[Transoral robotic thyroidectomy via vestibular approach: a retrospective study of 107 cases in a single center].

Objective: To investigate the short-term outcome of transoral robotic thyroidectomy. Methods: This is a retrospective case series study. The clinicopathologic characteristics and postoperative results of 107 patients who underwent transoral robotic thyroidectomies in the Department of Thyroid and Breast Surgery of the 960th Hospital of People's Liberation Army from May 2020 to August 2023 were retrospectively analyzed. There were 12 males and 95 females, with an age of (31.8±9.4) years (range: 11 to 55 years), including 20 benign tumors and 87 thyroid papillary carcinoma. Postoperative follow-up was carried out through returning visit and telephone, mainly to observe the recovery of postoperative complications, cosmetic effects and recurrence results. Results: All transoral robotic thyroidectomy was successfully completed without conversion to open surgery. The tumor size of thyroid papillary carcinoma patients was (5.6±2.7) mm (range: 2 to 15 mm). Furthermore, central cervical lymph node metastasis was found in 45 cases. The number of central cervical lymph nodes retrieved and metastasized (M(IQR)) were 11 (8) (range: 3 to 26) and 1 (3) (range: 0 to 13), respectively. There was no recurrent laryngeal nerve injury and permanent hypoparathyroidism. The transient hypoparathyroidism after surgery was 8 cases. Other complications occurred as follows: postoperative infection (n=1), left submandibular perforation (n=1), skin scald (n=1), and perioral numbness (n=1), oral tear (n=2). The postoperative stay was 6 (2) days (range: 3 to 11 days). No local lymph node recurrence or metastasis occurred after a follow-up of (22.6±10.0) months (range: 1.0 to 37.4 months). All patients were satisfied with the postoperative cosmetic results, the aesthetic effect score was 9.3 (0.2) (range: 8.4 to 9.6) one month after surgery. Conclusion: For highly screened patients with early thyroid cancer, experienced surgeons can perform a transoral robotic thyroidectomy that has excellent cosmetic results.

[A retrospective comparative study between robotic thyroidectomy through transoral vestibular approach and bilateral breast-axillary approach].

Objective: To compare the surgical outcome of robotic thyroidectomy through transoral approach and the bilateral breast-axillary approach. Methods: Retrospective analysis was made on the clinical data of patients who performed transoral robotic thyroidectomy (TORT group) or bilateral breast-axillary approach (BABA group) in the Department of Thyroid and Breast Surgery, the 960th Hospital of People's Liberation Army from July 2020 to May 2022. Both groups received lobectomy with lymph node dissection of the central region. A total of 100 cases were included in the study, including 48 cases in the TORT group and 52 cases in the BABA group. The propensity score matching method was used for 1∶1 matching of patients between the 2 groups, with a match tolerance of 0.03. There were 31 patients in each group successfully matched. In the TORT group, there were 5 males and 26 females, aged (33.2±7.9) years (range: 21 to 53 years). While there were 4 males and 27 females in the BABA group, aged (34.6±9.2) years (range: 19 to 58 years). The t test, Mann-Whitney U test, χ2 test or Fisher exact test were used to compare the clinical efficacy between the two groups. Results: All the patients successfully completed robotic thyroid surgery without conversion to open surgery. Compared with BABA group, the TORT group had longer operation time ((211.3±57.2) minutes vs. (126.2±37.8) minutes, t=6.915, P<0.01), shorter drainage tube retention time ((5.4±1.0) days vs. (6.4±1.2) days, t=-3.544, P=0.001), shorter total hospital stay ((6.6±1.2) days vs. (7.4±1.3) days, t=-2.353, P=0.022), and higher cosmetic score (9.46±0.25 vs. 9.27±0.26, t=2.925, P=0.005). There was no significant difference between the two groups in the number of lymph nodes dissection, metastasis in the central compartment, and the incidence of postoperative complications (all P>0.05). Conclusions: Compared with the bilateral breast-axillary approach, the transoral vestibular approach of robotic thyroidectomy is also safe and effective. It shows similar surgical results to the bilateral breast-axillary approach in strictly selected patients, but the postoperative recovery speed is much faster, and the hospital stay is shorter. Transoral robotic thyroidectomy is a more recommended surgical method for patients with high aesthetic demand.

[Preliminary application of transoral robotic thyroidectomy: experience from an initial 30 cases].

