients' requirement under the situation. As the COVID-19 was brought under control in China, the Department of General Surgery in Nanfang Hospital resumed regular medical services gradually. Based on our clinical practice, the four major measures of strengthening pre-hospital screening, perioperative prevention and control, medical staff protection, and ward management were adopted. These main measures include the strict implementation of the appointment system and triage system before admission; the conduction of epidemiological and preliminary screening of viral nucleic acids; the chest CT examination during the perioperative period to re-screen COVID-19; the reduction of the risk of droplets and aerosol transmission; the minimally invasive surgery combined with enhanced recovery program in order to reduce patient's susceptibility and shorten the length of postoperative hospital stay; the reinforcement of specific infection control training for medical staff; the strict implementation of hierarchical protection; the establishment of gastrointestinal surgery prevention and control system; the rehearsal of emergency exercise; the installation of quarantine wards; the screening and management of family care-givers; the strict disinfection of environment and materials. Our preliminary practice shows that following the work guidelines issued by the Guangdong Province COVID-19 Prevention and Control Office and adopting precise management strategies in combination with the specific clinical features of gastrointestinal surgery, it is possible to safely resume regular care for the patients and comply to epidemic control at the same time.

[Effect of standardized surgical treatment and multidisciplinary treatment strategy on the prognosis of gastric cancer patients: report of a single-center cohort study].

Objective: To explore the effect of standardized surgical treatment and multidisciplinary treatment strategy on the treatment outcomes of gastric cancer patients. Methods: A single-center cohort study was carried out. Clinicopathological and long-term follow up data of primary gastric cancer patients were retrieved from the database of Surgical Gastric Cancer Patient Registry (SGCPR) in West China Hospital of Sichuan University. Finally, 4516 gastric cancer patients were included and were divided into three groups according to time periods (period 1 group: exploration stage of standardized surgical treatment, 2000 to 2006, 967 cases; period 2 group: application stage of standardized surgical treatment, 2007 to 2012, 1962 cases; period 3 group: optimization stage of standardized surgical treatment and application stage of multidisciplinary treatment strategy, 2013 to 2016, 1587 cases). Differences in clinical data, pathologic features, and prognosis were compared among 3 period groups. Follow-up information was updated to January 1, 2020. The overall follow-up rate was 88.9% (4016/4516) and median follow-up duration was 51.58 months. Survival curve was drawn by Kaplan-Meire method and compared with log-rank test. Univariate and multivariate analyses were performed by Cox proportional hazards model. Results: There were significant differences among period 1, period 2 and period 3 groups in the rates of D2/D2+ lymphadenectomy [14.4%(139/967) vs. 47.2%(927/1962) vs. 75.4%(1197/1587), χ(2)=907.210, P<0.001], in the ratio of proximal gastrectomy [19.8%(191/967) vs. 16.6%(325/1962) vs. 8.2%(130/1587), χ(2)=100.020, P<0.001], and in the median intraoperative blood loss (300 ml vs. 100 ml vs. 100 ml, H=1126.500, P<0.001). Besides, the increasing trend and significant difference were also observed in the median number of examined lymph nodes among period 1, period 2 and period 3 groups (14 vs. 26 vs. 30, H=987.100, P<0.001). Survival analysis showed that the 5-year overall survival rate was 55.3% in period 1, 55.2% in period 2 and 62.8% in period 3, and significant difference existed between period 3 and period 1 (P=0.004). The Cox proportional hazards model analysis showed that treatment period (period 3, HR=0.820, 95%CI: 0.708 to 0.950, P=0.008), postoperative chemotherapy (HR=0.696, 95%CI: 0.631 to 0.768, P<0.001) and mid-low gastric cancer (HR=0.884, 95%CI: 0.804 to 0.973, P=0.011) were good prognostic factors. Whereas old age (≥65 years, HR=1.189, 95%CI: 1.084 to 1.303, P<0.001), palliative resection (R1/R2, HR=1.538,95%CI: 1.333 to 1.776, P<0.001), large tumor size (≥5 cm, HR=1.377, 95%CI: 1.239 to 1.529, P<0.001), macroscopic type III to IV (HR=1.165, 95%CI: 1.063 to 1.277, P<0.001) and TNM stage II to IV(II/I:HR=1.801,95%CI:1.500~2.162,P<0.001;III/I:HR=3.588, 95%CI: 3.028~4.251, P<0.001; IV/I: HR=6.114, 95%CI: 4.973~7.516, P<0.001) were independent prognostic risk factors. Conclusion: Through the implementation of standardized surgical treatment technology and multidisciplinary treatment model, the quality of surgery treatment and overall survival increase, and prognosis of gastric cancer patients has been improved.

