[Concomitant extragenital malformations of female reproductive tract anomalies: analysis of 444 cases in Peking Union Medical College Hospital].

Objective: To analyze the incidence and clinical phenotype of the concomitant extragenital malformations in the patients with female reproductive tract anomalies. Methods: A retrospective study was conducted using clinical data of hospitalized patients diagnosed with uterine, cervical, or vaginal malformations from January 2003 to December 2022 in Peking Union Medical College Hospital. The malformations were classified according to American Society for Reproductive Medicine müllerian anomalies classification 2021, and in each type, the incidence and specific manifestations of concomitant extragnital malformations were analyzed. Results: A total of 444 patients were included. The overall incidence of concomitant extragenital malformations was 43.5% (193/444), including urinary system, skeletal system, and other system malformations. Renal malformations on the obstructed side were present in all patients with oblique vaginal septum syndrome (100.0%, 78/78). The total incidence of concomitant extragnital malformations was as high as 8/11 in uterus didelphys, 43.5% (10/23) in unicornuate uterus, 33.6% (79/235) in Mayer-Rokitansky-Küster-Hauser syndrome, 18.8% (6/32) in septate uterus and 18.5% (12/65) in cervical agenesis. Urinary system malformations (30.6%, 136/444) and skeletal system malformations (13.5%, 60/444) were the most common concomitant malformations in all types, in which, unilateral renal agenesis and scoliosis were the most common. Conclusions: Urinary and skeletal system malformations are important features of female reproductive tract anomalies. Urologic ultrasonography and spinal roentgenogram are recommended for all patients with female reproductive tract anomalies.

[Association between digestive tract cancer and severity of coronary artery disease].

Objective: To evaluate the association between digestive tract cancer and anatomical severity of coronary artery disease. Methods: This study enrolled 142 patients with digestive tract cancer who underwent coronary angiography in the Department of Cardiology of the First Medical Center of Chinese PLA General Hospital from 2009 to 2020 as the cancer group. The patients in cancer group were matched with 426 non-cancer patients who underwent coronary angiography at our hospital during the same period in a 1∶3 ratio based on gender and age. All enrolled patients had no previous history of percutaneous coronary intervention or coronary artery bypass grafting surgery. The severity of coronary artery disease was documented and assessed using the SYNTAX score based on angiogram. High SYNTAX score (SXhigh) was defined as SYNTAX score≥22 (upper quartile), while low SYNTAX score (SXlow) was SYNTAX score<22. High NLR (NLRhigh) was NLR≥2.287 (median), while low NLR (NLRlow) was NLR<2.287. The association between digestive tract cancer and severity of coronary artery disease was analyzed using logistic regression analysis. Results: This study included a total of 568 patients, with a mean age of (66.6±8.7) years. Among them, 430 patients (75.7%) were male. The cancer group consisted of 142 patients with digestive tract cancers, with a mean age of (66.5±8.4) years. The non-cancer group consisted of 426 patients, with a mean age of (66.7±8.8) years. The proportion of SXhigh in patients with digestive tract cancers (33.1%, 47 patients) was higher than that in non-cancer patients (23.9%, 102 patients) (P=0.032). Compared to non-cancer patients, SXhigh in patients with digestive tract cancers was higher (OR: 1.614, 95%CI: 1.051-2.481, P=0.029). Subgroup analysis stratified by NLR levels revealed that in the NLRhigh group, patients with digestive tract cancers exhibited a higher severity of coronary artery disease compared to non-cancer patients, with an OR of 1.948 (95%CI: 1.005-3.779, P=0.048). In the NLRlow group, there was no significant relationship between digestive tract cancers and the severity of coronary artery disease, with an OR of 1.277 (95%CI: 0.586-2.781, P=0.538). Conclusions: Digestive tract cancer is associated with the severity of coronary artery disease, and patients with digestive tract cancers have a higher risk of severe coronary artery disease than non-cancer patients. Additionally, there is an association between digestive tract cancers and the severity of coronary artery disease under conditions of high levels of inflammation.

[Risk factors and predictors of persistent ectopic pregnancy after interstitial pregnancy surgery].