Objective: To examine the surgical outcome of transoral robotic thyroidectomy. Methods: Clinic data of total 30 cases of transoral robotic thyroidectomy at the Department of Thyroid and Breast Surgery, the 960th Hospital of People's Liberation Army from May 2020 to December 2020 were analyzed retrospectively. There were 3 males and 27 females, aged (31.5±11.0) years (range: 17 to 55 years), including 6 cases of benign tumor and 24 cases of malignant cancer (all papillary thyroid carcinoma). An inverted U-shaped incision 1.5 cm in length was made over the end of the frenulum of the lower lip. A wide subplatysmal space was created by bluntly passing with a vascular tunneller (8 mm diameter), and a 12 mm trocar was inserted through the lip incision for the camera port. Lateral oral mucosal incisions 8 mm in length were made near both lateral labial commissures, 8 mm robot trocars were inserted through the incisions. An 5 mm trocar was inserted through an incision made along the patient's right axillary fold into the subplatysmal working space and was connected with 5 mm ProGrasp for counter traction during the operation and for later drain insertion. Numerical scoring system (NSS) was used to assess cosmetic effect 1 month post-operation. Results: All the 30 transoral robotic thyroidectomies was successful, no case conversed to open operation. Postoperative hospital stay was (6.3±1.2) days (range: 4 to 10 days). The tumor size of thyroid cancers was (5.3±3.0) mm (range: 2 to 15 mm). Lymph node metastasis was observed in 12 cases. The retrieved central lymph node number was 10.5±4.4 (range: 4 to 20), while the central metastatic lymph node number was 2(2) (range: 1 to 11). Postoperative transient hypoparathyroidism occurred in 2 cases. Permanent hypoparathyroidism and vocal cord palsy didn't occur. Other surgical complications included hematoma, surgical site infection and perforation of chin flap, retrospectively in 1 case. Local regional lymph node recurrence wasn't developed during 1 to 7 months follow-up. All patients were satisfied with the postoperative cosmetic outcomes,NSS was 9.4±0.8 (range: 8.7 to 9.6). Conclusion: Transoral robotic thyroidectomy is safe and effective, suitable for early thyroid cancers without lateral lymph node metastasis, and has superior cosmetic results when the patients are selected carefully.

[Outcomes of 1 000 cases of robotic thyroidectomy by bilateral axillo-breast approach: a retrospective study in a single center].

Objective: To examine the surgical outcome, completeness and safety of robotic thyroidectomy by bilateral axillo-breast approach (BABA). Methods: From February 2014 to May 2019, 1 000 cases of robotic thyroidectomy via BABA at the Department of Thyroid and Breast Surgery, the 960th Hospital of People's Liberation Army were performed. The clinicopathologic characteristics, operation times, perioperative complications, and oncologic outcomes of patients underwent robotic thyroidectomy were collected and reviewed retrospectively. There were 216 males and 784 females, aging (42.3±11.5) years (range: 7 to 75 years). There were 270 cases with benign tumors, and 730 cases with malignant cancers (the tumor diameter was (7.9±6.7) mm (range: 0.1 to 60.0 mm)). Results: There were 999 patients received robotic thyroidectomy using BABA approach successfully, while only 1 case conversed to open operation. The postoperative hospital stay was (7.5±2.5) days (range: 2 to 30 days). Among the 730 patients with thyroid cancers, 725 cases (99.3%) were papillary thyroid carcinoma, 579(79.3%) cases were with papillary thyroid microcarcinoma. Lymph node metastasis was observed in 371(50.8%) cases. The retrieved central lymph node number was 11.2±6.1 (range: 1 to 44),and the retrieved lateral lymph node number was 14.0±8.8 (range: 1 to 52). Postoperative transient hypoparathyroidism and vocal cord palsy occurred in 247(24.70%) and 56(5.60%) cases. Both of permanent hypoparathyroidism and vocal cord palsy occurred in 2 (0.20%) cases. Other surgical complications included chyle leakage (6.1%, 28/460), trachea injury (0.40%, 4/1 000), carotid artery injury (0.10%, 1/1 000). Local regional lymph node recurrence was developed in 4 patients. All patients were satisfied with the postoperative cosmetic outcomes. Conclusions: Robotic thyroidectomy by BABA is safe and effective, suitable for large benign tumors and early thyroid cancers with central or lateral lymph node metastasis. It could obtain superior cosmetic results.

[A predictive model based on risk factors for early mortality in patients with newly diagnosed multiple myeloma].