Development and application of isothermal amplification methods for rapid detection of F4 fimbriae producing Escherichia coli.

Enterotoxigenic Escherichia coli (ETEC) is the causative agent of a wide range of diseases, which are the important cause of illness and mortality in piglets. ETEC strains expressing F4 fimbriae are frequently associated with post-weaning diarrhea (PWD) and lead to great economic losses in swine production industry worldwide. The aim of this study was to establish a rapid and effective isothermal amplification method for detection of F4 fimbriae. Loop-mediated isothermal amplification (LAMP), Polymerase spiral reaction (PSR) and cross-priming ampli- fication (CPA) were used to develop and optimize the detection method first time. Subsequently, the specificity and sensitivity of these methods were evaluated, and the clinical samples were detected with these methods. All the F4-positive samples could produce ladder-like amplifica- tions products and lead the chromogenic substrate SYBR Green I produce green fluorescence, while in blank control and negative samples lack of this pattern or remained orange. The sensi- tivity of LAMP and CPA were 10 times higher than PSR method. Meanwhile, these three methods were validated with clinical samples, 7 were found positive, while 125 samples were negative, the testing results were consisted with the real-time PCR method. These findings suggested that the isothermal amplification based on the F4 fimbriae is a rapid, effective and sensitive method under resource constrains.

[Vascular injury and anatomy during laparoscopy - assisted distal gastrectomy with D2 lymphadenectomy for gastric cancer].

Objective: To evaluate the incidence of intraoperative vascular injury (IVI) and associated anatomical features during laparoscopy - assisted distal gastrectomy (LADG) with D2 lymphadenectomy for gastric cancer. Methods: A descriptive cohort study was performed. Clinical data and operational videos of 278 consecutive gastric cancer patients who underwent LADG with D2 lymphadenectomy for gastric cancer at Department of General Surgery of Nanfang Hospital between January 2010 and December 2017 were retrospectively analyzed. IVI and vascular anatomy during lymphadenectomy were observed and recorded in the following four scenes: scene I: No. 4sb and No.4d of lower left (tail of pancreas) area; scene II: No.6 of lower right (subpyloric) area; scene III: No.5 and No.12a of upper right (suprapyloric) area; scene IV: No. 7, No. 8a, No. 9, No. 11p of central area posterior to the gastric body. IVI was defined as the injury of main perigastric vessel requiring additional procedure for hemostasis such as electrocauterization, gauze compression, clipping or suture. Results: Among 278 patients, 125 (45.0%) had IVI. Two cases of IVI required conversion to open operation and the injuried vascular was left gastric artery (LGA) and right gastric artery (RGA), respectively. Higher incidence of IVI was found in scene II (92/278, 33.1%) and scene IV(39/278, 14.0%). More common IVI was observed in right gastroepiploic vein (RGeV, 57/278, 20.5%) and left gastric vein (LGV, 33/278, 11.9%). The right gastroepiploic vessels were observed in all 278 patients, including 3 (1.1%) cases with 2 RGeVs, and 2 cases with 2 right gastroepiploic arteries (RGeA). RGA was observed clearly in 265 (95.3%) patients, whose ramification pattern was as follows: from proper hepatic artery (PHA, 223/265, 84.2%), from gastroduodenal artery (GDA, 16/265, 6.0%), from left hepatic artery (LHA, 12/265,4.5%), from the crossing of PHA and GDA (8/265, 3.0%), and 6 (2.3%) patients with 2 RGAs simultaneously from PHA and GDA, respectively. The most common injury of RGA (4/12) occurred in LHA. Excluding 2 cases of conversion to open surgery due to intraoperative hemorrhage, among 276 patients, LGV was observed in 270 patients (97.1%), whose drainage pattern was as follows: into the portal vein (PV, 148/270, 54.8%), into the spleen vein (SV, 56/270, 20.7%), into the junction of these two veins (52/270, 19.3%), into left portal vein (LPV, 8/270, 3.0%), meanwhile 6 patients had 2 LGVs simultaneously, including LGVs of 5 cases into PV and SV, and of 1 case into PV-SV junction and SV. The most common IVI was found in those patients with two LGVs (4/6). Conclusions: IVI during LADG with D2 lymphadenectomy is common. The highest risk of IVI is found in scene II and scene IV. Attentions should be paid to anatomic variation of vessels, especially the RGeV, LGV and RGA.