Objective: To explore the related factors and early predictors of persistent ectopic pregnancy (PEP) in patients with interstitial pregnancy after operation. Methods: The clinical data of patients with interstitial pregnancy who underwent surgery in the Department of Obstetrics and Gynecology of Peking Union Medical College Hospital from January 2013 to August 2021 were collected. Patients were divided into two groups according to whether PEP occurred (8 patients in PEP group and 124 patients in non-PEP group). Using propensity score matching (PSM) analysis, the basic data, surgical methods, the ratio of postoperative to preoperative serum ß-human chorionic gonadotropin (ß-hCG), the duration of when the serum ß-hCG had decreased to normal after the operation were compared and analyzed to find the related factors of PEP after interstitial pregnancy surgery. The sensitivity and specificity of the ratio of 24-48 hours postoperative ß-hCG to preoperative ß-hCG in predicting postoperative PEP were evaluated by drawing receiver operating characteristic (ROC) curve. Results: Before PSM, the ages of patients in PEP group and non-PEP group were (30.0±4.0) and (32.4±5.0) years old, respectively, P>0.05. After PSM, 8 PEP patients in the study group and 29 patients in the control group were matched successfully, and the ages of the two groups were (30.0±4.0) and (30.1±3.2) years old, respectively, P>0.05. After PSM, there was no significant difference in gravidity, parity, menopausal days, preoperative ß-hCG level and maximum diameter of lesions, all P>0.05. After PSM, the proportion of patients with maximum diameter ≤ 2.6 cm in PEP group (6/8) was significantly higher than that in control group (31.0%, 9/29), P=0.025. The median (Q1, Q3) of the ratio of 24-48 hours postoperative ß-hCG to preoperative ß-hCG ratio was 52.9% (49.9%, 59.7%) in the PEP group, which was significantly higher than 31.5% (23.8%, 39.0%) in the control group (P=0.001); The median (Q1, Q3) of duration of when the serum ß-hCG had decreased to normal after the operation in PEP group was 52.0 (34.8, 92.0) d, which was significantly higher than 24.0 (20.5, 31.0) d in control group (P<0.001). The ROC-Area Under Curve of the ratio of 24-48 hours postoperative ß-hCG to preoperative ß-hCG ratio for predicting postoperative PEP in the two groups was 0.892 (95%CI: 0.725-1.000, P=0.001). The cut-off value for predicting PEP was 48.5%, where the diagnostic sensitivity was 87.5%, the specificity was 93.1%. Conclusions: In the operation of interstitial pregnancy, the maximum diameter of lesion ≤ 2.6 cm is a related factor for postoperative PEP. There was no significant difference in the risk of PEP between cornuotomy and cornectomy. The ratio that 24-48 hours postoperative ß-hCG/preoperative ß-hCG ratio greater than 48.5% was a reference index for predicting postoperative PEP and guiding treatment.

Sacrocolpopexy compared with transvaginal mesh surgery: a systematic review and meta-analysis.

BACKGROUND: The use of mesh is controversial in the treatment of female pelvic organ prolapse. OBJECTIVES: To systematically review the outcomes of sacrocolpopexy compared with transvaginal mesh surgery and to provide evidence-based suggestions. SEARCH STRATEGY: The MEDLINE, EMBASE, Cochrane Library and clinicaltrials.gov databases were searched on 21 November 2018. SELECTION CRITERIA: Randomised controlled trials and prospective and retrospective cohort studies were included. DATA COLLECTION AND ANALYSIS: Data were extracted by one reviewer and examined by a second reviewer for accuracy. Odds ratios and 95% CI were calculated using random-effects models. MAIN RESULTS: Twenty comparative studies were included. The meta-analysis was performed with subgroups. The summary odds ratios of the randomised controlled group were 1.84 (95% CI 0.79-4.29, I2  = 75%) for anatomical success, 1.41 (95% CI 0.47-4.24, I2  = 38%) for subjective success, 0.42 (95% CI 0.18-0.98, I2  = 0%) for mesh complications, 0.61 (95% CI 0.20-1.91, I2  = 0%) for prolapse reoperation and 0.44 (95% CI 0.23-0.88, I2  = 0%) for de novo dyspareunia. The mean differences were 0.77 (95% CI 0.31-1.23, I2  = 66%) for total vaginal length and -1.28 (95% CI -2.00 to -0.55, I2  = 66%) for point C after surgery. CONCLUSIONS: Very-low-quality evidence indicated that the anatomical and subjective success rates of sacrocolpopexy were similar to those of transvaginal mesh surgery; sacrocolpopexy might be more beneficial than transvaginal mesh surgery in terms of mesh-related complication rates, prolapse recurrence and de novo dyspareunia. However, additional high-quality randomised trials with long-term follow-up durations are needed. TWEETABLE ABSTRACT: Sacrocolpopexy is beneficial after surgical anatomical changes and has decreased rates of mesh-related complications and dyspareunia.

[The prognostic value of myocardial infarct size measured by cardiovascular magnetic resonance in patients with acute ST-segment elevation myocardial infarction].