Objective: To investigate risk factors for early mortality (EM) in patients with newly diagnosed multiple myeloma (NDMM) and to build an EM-predictive model. Methods: In a cohort of 275 patients with NDMM, risk factors for EM at 6, 12, and 24 months after diagnosis (EM6, EM12, and EM24, respectively) were determined to establish a model to predict EM. Results: The rates of EM6, EM12, and EM24 were 5.5% , 12.7% , and 30.2% , respectively. The most common cause for EM was disease progression/relapse, accounting for 60.0% , 77.1% , and 84.3% of EM6, EM12, and EM24, respectively. EM6 was associated with corrected serum calcium >2.75 mmol/L and platelet count <100×10(9)/L, whereas risk factors for EM12 included age >75 years, ISS Ⅲ, R-ISS Ⅲ, corrected serum calcium >2.75 mmol/L, serum creatinine >177 µmol/L, platelet count <100×10(9)/L, and bone marrow plasma cell ratio ≥ 60% . In addition to the risk factors for EM12, EM24 was also associated with male sex and 1q21 gain. By multivariate analysis, age >75 years, platelet count <100×10(9)/L, and 1q21 gain were independent risk factors for EM24 but there were no independent risk factors significantly associated with EM6 and EM12. Using a scoring system including these three risk factors, a Cox model for EM24 was generated to distinguish patients with low (score<3) and high (score ≥ 3) risk. The sensitivity and specificity of the model were 20.7% and 99.2% , respectively. Further, an internal validation performed in a cohort of 183 patients with NDMM revealed that the probability of EM24 in high-risk patients was 26 times higher than that in low-risk patients. Moreover, this model was also able to predict overall survival. The median overall survival of patients with scores of 0, 1, 2, 3, 4, and 5 were 59, 41, 22, 17.5, and 16 months, respectively. Conclusion: In the study cohort, the EM6, EM12, and EM24 rates were 5.5% , 12.7% , and 30.2% , respectively, and disease progression or relapse were main causes of EM. An EM24-predictive model built on three independent risk factors for EM24 (age>75 years, platelet count<100×10(9)/L, and 1q21 gain) might predict EM risk and overall survival.

[Complications of Da Vinci robot thyroid surgery by bilateral axillo-breast approach].

Objective: To evaluate the complications of Da Vinci robotic thyroid surgery by bilateral axillo-breast approach. Methods: A retrospective analysis of complications was conducted on 1, 198 cases of Da Vinci robotic thyroid surgery by bilateral axillo-breast approach of the 960 th Hospital of the People's Liberation Army from February 2014 to March 2020. There were 263 men and 935 women, age ranged from 9 to 68 years old, and included 288 benign lesions and 910 malignancies according to preoperative imaging examination, FNAC, and intraoperative frozen pathology. Results: Surgical complications occurred in 187 (15.61%) patients, including 10 cases of temporary larynx nerve injury (0.83%), 1 case of permanent larynx nerve injury (0.08%), and 152 cases of temporary hypoparathyroidism (12.69%), no permanent hypoparathyroidism, 1 case of hypoglossal injury (0.08%), 2 cases of facial nerve jaw branch damage (0.17%), 2 cases of trachea injury (0.17%), no esophagus damage, 5 cases of celiac leakage (0.42%), 3 cases of neck skin adhesion (0.25%), 2 cases of subdermal bleeding (0.17%), 2 cases of skin burns (0.17%), 5 cases of hematoma (0.42%), 1 case of cephalic artery rupture (0.08%), 1 case of jugular vein rupture (0.08%), no tumor cultivation, no arm plex nerve, accessory nerve or phrenic nerve damage. Conclusion: Da Vinci robot thyroid surgery by bilateral axillo-breast approach is safe, with less severe complications.

[Adverse effects of double-hit combining ISS-â ¢ stage and 1q gain or del (17p) on prognosis of patients with newly diagnosed multiple myeloma].

Objective: To evaluate the prognostic significance of combining ISS-Ⅲ and high risk cytogenetic abnormalities [HRCAs, including 1q gain/amplification and del (17p) ] in patients with newly-diagnosed multiple myeloma (NDMM) . Methods: The clinical characteristics and relevant variables were retrospectively analyzed in a total of 270 NDMM patients diagnosed between November 2009 and May 2018. ISS-Ⅲ stage and HRCAs [detected by FISH, including 1q gain/amplification and del (17p) ] were defined as risk factors (hit) . Based to the number of hit per case, these patients were divided into four groups carrying 0 to 3 risk factors, respectively. Progress-free survival (PFS) and overall survival (OS) were then analyzed using the Kaplan-Meier estimator. Results: Patients who carried single hit (n=120, 44.4%) had shorter median PFS (23.0 vs 28.9 months; P>0.05) and OS (42.3 vs 53.7 months; P>0.05) than those with no risk factors (n=66, 24.4%) . Of note, the outcome of patients who had two or more risk factors (double/triple, n=84, 31.1%) was much worse than those with either no or one risk factor, indicated by significantly reduced median PFS (14.5 months; HR=1.584, 95%CI 1.082-2.319; P=0.003 for double/triple vs single hit) and OS (18.4 months, HR=2.299, 95%CI 1.485-3.560; P<0.001 for double/triple vs single hit) . Strikingly, patients who had three risk factor (triple hit, n=5, 1.9%) displayed the poorest survival with extraordinarily shorter PFS (0.9-15.1 months) and OS (0.9-18.9 months) compared to those carrying two risk factors (double hit) . Analogous results were obtained when different combinations of ISS stages and HRCAs were analyzed. Conclusion: These results suggest a potential but rather important role of combining multiple (e.g. double or triple) adverse factors determined via the routine ISS staging and FISH detection of cytogenetic abnormalities in risk stratification and prognostic prediction, which might be helpful to identify high risk patients more precisely at diagnosis. It also raised a possibility that a small group of ISS-Ⅲ patients carrying both 1q gain/amplification and del (17p) might represent an "extremely-high risk" subset of MM.