LncRNA MEG3 accelerates apoptosis of hypoxic myocardial cells via FoxO1 signaling pathway.

OBJECTIVE: To explore the effects of long non-coding ribonucleic acid (lncRNA) maternally expressed gene 3 (MEG3) on the proliferation and apoptosis of hypoxic myocardial cells by regulating the expression of forkhead box O1 (FoxO1). MATERIALS AND METHODS: The myocardial A10 cell lines were divided into myocardial cell group (group A), hypoxic myocardial cell group (group B), and hypoxic myocardial cell + transfection with lncRNA MEG3 mimic group (group C). The correlations of the adenosine triphosphate (ATP) concentration, the degree of apoptosis, and the proliferation with FoxO1 and FoxO3a proteins in the cells were observed via ATP assay, Cell Counting Kit-8 (CCK-8) assay, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, Western blotting, and quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR), respectively. RESULTS: The ATP concentration in myocardial cells was the highest in group A (p<0.05), and it was higher in group B than that in group C (p<0.05). The results of the CCK-8 assay showed that the proliferation rate of the myocardial cells was the highest in group A and the lowest in group C (p<0.05), and it was significantly increased in group B compared with that in group C (p<0.05). The results of the TUNEL assay revealed that the normal cells displayed the purple color, and apoptotic cells displayed the green color. The myocardial cells were arranged orderly, and the number of apoptotic cells was smaller in group A, the number of apoptotic cells was significantly larger in group B than that in group A, and it was the largest in group C (p<0.05). Moreover, the results of Western blotting manifested that the concentrations of FoxO1 and FoxO3 proteins in myocardial cells were the lowest in group A (p<0.05), and they were significantly higher in group C than those in group B (p<0.05). According to the results of qRT-PCR, the mRNA expressions of FoxO1 and FoxO3 in myocardial cells were the lowest in group A (p<0.05), and they were remarkably lower in group B than those in group C (p<0.05). CONCLUSIONS: LncRNA MEG3 can increase the activity of FoxO1 to promote myocardial apoptosis in a hypoxic environment.

[Clinical treatment experience of thyroid cancer with heart disease].

Objective: To explore the perioperative clinical treatment of thyroid cancer patients with heart disease. Methods: A retrospective analysis was conducted on 39 thyroid cancer patients with heart disease admitted to the Department of Otorhinolaryngology Head and Neck Surgery, Beijing Anzhen Hospital,Capital Medical University from April 2014 to February 2018,including 25 males and 14 females, the age ranged from 59 to 75 years,with an average age of 67.3±6.2 years. Perioperative clinical monitoring indicators included cardiac ultrasound left ventricular ejection fraction (LVEF), degree of vascular stenosis revealed by coronary CT, hypersensitive troponin I (TNI), b-type natriuretic peptide (BNP), fibrinogen degradation products,and coagulation indexes. This panel of patients comprised 26 cases with 50% ≤ LVEF<60%,10 cases with 40% ≤ LVEF<50%, 3 cases with 36% ≤ LVEF<40%, 27 cases with 0≤BNP<100 ng/L, 7 cases with 100≤BNP<400 ng/L, and 5 cases with 400≤BNP<700 ng/L. Coronary CT showed no coronary artery stenosis>75%. The vascular graft was patent and the coronary artery after stenting was unobstructed. For 3 patients with LVEF<40% and 5 patients with BNP>400 ng/L,cardiotonic,diuretic,and nutritional myocardial therapy were used for 1 week. SPSS 17.0 software was used to analyze the data. Results: All 39 patients successfully completed the operation under general anesthesia,including 32 cases of total thyroidectomy,7 cases of glandular lobe and isthmic resection,and 40 cases of lateral neck dissection. One patient developed heart failure three days after surgery and was discharged after two weeks of treatment. No other cardiac related events,cerebrovascular and pulmonary thrombosis occurred during the perioperative period. The anesthesia preparation time was significant different between the group with 0≤BNP<100 ng/L and 50%≤LVEF<60% and the group with 0≤BNP<100 ng/L and 36%≤LVEF<50%. Conclusions: Multi-indicators were utilized to adequately assess cardiac function before surgery. According to the results of cardiac ultrasound and coronary CT examination, the corresponding treatment should be conducted to improve the cardiac function. After the perioperative risk assessment and management of thyroid cancer patients with heart disease,standardized thyroid cancer surgery can be performed safely.