Objective: To investigate the prognostic value of infarct size (IS) in patients with acute ST-segment elevation myocardial infarction (STEMI) underwent primary percutaneous coronary intervention (PCI). Methods: A total of 104 patients with acute STEMI who underwent primary PCI treatment in Shengjing Hospital of China Medical University from February 2017 to November 2018 were included in the present study. All patients underwent cardiovascular magnetic resonance (CMR) within one week after primary PCI treatment. The subjects were followed up for two years. Major adverse cardiac events (MACE) included new onset congestive heart failure and/or recurrent nonfatal myocardial infarction and/orcardiac death. The optimal IS cutoff value for MACE was determined by receiver operating character (ROC) curve. Based on the IS cutoff value, the patients were divided into the high IS group and the low IS group. Clinical characteristics between the two groups were compared. A cox regression model was used to analyze the prognostic value of IS in acute STEMI patients treated with primary PCI for the adverse events. Results: The IS cutoff value determined by ROC curve was 13.55%. 50 patients were in the high IS group (IS≥13.55%) and 54 patients were in the low IS group (IS<13.55%). More female patients [14 cases (28.0%) vs. 6 cases (11.1%)] were in the IS group, and a higher proportion of patients in the high IS group had anterior myocardial infarction [27 cases (54.0%) vs. 16 cases (29.6%)] or microvascular obstruction [32 cases (64.0%) vs. 16 cases (29.6%)]. White blood cell counts [11.25(8.90, 13.38) ×109/L vs. 9.25(7.58, 11.00) ×109/L], troponin I levels [50.63(16.56, 76.30)µg/L vs. 16.58(2.66, 38.42)µg/L] and brain natriuretic peptide levels [178.10(79.70, 281.95)µg/L vs. 79.60(42.83, 183.90)µg/L] in the high IS group were higher than those in the low IS group (P<0.05), and left ventricular ejection fraction [(45.15±10.65)% vs. (51.95±12.91)%] in the high IS group was lower than that in the low IS group (P<0.05). Multivariate Cox regression analyses showed that IS was independently associated with the risk of cardiac death in patients with acute STEMI two years after primary PCI(P=0.033, HR=1.075, 95%CI1.006-1.148). Every 1% increase in IS was associated with a 7.5% increase in cardiac death. Conclusions: Infarct size, measured by CMR within one week after primary PCI, is strongly associated with cardiac death in patients with acute STEMI two years after primary PCI. IS could be used as an index for the prognosis of patients with acute STEMI.

[Clinical analysis of surgical treatment of cornual pregnancy of 109 cases].

Objective: To study the clinical characteristics of cornual pregnancy and compare the effects of various surgical methods on the outcomes. Methods: This was a single-center retrospective study. The clinical records of patients with cornual pregnancy who underwent surgery in Peking Union Medical College Hospital from June 2012 to December 2020 were collected. Surgical interventions included curettage (guided by ultrasound or monitored by laparoscope), and cornuostomy/cornectomy (the surgical approach by laparoscopy or laparotomy). The baseline data, perioperative treatment and whether persistent ectopic pregnancy (PEP) occurred after surgery were collected and analyzed statistically. Results: A total of 109 patients with cornual pregnancy diagnosed by surgical treatment were included in this study, whose average age was (32.9±4.8) years. Among them, the incidence of postoperative PEP was 16.5% (18/109). The risk of PEP in multipara was significantly higher than that in nulliparous women (OR=7.639, 95%CI: 2.063-28.279, P=0.001). The risk of PEP in patients with the maximum diameter of lesion<1.5 cm was significantly higher than that in patients with the maximum diameter of lesion≥1.5 cm (OR=8.600, 95%CI: 2.271-32.571, P=0.002). Among all surgical approaches for cornual pregnancy, the proportion of PEP in curettage under ultrasound monitoring was the highest (56.0%, 14/25), which was higher than that in curettage under laparoscope monitoring (1/10; χ2=6.172，P=0.013); the proportion of PEP in curettage group (42.9%, 15/35) was higher than that in cornuostomy/cornectomy group (4.1%, 3/74; χ2=25.950，P<0.01). Neither salpingectomy in the operation nor the routine use of methotrexate (MTX) in perioperative period could significantly reduce the incidence of PEP (all P>0.05). Conclusions: Among the patients with cornual pregnancy, multipara, the maximum diameter of lesion<1.5 cm and ultrasound-guided curettage are the risk factors of PEP after operation. Cornuostomy or cornectomy is recommended for patients with cornual pregnancy. If the patients would perform the curettage operation, laparoscopic monitoring is recommended. For patients with possible satisfactory operation outcome, it is not recommended to use MTX as a routine preventing measure.

[Study on the expression of p62 protein in patients with lung adenocarcinoma].

To explore the expression of p62 protein in lung adenocarcinoma (LUAD). In this study, a cross-sectional study was adopted. From December 2011 to May 2013, 60 patients with lung adenocarcinoma who were diagnosed and treated in Tongji Hospital of Tongji University, Shanghai were selected for paraffin embedding and tissue chip preparation, and immunohistochemistry (IHC) technology was used to detect the expression of p62 in lung adenocarcinoma patients' cancer tissues and adjacent tissues, and analyze the relationship between p62 expression and the clinicopathological characteristics and survival prognosis of patients with lung adenocarcinoma; at the same time, 6 cases of lung adenocarcinoma were selected by random sampling cancer tissues and adjacent tissues were detected by Western Blot (WB) to detect p62 protein and analyzed by gray value. Preoperative examination specimens of inpatients with lung adenocarcinoma diagnosed from April 2018 to early October 2019, and plasma specimens of healthy subjects were collected, and enzyme linked immunosorbent assay (ELISA) was used to detect lung adenocarcinoma patients and healthy patients. The expression of p62 in the plasma of the subjects was statistically analyzed using SPSS 22.0 software. The results of IHC showed that the positive expression rate of p62 in cancer tissues was significantly higher than that in adjacent tissues, and the difference was statistically significant (t=5.593, P<0.001). Similarly, WB results showed that the expression of p62 protein in cancer tissues was significantly higher than that in adjacent tissues. It is statistically relevant (t=2.238, P=0.049). The expression of p62 was statistically correlated with tumor size, clinicopathological stage and lymph node metastasis in patients with lung adenocarcinoma (all P<0.05). The overall survival of patients with lung adenocarcinoma with high p62 expression was worse than that of patients with low p62 expression (95%CI was 0.238-0.870, P=0.028), suggesting that the high expression of p62 is related to the poor prognosis of patients with lung adenocarcinoma. The level of p62 protein in the plasma of patients with lung adenocarcinoma was significantly higher than that in the healthy control group. The difference was statistically significant (t=8.533, P<0.001). The area under the receiver operating characteristic curve was 0.835 (95%CI was 0.779-0.891, P<0.001), which is significantly higher than CEA, CA125, CA153 and other single traditional indicators, and the combined detection of four indicators has the highest diagnostic efficiency. p62 was strongly expressed in cancer tissues and serum, which is related to the poor prognosis and overall survival rate of LUAD patients.