Structure and mode of action of a novel antibacterial peptide from the blood of Andrias davidianus.

Andrias davidianus is widely recognized in traditional medicine as a cure-all to treat a plethora of ailments. In a previous study, a novel antibacterial peptide named andricin B was isolated from A. davidianus blood. In this study, we investigated andricin B structure and its mode of action. Circular dichroism spectra suggested that andricin B adopts a random coil state in aqueous solution and a more rigid conformation in the presence of bacteria. Moreover propidium iodide/fluorescein diacetate double staining indicated that bacteria treated with andricin B were not immediately eliminated. Rather, there is a gradual bacterial death, followed by a sublethal stage. Scanning electronic microscope imaging indicates that andricin B might form pores on cell membranes, leading to the release of cytoplasmic contents. These results were consistent with flow cytometry analysis. Furthermore, Fourier transform infrared spectroscopy suggests that andricin B induces changes in the chemical properties in the areas surrounding these "pores" on the cell membranes. SIGNIFICANCE AND IMPACT OF THE STUDY: The results of this study suggested the new perspectives about the mode of action of antimicrobial peptide (AMP) active against sensitive bacteria. The AMP was able to be in a random coiled state in aqueous solution but to change to a more rigid one in the presence of sensitive bacteria. Exposure to AMP might not lead to immediate death of treated bacteria, rather bacteria concentration decreased gradually flattening at a sublethal stage. These findings will help people to understand better how the AMPs activate against sensitive bacteria.

[Prognostic analysis of 182 newly diagnosed multiple myeloma patients with high risk cytogenetic abnormalities].

Objectives: To evaluate the clinical characteristics and prognosis of high risk cytogenetic abnormalities (HRCA) and various combinations of cytogenetic abnormality in patients with newly-diagnosed multiple myeloma (NDMM) . Methods: This retrospective study collected 182 NDMM patients in the First Affiliated Hospital of Jilin University between Nov. 2009 and May 2018. HRCA included 1q+, del (17p) , t (4;14) , and t (14;16) detected by FISH, and non-HRCA included del (13q) , t (11;14) detected by FISH. The clinical characteristics among three groups, including cases who carrying a single HRCA, 1 HRCA in combination with non-HRCA and cases carrying two or more HRCAs (double/triple-hit) were observed. Kaplan-Meier curve was used to analyze both progression-free survival (PFS) and overall survival (OS) for the three groups. Results: The survivals of patients with 1 HRCA in combination with non-HRCA were similar to those with two or more HRCAs (double/triple-hit) , the median PFS (mPFS) was 19.1 m vs 12.1 m (P=0.248) and median OS (mOS) was 29.6 m vs 29.3 m (P=0.774) . Furthermore, the prognosis of these two groups were both inferior to patients with a single HRCA, respectively. (mPFS: 32.2 m, P=0.040, P=0.001; mOS: 42.3 m, P=0.021, P=0.041) . Strikingly, both the mPFS and the mOS of patients with 1 HRCA in combination with non-HRCA (regardless of high risk or not) were significantly shorter than that of cases with a single HRCA (mPFS: 15.1 m vs 32.2 m, HR=2.126, 95%CI 1.176-3.843, P=0.005; mOS: 29.3 m vs 42.3 m, HR=1.442, 95%CI 0.705-2.950, P=0.011) . Conclusion: It is of prognostic significance value for detecting double/triple-hit based on FISH cytogenetics in NDMM.

[LIG4 syndrome: a report of four cases and literature review].

Objective: To analyze clinical, immunological and genetic characteristics of 4 cases of LIG4 syndrome. Methods: We retrospectively analyzed the clinical data of 4 patients from 3 families with LIG4 syndrome who were admitted to Children's Hospital of the Capital Institute of Pediatrics from June 2017 to May 2018, and reviewed related articles, the clinical, immunological and genetic characteristics of LIG4 syndrome were summarized and analyzed. Results: Those 4 cases (P1 to P4), including 2 males and 2 females, had an average age of 1.5 years. All of them presented with special facial features, such as microcephaly, beak-like-nose, and receding forehead. Three of them presented with delayed physical development. P3 suffered from mental retardation and P4 had feeding difficulty. BCG scars were repeatedly ruptured in 3 cases, 4 cases had pneumonia, 1 case had EB virus infection, 2 cases had cytomegalovirus infection, 1 case had fungal infection, and 1 case had chronic diarrhea. Blood routine tests showed decreased neutrophil and lymphocyte counts. Immunoassay showed decreased absolute count of CD4(+)T lymphocyte and B lymphocyte, with normal CD8(+)T cells. P1, P2 presented with decreased immunoglobulin. All of those patients had LIG4 gene complex heterozygous mutations, of whom one had missense mutation had mild clinical phenotype and another three cases had frameshift mutation presented with severe clinical phenotype. One patient underwent hematopoietic stem cell transplantation, and has established normal immune function. He did not have recurrent infection during one year follow-up period. The other 3 patients had preventive anti-infection treatment and received regular human immunoglobulin infusion, but they still had recurrent infection. In literature review, 67 articles were retrieved, totally 37 case were reported, showing special faces and recurrent infection as characteristic presentation of this disease. Conclusions: The typical manifestations of LIG4 syndrome are microcephaly, special facial features and repeated infection. The average age at diagnosis of LIG4 syndrome was more than one year old. If a patient presented with microcephaly, BCG scar infection and leukopenia, LIG4 syndrome should be considered. Immunoglobulin is decreased at different degrees, and CD4(+) and CD19(+) lymphocyte counts always decrease, Naive T and B cells decrease more prominently, and CD8(+)T cells were normal in patients with typical LIG4 syndrome. It is effective to reconstruction of immune system with bone marrow transplantation in LIG4 syndrome patients.