Effect of ulinastatin on myocardial ischemia reperfusion injury through ERK signaling pathway.

OBJECTIVE: To study the effect of ulinastatin (UTI) on myocardial ischemia-reperfusion injury (MIRI) through the extracellular signal-regulated kinase (ERK) signaling pathway. MATERIALS AND METHODS: A total of 24 Sprague-Dawley rats were randomly divided into sham group (n=8), I/R group (n=8), and UTI group (n=8), and the rat model of MIRI was established. The changes in the content of serum biochemical indexes, including superoxide dismutase (SOD) and malondialdehyde (MDA), were detected using the kits, and the changes in the expressions of serum inflammatory factors, including interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), were detected using the quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) kits. Moreover, the ERK phosphorylation level in myocardial tissues was detected using the immunofluorescence method, and the ERK phosphorylation level and cleaved caspase-3 expression were detected via qRT-PCR and Western blotting. RESULTS: Compared with those in sham group, the serum SOD content significantly declined, while the MDA content was significantly increased in I/R group, and they were significantly improved in UTI group (p<0.01). The results of detection using qRT-PCR and ELISA kits revealed that the inflammatory factors (IL-6 and TNF-α) in UTI group were significantly improved (p<0.01). The immunofluorescence results showed that the ERK phosphorylation level in myocardial tissues was significantly increased in UTI group. The results of qRT-PCR and Western blotting manifested that both ERK phosphorylation level and cleaved caspase-3 expression were significantly improved in UTI group (p<0.01). CONCLUSIONS: UTI can play a protective role in MIRI through up-regulating the ERK signaling pathway.

LncRNA LINC00673 inhibits p53 expression by interacting with EZH2 and DNMT1 in papillary thyroid carcinoma.

OBJECTIVE: This study aims to elucidate the regulatory role of long noncoding RNA (lncRNA) LINC00673 in proliferative, invasive and metastatic capacities of papillary thyroid carcinoma (PTC), and to investigate the possible underlying mechanism. PATIENTS AND METHODS: LINC00673 expression in PTC tissues and cell lines was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The correlation between LINC00673 expression and PTC prognosis was analyzed. By plasmid transfection, we constructed PTC cell lines with stable knockdown of LINC00673. The regulatory effect of LINC00673 on the proliferation of K1 and TPC-1 cells were determined by Cell Counting Kit-8 (CCK-8) assay and colony formation assay. The transwell assay was conducted to evaluate the effect of LINC00673 on the metastatic ability of PTC cells. The binding condition between LINC00673 with enhancer of zeste homolog 2 (EZH2) and DNA Methyltransferase 1 (DNMT1) was verified by RNA immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP) and Western blot. The cellular mechanism of p53 in regulating biological behaviors of PTC cells was explored by Western blot. Finally, the gain-of-function experiment was performed to elucidate whether LINC00673 could regulate PTC development by inhibiting p53 expression. RESULTS: LINC00673 expression in PTC tissues was significantly higher than that of the adjacent normal tissues. Besides, higher expression of LINC00673 indicated worse prognosis of PTC. The knockdown of LINC00673 in K1 and TPC-1 cells markedly reduced the proliferative rate. Meanwhile, LINC00673 down-regulation remarkably inhibited the migratory and invasive capacities of K1 and TPC-1 cells. RIP and ChIP assay demonstrated that LINC00673 could bind to EZH2 and DNMT1. Besides, Western blot analysis showed that LINC00673 negatively regulated p53 expression. In addition, the knockdown of p53 in K1 and TPC-1 cells partially reversed the inhibitory effect of LINC00673 deficiency on the proliferation and metastasis of PTC cells. CONCLUSIONS: High expression of LINC00673 in PTC predicts a poor prognosis. LINC00673 remarkably promotes the proliferation and invasion of PTC cells by inhibiting p53 expression by binding to EZH2 and DNMT1.