[Application of deep learning neural network in pathological image classification of non-inflammatory aortic membrane degeneration].

Objective: To investigate the value of deep learning in classifying non-inflammatory aortic membrane degeneration. Methods: Eighty-nine cases of non-inflammatory aortic media degeneration diagnosed from January to June 2018 were collected at Beijing Anzhen Hospital, Capital Medical University, China and scanned into digital sections. 1 627 hematoxylin and eosin stained photomicrographs were extracted. Combined with the ResNet18-based deep convolution neural network model, 4-category classification of pathological images were performed to diagnose the non-inflammatory aortic lesion. Results: The prediction model of artificial intelligence assisted diagnosis had the best accuracy, sensitivity and precision in identifying lesions with smooth muscle cell nuclei loss, which were 99.39%, 98.36% and 98.36%, respectively. The classification accuracy of elastic fiber fragmentation and/or loss lesions was 98.08%, while that of intralamellar mucoid extracellular matrix accumulation lesions was 96.93%. The overall accuracy of the classification model was 96.32%, and the area under the curve was 0.982. Conclusions: The accuracy of deep learning neural network model in the 4-category classification of non-inflammatory aortic lesionsis confirmed based on digital photomicrographs. This method can effectively improve the diagnostic efficiency of pathologists.

Patient-derived organoids of non-small cells lung cancer and their application for drug screening.

Patient-derived organoids (PDOs) are emerging as preclinical models with promising values in personalized cancer therapy. The purpose of this study was to establish a living biobank of PDOs from patients with non-small cell lung cancer (NSCLC) and to study the responses of PDOs to drugs. PDOs derived from NSCLC were cultured in vitro, and then treated with natural compounds including chelerythrine chloride, cantharidin, harmine, berberine and betaine with series of concentrations (0.5-30 µM) for drug screening. Phenotypic features and treatment responses of established PDOs were reported. Cell lines (H1299, H460 and H1650) were used for drug screening. We successfully established a living NSCLC organoids biobank of 10 patients, which showed similar pathological features with primary tumors. Nine of the 10 patients showed mutations in EGFR. Natural compounds chelerythrine chloride, cantharidin and harmine showed anticancer activity on PDOs and cell lines. There was no significant difference in the 95% confidence interval (CI) for the IC50 value of chelerythrine chloride between PDOs (1.56-2.88 µM) and cell lines (1.45-3.73 µM, p>0.05). PDOs were sensitive to berberine (95% CI, 0.092-1.55 µM), whereas cell lines showed a resistance (95% CI, 46.57-2275 µM, p<0.0001). PDOs had a higher IC50 value of cantharidin, and a lower IC50 value of harmine than cell lines (p<0.05, 7.50-10.45 µM and 4.27-6.50 µM in PDOs, 3.07-4.44 µM and 4.69-544.99 µM in cell lines, respectively). Both PDOs and cell lines were resistant to betaine. Chelerythrine chloride showed the highest inhibitory effect in both models. Our study established a living biobank of PDOs from NSCLC patients, which might be used for high-throughput drug screening and for promising personalized therapy design.

[Clinical analysis of 68 cases of sepsis during pregnancy and the postpartum period].