[The prognostic significance of dynamic monitoring of minimal residual disease (MRD) status in patients with newly-diagnosed multiple myeloma].

Objective: To evaluate the prognostic value of kinetic changes in minimal residual disease (MRD) status, as well as its relationship with risk stratification, therapeutic response and treatment in patients with newly-diagnosed multiple myeloma (MM) . Methods: A total of 135 patients with newly-diagnosed MM were screened, and 105 patients who achieved VGPR or more as the best responses were included into this study. The MRD status was determined by multiparameter flow cytometry (MFC) at multiple intervals after two cycles of treatment until clinical relapse, death, or last follow-up. The statistical methods included Kaplan-Meier analysis, Cox regression, etc. Results: ①In all 135 patients, 57.8% (78/135) patients achieved MRD negativity (MRD(-)) after treatment. In 105 patients who achieved VGPR and thus included in this study, the MRD(-) rate was 72.4% (76/105) , with a median interval of 3 months from starting treatment to achievement of MRD(-) status. ②The 2-year PFS rate of patients with MRD(-) status was significantly higher than that of MRD(+) status (62.2% vs 41.3%, P=0.001) , while MRD persistence (MRD(+)) was an independent factor for poor prognosis (multivariate analysis for PFS: P=0.044, HR=3.039, 95%CI 1.029-8.974) . ③Loss of MRD(-) status (i.e., MRD reappearance) showed inferior outcomes compared with MRD sustained negative ones, the PFS was 18 months versus not reach (P<0.001) and the OS was not reach for both (P=0.002) . ④The 2-year PFS and OS rates of patients with duration of MRD(-)status≥12 months were significantly higher than those of the control group (PFS: 77.7% vs 36.7%, P<0.001; OS: 96.4% vs 57.9%, P<0.001 respectively) . Duration of MRD(-) status was associated with a marked reduction in risk of relapse or death (univariate analysis for PFS: P<0.001, HR=0.865, 95%CI 0.815-0.918; for OS: P=0.001, HR=0.850, 95%CI 0.741-0.915 respectively) . ⑤Moreover, even in patients carrying high-risk cytogenetic abnormalities (CA) or ineligible for ASCT, MRD negativity remained its prognostic value to predict PFS (high-risk CA medianPFS: not reach vs 19 months, P=0.006; ineligible for ASCT medianPFS: not reach vs 25 months, P=0.052 respectively) . ⑥Last, treatment with the bortezomib-based regimens contributed to prolonged MRD(-) duration (median MRD(-) duratio: 25 months vs 10 months, P=0.034) . Conclusion: Our findings supported MRD(+) status as an independent poor prognostic factor in MM patients, which implicated that duration of MRD(-) status also played a significant role in evaluation of prognosis, while loss of MRD(-)status might serve as an early biomarker for relapse. Therefore, monitoring of MRD kinetics might more precisely predict prognosis, as well as guide treatment decision, especially for when to start retreatment in relapsed patients.

[Application of da Vinci robot's bilateral axillo-breast approach in thyroid surgery of obese patients].

Objective:To discuss the effect of obesity on the operation of thyroid gland surgery and surgical results.Method:The clinical data of 446 patients who underwent robot thyroid surgery through bilateral axillo-breast approach (BABA) from the General Hospital of Jinan Military region from February 2014 to November 2017 were analyzed retrospectively, and the patients were divided into BMI<25 kg/m²; group, BMI 25-30 kg/m²; group and BMI>30 kg/m²; group according to body mass index (BMI). The operative complications were compared between the three groups of benign and malignant patients, such as operation time, postoperative lead flow, postoperative hospitalization time, tumor size (malignant), lymph node metastasis (malignant), cosmetic satisfaction score, laryngeal nerve injury and parathyroid function decrease. Statistical methods using Variance analysis and χ² test to compare the differences between the two groups of indicators, difference is statistically significant (P<0.05).Result:The difference of operation time, postoperative average hospitalization time and postoperative drainage fluid volume in 3 groups was not statistically significant（P>0.05）. ①Intraoperative and postoperative pathological results were benign: BMI<25 kg/m²; group 69 cases, BMI 25-30 kg/m²; group 48 cases, BMI>30 kg/m²; group 8 cases, temporary recurrent laryngeal nerve injury were 1 case, 0 case and 0 case respectively, temporary parathyroid function decrease 3 cases, 2 cases and 1 case. ②Intraoperative and postoperative pathological results were malignant:BMI<25 kg/m²; group 180 cases, BMI 25-30 kg/m²; group 119 cases,BMI>30 kg/m²; group 22 cases, temporary recurrent laryngeal nerve injury were 2 cases,1 case and 0 case respectively, temporary parathyroid dysfunction in 64 cases,29 cases and 5 cases respectively.③1 patient in BMI<25 kg/m²; group had lymphatic leakage after operation, 1 patient in BMI 25-30 kg/m²; group had subcutaneous tunnel hemorrhage, and 1 patient had lymphatic leakage during operation.Conclusion:For overweight or obese patients, the da Vinci robot thyroid operation is reliable, does not increase the risk of surgical complications, but also has a good cosmetic effect.

[Relationship of HPV infection and BV, VVC, TV: a clinical study based on 1 261 cases of gynecologic outpatients].

Objective: To Explore the relationship between HPV infection and bacterial vaginosis(BV), vulvovaginal candidiasis(VVC), and trichomonal vaginitis(TV). Methods: Clinical data from 1 261 gynecologic outpatients who underwent the vaginal microecology and HPV type detection during June 2015 to December 2015 were collected and analyzed in the First Affiliated Hospital of Xi'an Jiaotong University. Results: In 1 261 patients, 328 cases infected with HPV, infection rate was 26.01%(328/1 261); vaginal infectious disease in 328 cases of HPV infections were 219 cases(66.8%, 219/328), vaginal infectious diseases in 933 cases of HPV uninfected were 503 cases(53.9%, 503/933), incidence of vaginal infectious disease in HPV infected patients was higher than that in HPV uninfected patients(χ2=5.87, P=0.01). 142 cases of BV had 54 cases infected with HPV(38.0%, 54/142), 296 cases of intermediate type BV had 88 cases infected with HPV(29.7%, 88/296), 231 cases of normal vaginal microecology had 51 cases infected with HPV(22.1%, 51/231), 99 cases of VVC had 15 cases infected with HPV(15.2%, 15/99), 2 patients with TV had 0 cases infected with HPV(0/2), HPV infection rate in BV, intermediate type BV patients were significantly higher than normal patients(P<0.05), while there were no statistical differences among VVC, TV and normal patients(P>0.05). The intensity of HPV infection were positively correlated with BV, intermediate type BV(OR=2.17, 95% CI: 1.37-3.43, P<0.01; OR=1.49, 95% CI: 1.00-2.22, P= 0.04); while, VVC, TV were uncorrelated with HPV infection(all P>0.05). Conclusions: BV, intermediate type BV are positively correlated with HPV infection, especially for the high-risk HPV. VVC and TV are not correlated with HPV infection.

An in vivo model for the study of ovarian cancer and the persistence of characteristic mutations in xenografts.

OBJECTIVE: To identify factors affecting xenograft growth of epithelial ovarian cancer (EOC) cells in nude mice and to detect characteristic mutations occurring in the xenografts following serial passage. MATERIALS AND METHODS: A total of 64 human EOCs were subcutaneously inoculated in Balb/c nude mice in order to obtain a series of xenografts. Whole-exome sequencing was analyzed with Agilent SureSelect targeted enrichment capture system and Illumina Solexa Hiseq 2000 sequencing platform. Mutations were confirmed by comparison against the reference genome build 37.3. RESULTS: The tumor take rate was 50% (32/64). TP53 mutation was detected in nine often Type II tumors. BRAF and CTNNB1 were not mutated in any of the samples, and PTEN mutation occurred in only one sample. The present data indicate that advanced stage serous EOCs and early stage non-serous EOCs were easy to grow in nude mice, and xenografts maintained the characteristic mutations. CONCLUSIONS: Advanced stage serous EOCs and early stage non-serous EOCs were easy to grow in nude mice, and xenografts maintained the characteristic mutations. Xenografts in nude mice are useful in vivo models for the study of human EOCs.

Purification and identification of five novel antioxidant peptides from goat milk casein hydrolysates.