Objective: To investigate the clinical features, etiology, and prognosis of sepsis during pregnancy and the postpartum period. Methods: Sixty-eight pregnant women with maternal sepsis treated in Peking Union Medical College Hospital from January 1997 to December 2019 were collected, and divided into obstetric infection group (30 cases) and non-obstetric infection group (38 cases) according to different infection sources. Clinical manifestations, types of infection sources, microbiological characteristics, treatment and outcomes were studied and analyzed. Results: (1) General conditions and clinical features: sepsis occurrence rate was 57% (39/68) and 43% (29/68) in prenatal and postpartum period, repectively. Statistical analysis showed that incidence of respiratory, renal, liver and coagulation dysfunction in non-obstetric infection group were significantly higher than those in obstetric infection group, and multiple organ dysfunction, cardiac arrest and blood lactate≥4 mmol/L were more common (all P<0.05). Sequential organ failure score in non-obstetric infection group was also significantly higher than that in obstetric infection group (P<0.05). (2) Types of infection sources and microbiological characteristics: the most common maternal sepsis was genital tract sepsis (37%, 25/68). Chorioamnionitis was the most common cause in obstetric sepsis (40%, 12/30), while intra-abdominal infection was the most common cause in non-obstetric sepsis (34%, 13/38). Thirty-seven patients (54%, 37/68) were diagnosed as bloodstream infection (BSI). Gram-negative bacteremia accounted for 70% (26/37), the most common pathogen of which was Escherichia coli. BSI was most commonly secondary to a genital tract infection (65%, 17/26). (3) Treatment: the ICU hospitalization rates and the utilization rate of mechanical ventilation and vasoactive agents in non-obstetric group were higher than those in obstetric group with significant differences (all P<0.05). Thirty-two patients (47%, 32/68) underwent surgery to remove the infection sources, including 5 cases of hysterectomy. (4) Prognosis: the case fatality rate of maternal sepsis was 19% (13/68), which was significantly higher in the non-obstetric infection group (29%,11/38) compared with the obstetric infection group (7%,2/30; P=0.020). The time from diagnosis of sepsis to termination of pregnancy was (5.5±8.6) days in prenatal women, and time in obstetric infection group [(1.9±2.2) days] was significantly less than that of non-obstetric infection group [(7.7±10.3) days, P=0.029]. Adverse pregnancy outcomes were higher in the first and second trimester (72%, 18/25) than in the third trimester (21%, 3/14), and the difference was statistically significant (P=0.002). Conclusions: Sepsis during pregnancy and the postpartum period is a potentially life-threatening disease. Pregnant women with non-obstetric sepsis have more complications, more serious condition and worse prognosis than those with obstetric infection. Timely detection of risk factors, early identification and active treatment are helpful to improve maternal and fetal prognosis.

[Postoperative distal tibiofibular synostosis: radiographic characteristics and the influence on ankle mobility].

Objective: To investigate the clinical and imaging characteristics of distal tibiofibular synostosis in postoperative ankle fractures and its effects on the ankle mobility. Methods: The clinical and imaging data of 47 patients with distal tibiofibular synostosis treated surgically from October 1991 to June 2013 were analyzed retrospectively. There were 30 males and 17 females, aged from 15 to 68 years with a mean age of (39±13) years. The original fracture types, internal fixation profiles, imaging features of distal tibiofibular synostosis were recorded. Ankle range of motion (ROM) and complications at the last follow-up were also evaluated.The ROMs of healthy and fractured sides were compared with paired sample rank test. Results: The patients were followed up for 3 to 204 months (mean 25.4 months). Of the patients, 34(72.4%) were ankle fractures, 7(14.9%) were distal tibiofibular fractures, 1(2.1%) was tibiofibular shaft fracture, 2(4.3%) were tibial shaft fractures associated with lateral malleolus fracture and the resting 3(6.4%) were Pilon fractures. In patients with ankle fractures, 76.5%(26/34) of the synostosis occurred at the distal tibiofibular syndesmosis, while 23.5%(8/34) at the proximal of the tibiofibular sydesmosis; in patients with distal tibiofibular fracture, 85.7%(6/7) of the tibiofibular synostoses occurred at the fracture sites. The synostosis occurred at the level of syndesmotic screws in 8 patients (88.9%, 8/9) fixed with distal tibiofibular syndesmotic screws. And synostosis occurred at the sites of the distal locking screws in all (3/3) of the patients fixed with intramedullary nails. At the last follow-up, the active plantarflexion, active dorsiflexion and passive dorsiflexion in the affected side was 0°(0°, 5°), 2°(0°, 5°), 5°(0°, 10°) less than those in the healthy side, respectively (Z=-3.493, -4.491, -5.130, all P<0.05).During the follow-up, 4 patients complained of lateral ankle discomfort with no impact on daily life. Conclusions: Post-operative distal tibiofibular synostosis mainly occurs at the sites of fractures, distal tibiofibular syndesmotic screw sites and the sites of the distal locking screws of tibial intramedullary nails. ROM of the injured ankle decreases in comparison with that at the contralateral side, although no obvious symptoms are observed and no intervention needed.

The terpenoid backbone biosynthesis pathway directly affects the biosynthesis of alarm pheromone in the aphid.

The terpenoid backbone biosynthesis pathway is responsible for the synthesis of different backbones for terpenoids; (E)-ß-farnesene (EßF), a sesquiterpene, is the major component of aphid alarm pheromone. Our previous studies eliminated the possibility of host plants and endosymbionts as the sources of EßF, and we thus speculate that the terpenoid pathway might affect the biosynthesis of EßF in aphids. First, the transcriptional responses of four genes encoding farnesyl diphosphate synthase (FPPS), geranylgeranyl diphosphate synthase (GGPPS) and decaprenyl diphosphate synthase in the cotton aphid Aphis gossypii to simulated stimulation were analysed using quantitative real-time PCR, showing an immediate decrease in the transcript abundances of the four genes. Next, RNA-interference-mediated gene knockdown was performed, indicating that fpps knockdown caused a significant cost in terms of body size and fecundity. Finally, an association analysis of gene knockdown with the amount of EßF was conducted, revealing that the concentration of EßF per milligram of aphid was drastically decreased in response to fpps knockdown, whereas ggpps knockdown significantly raised the concentration of EßF. Our data support a peculiar mode of biosynthesis and storage of the aphid alarm pheromone that relies directly on the terpenoid backbone biosynthesis pathway in the aphid.