The present research described the preparation, purification, and identification of antioxidant peptides from goat milk casein (GMC). Goat milk casein was hydrolyzed by using a combination of neutral and alkaline proteases to obtain goat milk casein hydrolysates (GMCH) with high antioxidant activity. After desalting by nonpolar macroporous absorption resin, GMCH was isolated and purified by gel filtration chromatography and reversed-phase HPLC, respectively, and further identified by nanoliter electrospray ionization-tandem mass spectrometry. Antioxidant activities of GMC, GMCH, and pure peptides were evaluated and compared using free radical scavenging activity, metal ion chelating ability, and anti-lipid peroxidation ability. Compared with GMC, the free radical-scavenging ability and ferrous ion-chelating ability of GMCH increased significantly. The inhibition effect of lipid peroxidation of GMCH was much stronger than that of tert-butylhydroquinone and phytogermine and a little lower than that of ascorbic acid. The antioxidant activity of GMCH could be attributed to the high antioxidant activity of oligopeptides, especially 5 novel oligopeptides: Val-Tyr-Pro-Phe, Phe-Gly-Gly-Met-Ala-His, Phe-Pro-Tyr-Cys-Ala-Pro, Tyr-Val-Pro-Glu-Pro-Phe, and Tyr-Pro-Pro-Tyr-Glu-Thr-Tyr, which were first observed in GMCH. The antioxidant activity of these 5 novel oligopeptides and GMCH increased 3.59 to 380 times compared with GMC, combining anti-lipid peroxidation ability of GMCH, which indicated that GMCH and its purified fractions in different stages could be used as functional food ingredients, food additives, and pharmaceutical agents in the future.

Postconditioning with a volatile anaesthetic in alveolar epithelial cells in vitro.

Acute lung injury is a common complication in critically ill patients. The present study examined possible immunomodulating effects of the volatile anaesthetic sevoflurane on lipopolysaccharide (LPS)-stimulated alveolar epithelial cells (AEC) in vitro. Sevoflurane was applied after the onset of injury, simulating a "postconditioning" scenario. Rat AEC were stimulated with LPS for 2 h, followed by a 4-h co-exposure to a CO(2)/air mixture with sevoflurane 2.2 volume %; control cells were exposed to the CO(2)/air mixture only. Cytokine-induced neutrophil chemoattractant-1, monocyte chemoattractant protein-1, intercellular adhesion molecule-1, as well as the potential protective mediators inducible nitric oxide synthase (iNOS)2 and heat shock protein (HSP)-32, were analysed. Additionally, functional assays (chemotaxis, adherence and cytotoxicity assay) were performed. A significant reduction of inflammatory mediators in LPS-stimulated, sevoflurane-exposed AEC was found, leading to reduced chemotaxis, neutrophil adherence and neutrophil-induced AEC killing. While iNOS2 was increased in the sevoflurane group, blocking experiments with iNOS2 inhibitor did not affect sevoflurane-induced decrease of inflammatory mediators and AEC killing. Interestingly, sevoflurane treatment also resulted in an enhanced expression of HSP-32. The data presented in the current study provide strong evidence that anaesthetic postconditioning with sevoflurane mediates cytoprotection in the respiratory compartment in an in vitro model of acute lung injury.

P38 MAPK inhibitors suppress biomarkers of hypertension end-organ damage, osteopontin and plasminogen activator inhibitor-1.

The assessment of target organ damage is important in defining the optimal treatment of hypertension and blood pressure-related cardiovascular disease. The aims of the present study were (1) to investigate candidate biomarkers of target organ damage, osteopontin (OPN) and plasminogen activator inhibitor-1 (PAI-1), in models of malignant hypertension with well characterized end-organ pathology; and (2) to evaluate the effects of chronic treatment with a p38 MAPK inhibitor. Gene expression, plasma concentrations, and renal immunohistochemical localization of OPN and PAI-1 were measured in stroke-prone spontaneously hypertensive rats on a salt-fat diet (SFD SHR-SP) and in spontaneously hypertensive rats receiving N(omega)-nitro-L-arginine methyl ester (L-NAME SHR). Plasma concentrations of OPN and PAI-1 increased significantly in SFD SHR-SP and L-NAME SHR as compared with controls, (2.5-4.5-fold for OPN and 2.0-9.0-fold for PAI-1). The plasma levels of OPN and PAI-1 were significantly correlated with the urinary excretion of albumin (p < 0.0001). Elevations in urinary albumin, plasma OPN and PAI-1 were abolished by chronic treatment (4-8 weeks) with a specific p38 MAPK inhibitor, SB-239063AN. OPN immunoreactivity was localized predominantly in the apical portion of tubule epithelium, while PAI-1 immunoreactivity was robust in glomeruli, tubules and renal artery endothelium. Treatment with the p38 MAPK inhibitor significantly reduced OPN and PAI-1 protein expression in target organs. Kidney gene expression was increased for OPN (4.9- and 7.9-fold) and PAI-1 (2.8- and 11.5-fold) in SFD SHR-SP and L-NAME SHR, respectively. In-silico pathway analysis revealed that activation of p38 MAPK was linked to OPN and PAI-1 via SPI, c-fos and c-jun; suggesting that these pathways may play an important role in p38 MAPK-dependent hypertensive renal dysfunction. The results suggest that enhanced OPN and PAI-1 expression reflects end-organ damage in hypertension and that suppression correlates with end-organ protection regardless of overt antihypertensive action.