Co-inhibitory immune checkpoints in head and neck squamous cell carcinoma.

The upregulation of co-inhibitory immune checkpoints hampers the immune response toward tumor cells and facilitates the tumor cells ability to evade immunosurveillance. Specific inhibitory immune checkpoint delivers inhibitory signals to T cells using multiple mechanisms. More in-depth understanding of the co-inhibitory immune checkpoints could be exploited for head and neck squamous cell carcinoma (HNSCC) treatment. In this review, we summarize the expression and the mechanism of partial co-inhibitory immune checkpoint signals and discuss targeting co-inhibitory immune checkpoints as an immunotherapeutic target for cancer therapy. This review may provide a better understanding of the co-inhibitory immune checkpoints and could promote applications of immunotherapy.

[Antimicrobial peptide LL-37 in macrophages promotes colorectal cancer growth].

Objective: To investigate the effect and molecular mechanism of antimicrobial peptide LL-37 secreted by stromal cells on the growth of colorectal cancer cells. Methods: Colorectal cancer cells SW480 or HCT116 were co-cultured with human macrophages using Transwell(®) maxicell inserts to mimic the tumor microenvironment. The effect of macrophages on the proliferation of colorectal cancer cells was detected by Bromodeoxyuridine and enzyme-linked immunosorbent assay (BrdU-ELISA). The expression of LL-37 mRNA and protein in macrophages and colorectal cancer cells was evaluated by reverse transcription-real-time quantitative PCR (RT-qPCR) and Western blot. LL-37 neutralizing antibody was added to abrogate the LL-37 activation. Additionally, macrophages were transfected with LL-37 shRNA plasmids to inhibit LL-37 expression. And then, the proliferation of colorectal cancer cells was observed. Furthermore, the growth-related signaling pathways were detected by Western blot. Results: The BrdU-ELISA results showed that the absorbance of SW480 cells increased from 1.072±0.097 to 5.121±0.407 after co-culture (P<0.001), and that of HCT116 cells increased from 1.229±0.073 to 3.495±0.228 (P<0.001). RT-qPCR results showed that LL-37 mRNA expression in macrophages significantly increased from 2.682±0.191 to 6.117±0.768 after co-incubation (P<0.05), whereas that in SW480 had no significant difference. Consistently the protein expression of LL-37 in macrophages was significantly increased by Western blot, while it did not change in SW480. The proliferation rate of SW480 cells was repressed by adding LL-37 neutralizing antibody or LL-37 shRNA plasmid. Furthermore, Western blot analysis showed that the expression of non-phosphorylated (activated) ß-catenin and its target genes cyclin D1 as well as c-myc were distinctly increased in co-cultured SW480 cells, which could be reversed by anti-LL-37 antibodies. Conclusion: Macrophages promote the in vitro proliferation of colorectal cancer cells by enhancing the expression and secretion of antimicrobial peptides LL-37, and it seems that LL-37 activates colorectal cancer cells via Wnt/ß-catenin pathway.

[Using creatinine reduction ratio as a predictor for delayed graft function of kindey transplant recipients from donor of cardiac death].

Objective: To explore the relationship between creatinine reduction ratio (CRR) and delayed graft function among kidney transplant recipients from donor of cardiac death (DCD). To define the value of CRR to predict delayed graft function (DGF) in early post-transplant period. Method: 86 patients were included, who received renal transplantation from DCD during Jan 1(st) 2011 to Jun 30(th) 2016. We performed a retrospective study and collected creatinine data within 3 days post-operation and marked them with Cr1, Cr2 , Cr3, and then calculated creatinine reduction ratio day-2 (CRR 2) =(Cr1-Cr2)/Cr1×100% and creatinine reduction ratio day-3 (CRR 3)=[(Cr1-Cr2)/Cr1+ (Cr2-Cr3)/Cr2]/2×100%. Patients were divided into two groups by DGF or not. We compared the CRR differenc between DGF group and no DGF group, and drew the receiver operating characteristic curve (ROC curve) to find out the cut-off value to predict delayed graft function. Results: Among 86 patients, DGF appeared in 17 patients. The incidence of DGF was 19.8%. The CRR 2 of patients in no DGF group was (37.5±17.4)% while patients in DGF group was (2.0±24.8)% (P<0.001). The CRR 3 of patients in no DGF group was (32.5±13.1)%, while patients in DGF group was (6.8±17.1)% (P<0.001). Acorrding to ROC curve, when cut-off value of CRR 2 was defined as <20.7%, the predicted value of DGF was the best, sensitivity was 85.5%, specificity was 76.5%, and area under the curve was 0.876. In the same way, when CRR 3 was defined as <17.6%, sensitivity was 89.9%, specificity was 76.5%, area under the curve was 0.872. Conclusion: It is reliable to predict DGF by CRR during early post-operative period. CRR shows high sensitivity and specificity and it is simple. It could guide the adjustion of immunosuppressive regimen, prevent early rejection and improve prognosis.

[Deltoid ligament augmentation and repairing in ankle fracture associated with deltoid ligament injury and syndesmosis diastasis].

Objective: To evaluate the outcome of the deep component augmentation and superficial component repairing and syndesmosis screw fixation in treating ankle fracture associated with deltoid ligament injury and syndesmosis diastasis. Methods: From January 2014 to December 2017, 16 patients with ankle fracture combined with deltoid ligament injury and syndesmosis diastasis were treated with the deep component augmentation and superficial component repairing in Beijing Jishuitan Hospital.Of the patients, 13 were males and 3 were females, with an average age of (38±10) years (21-57 years). Nine cases were athletic injuries, 4 cases were daily-life injuries and 3 cases were traffic injuries.According to the Weber classification, 6 cases were type B, 10 cases were type C. According to the Lauge-Hansen classification, 6 cases were supination external rotation Ⅳ injury, 9 cases were pronation external rotation Ⅳ injury, 1 case was pronation abduction Ⅲ injury.The surgical treatment method was rigid fixation of the lateral malleolus and deep deltoid ligament augamentation instead of syndesmosis screw fixation.The effect of the surgical method was observed. Results: The average follow up was (24±12) months (6-40 months). The mean degree of dorsiflexion was 17.8°±6.8° (5°-30°), with 3.8°±6.0° (0°-15°) less than that in normal side, the mean degree of plantar flexion was 46.9°±7.9°, with 1.9°±3.9° (0°-10°) less than that in normal side.The mean Philips and Schwartz score was 96.8±5.1 (82-100), the American Orthopaedic Foot and Ankle Society (AOFAS) Score was 97.4±4.6 (84-100). Conclusion: In the treatment of ankle fracture associated with deltoid ligament injury and syndesmosis diastasis, the deep component augmentation and superficial component repairing and proper rehabilitation can benefit the functional recovery.

[Analysis of clinical characters of female vulvar Paget disease].

Objective: To investigate the clinical and pathological features, diagnosis and treatment of primary vulvar Paget disease (VPD) , and analyze the related factors that may affect the recurrence. Methods: A retrospective study was carried out on 36 patients diagnosed as VPD pathologically from January 1983 to December 2017 at Peking Union Medical College Hospital, Chinese Academy of Medical Sciences. The clinical and pathological features, diagnosis, treatment and prognosis and the factors influencing recurrence rate of VPD were analyzed. Results: (1) Totally 94% (34/36) of VPD occurred in postmenopausal women. Pruritus was counted 86% (31/36) of the main complaint. Lesions of vulvar were main symptom which had no specificity, acting as ulcer (67%, 24/36) , erythema (50%, 18/36) , depigmentation (42%, 15/36) , sclerosis (31%, 11/36) , and pigmentation (17%, 6/36) . The lesions invaded labium majus (97%, 35/36) , sometimes labium minus (53%, 19/36) , clitoris (28%, 10/36) , perianal (25%, 9/36) , orificium vaginae (3%, 1/36) , and meatus urinarius (3%, 1/36) . Approximately 19% (7/36) of VPD coexisted with intraepithelial neoplasia or adenocarcinoma of vulvar or other part of body. (2) Diagnosis and treatment: diagnosis was confirmed histologically by biopsy or pathologies after surgery, and immunohistochemical results were helpful for differential diagnosis. Surgery was the mean treatment method, 34 of all the 36 patients (94%, 34/36) underwent surgery for at least once, while 2 patients (6%, 2/36) were performed non-operative treatment. The surgical treatment included excision of focus, wide local excision, simple vulvectomy, and extensive vulvectomy. The non-operative treatment included radiotherapy, chemotherapy, laser, photodynamic therapy, and so on. (3) Prognosis: among 36 VPD patients, 4 were lost to follow-up with a 89% (32/36) follow-up rate. Median follow-up was 35.3 months (range,1 month to 31 years) . During the follow-up period, 2 patients were unable to judge whether they will relapse for the follow-up time did not reach half a year, 8 cases were unsuccessful operation, 20 cases succeeded, the achievement ratio was 71% (20/28) . Nine of twenty cases relapsed, the recurrence rate was 45% (9/20) . The median recurrence time was 14 months after operation. One patient of the 32 followed-up patients died, the mortality rate was 3% (1/32) . (4) The related factors affected the recurrence of VPD: t test was applied to the analysis of patients' age, rank test was used in the statistics of the time of confirmed diagnosis, the length and thickness of the resection focus. Fisher test was used to calculate whether the focus were limited to the epidermis, type of surgical procedures, distance between the margin and the focus, whether tumor cells infiltrated the margin. The results showed that none of the above terms in the first operation had significant contribution to recurrence (all P>0.05) . Conclusions: VPD may be a low potential malignancy, which could slowly progress into deep invasive disease. VPD is often associated with intraepithelial neoplasia or primary tumors of the vulva or somewhere else. Operations is the first choice for VPD, but consider for its high recurrence rate after operation, close follow-up should be strongly suggested.

[Value of MRI in the pre-operative diagnosis and classification of oblique vaginal septum syndrome].

Objective: To explore the role of MRI in the pre-operative diagnosis and classification of oblique vaginal septum syndrome (OVSS) . Methods: A retrospective analysis of the clinical records and pre-operative MRI images of 19 patients with surgery proved OVSS was carried out. Two experienced radiologists reviewed the pre-operative pelvic MRI of the 19 patients in consensus blind to the surgery results. Characteristics including malformations of the uterus, cervix and vagina, the diagnosis of the disorder and classification were evaluated. Pre-operative MRI diagnosis and classification were correlated with surgical findings. Results: Mean age of onset of symptoms for the 19 patients was 15 years (ranged 9-25 years) , and mean age of menarche was 12 years. Ten patients suffered from dysmenorrhea or lower abdominal pain, 5 patients complained of vaginal discharge, 3 patients had a history of irregular menstruation, 1 patient suffered from primary infertility. All 19 patients showed uteri didelphys. Eighteen patients showed vaginal oblique septum.One patient showed cervical atresia.MRI was completely correlated with the surgery in the pre-operative diagnosis of OVSS. MRI classification was in line with surgery in 17 patients, including 9 patients with imperforate septum (typeⅠ) , 6 patients with perforate septum (type Ⅱ) , 1 patient with imperforate septum and cervical fistula (type Ⅲ) , and another one with cervical agenesis (type Ⅳ) . One case of type Ⅱ was misdiagnosed as type Ⅰ, another one of type Ⅰ was misdiagnosed as type Ⅲ. Pre-operative MRI classification was correlated with surgery in 17 out of 19 patients. Conclusion: Pre-operative MRI allows excellent manifestation and accurate diagnosis of OVSS, and could also facilitate the evaluation of the classification.

SATB1 promotes tumor metastasis and invasiveness in oral squamous cell carcinoma.

OBJECTIVE: Our aim is to evaluate the expression of SATB1 in human oral squamous cell carcinomas (OSCC) and its role in the invasiveness and metastasis of OSCC. SUBJECTS AND METHODS: A human OSCC tissue microarray was used to evaluate the expression pattern of SATB1. SATB1 mRNA knockdown was performed in human OSCC cell lines SCC25 and Cal27 to assess the function of SATB1 in the invasiveness and metastasis of OSCC. RESULTS: SATB1 is highly expressed in human OSCC determined by immunohistochemistry, and its nuclear/cytoplasmic ratio of histoscore is significantly correlated with patients' prognosis. Reduced cell motility, invasiveness, expression of epithelial to mesenchymal transition (EMT) markers (N-cadherin and ß-catenin), and elevated expression of epithelial markers were observed in SATB1-knockdown cells in in vitro studies. Depletion of SATB1 also restored a cobblestone-like morphology in TGF-ß1-treated cells. CONCLUSIONS: These findings suggest SATB1 may play an important role in OSCC invasiveness and metastasis.

[Effect of intermittent negative pressure on matrix metalloproteinase 9 and transforming growth factor ß of tendon-bone interface and joint fluid after reconstruction of anterior cruciate ligament in rabbits].

Objective: To study the effect of intermittent negative pressure on matrix metalloproteinase 9 (MMP)-9 and transforming growth factor ß of tendon-bone interface and joint fluid after reconstruction of anterior cruciate ligament in rabbits. Methods: A total of twenty-four New Zealand white rabbits were randomly selected hind leg of negative group, contralateral hind leg as control.Reconstruction of the anterior cruciate ligament was done by autogenous semitendinosus of rabbit.Joint of the negative pressure side placed drainage tube connecting the micro-negative pressure aspirator, and maintained an intermittent, low-intensity negative pressure.Control side placed ordinary drainage tube.Drainage tube of both sides was pulled out at the same time after 5 days.After 6 weeks, joint fluid and femur-ligament-tibia complex were obtained for study of expression of MMP-9 and TGF-ß in joint fluid and tendon-bone interface. Result: Twenty-three rabbits were included in the study because of one rabbit joint infections.Detection of joint fluid showed that MMP-9 content is significantly lower in negative group than that in the control group, and the difference is statistically significant [(8.9±1.3) pg/L vs (12.3±1.8) pg/L (P=0.002)]. TGF-ß content is significantly higher in negative group in joint fluid than that in the control group, and the difference is statistically significant [(19.0±2.2) pg/L vs (15.2±1.4) pg/L (P=0.000)]. Study of immunohistochemistry in tendon-bone interface found that expression of MMP-9 is lower in negative pressure group than that in the control group, and the difference is statistically significant (P=0.000). TGF-ß expression is significantly higher in negative group in tendon-bone interface than that in the control group, and the difference is statistically significant (P=0.000). Conclusion: Intermittent negative pressure may reduce content of MMP-9 in joint fluid and expression of MMP-9 in tendon-bone interface, increase content of TGF-ß in joint fluid and expression of TGF-ß in tendon-bone interface after reconstruction of anterior cruciate ligament in rabbits.