Endothelial protective and antishock effects of a selective estrogen receptor modulator in rats.

This study investigated whether idoxifene, a selective estrogen receptor modulator (SERM), exerted protective effects against ischemia-reperfusion-induced shock. Ovariectomized rats were treated with vehicle, idoxifene, or 17beta-estradiol for 4 days. Rats were subjected to splanchnic artery occlusion (SAO) followed by reperfusion (SOA/R). In vehicle-treated rats, SAO/R resulted in hypotension, hemoconcentration, increased plasma tumor necrosis factor (TNF)-alpha levels, intestinal neutrophil accumulation, and endothelial dysfunction. 17beta-Estradiol treatment increased plasma estradiol concentration and reduced SAO/R-induced tissue injury. Idoxifene treatment had no effect on plasma estradiol concentration but reduced SAO/R-induced hemoconcentration (+8.8 +/- 1.3 vs. +14 +/- 1.3% in the vehicle group, P < 0.01), TNF-alpha production (98 +/- 3.2 vs. 214 +/- 13 pg/ml, P < 0.01), and neutrophil accumulation (0.025 +/- 0.005 vs. 0.047 +/- 0.005 U/g protein, P < 0.01). It also improved endothelial function, prolonged survival time (172 +/- 3.5 vs. 147 +/- 8 min, P < 0.01), and increased survival rate (69 vs. 23%, P < 0.01). Moreover, treatment with 17beta-estradiol or idoxifene in vivo reduced TNF-alpha-induced endothelial dysfunction in vitro. Taken together, these results demonstrated that idoxifene exerted estrogen-like, endothelial-protective, and antishock effects in ovariectomized rats, suggesting that SERMs have therapeutic potential in tissue injury resulting from ischemia-reperfusion.

Pathological, ultrastructural and immunohistochemical observations of adenoma of retinal pigment epithelium.

PURPOSE: To Study the clinical, pathological, ultrastructural and immunohistchemical characters of adenoma of the retinal pigment epithelium in order to offer evidence to diagnose this tumor. METHODS: Routine paraffin slices HE stain, histochemistry PAS and VG stain, transmission electron microscopy, and immunohistochemistry for S-100 and vimentin with LSAB method were used. RESULTS: The tumor cells were oval and cuboidal in shape. Part of the tumor had a tubular arrangement. Around the sheets of tumors cells there was a large amount of uniform red stick-like substances. The above matter represented positive in PAS stain. Most of the above matter was yellow, while less of the matter showed red in VG stain. Transmission electron microscopy showed that there were tight junctions between tumor cells. Immunohistochemistry showed positive for S-100, negative for vimentin. CONCLUSIONS: The ultrastructural and immunohistochemical characters of the adenoma of retinal pigment epithelium are consistent with the retinal pigment epithelium.

Selective estrogen receptor modulator idoxifene inhibits smooth muscle cell proliferation, enhances reendothelialization, and inhibits neointimal formation in vivo after vascular injury.

BACKGROUND: Idoxifene (ID) is a tissue-selective estrogen receptor modulator (SERM). The pharmacological profile of ID in animal studies suggests that it behaves like an estrogen receptor (ER) agonist in bone and lipid metabolism while having negligible ER activity on the reproductive system. It is unknown whether ID retains the vascular protective effects of estrogen. METHODS AND RESULTS: In cultured vascular smooth muscle cells (VSMCs), ID inhibited platelet-derived growth factor-induced DNA synthesis and mitogenesis with IC(50) values of 20.4 and 27.5 nmol/L, respectively. Treatment with ID resulted in S-phase cell cycle arrest in serum-stimulated VSMCs. ID 1 to 100 nmol/L significantly protected endothelial cells from tumor necrosis factor-alpha (TNF-alpha)-induced apoptosis in vitro. Virgin Sprague-Dawley rats ovariectomized 1 week before the study were treated with ID (1 mg x kg(-1) x d(-1)) or vehicle by gavage for 3 days before balloon denudation in carotid artery. The SMC proliferation in injured vessels was determined by immunostaining for proliferating cell nuclear antigen (PCNA). The number of PCNA-positive SMCs was reduced by 69%, 82%, and 86% in the media at days 1, 3 and 7, respectively, and by 78% in the neointima at day 7 after injury in ID- versus vehicle-treated group (P:<0.01). ID significantly enhanced reendothelialization in the injured carotid arteries as determined by Evans blue stain and immunohistochemical analysis for von Willebrand factor. In the former assay, the reendothelialized area in injured vessels was 43% in ID-treated group versus 24% in the vehicle group (P:<0.05); in the latter assay, the numbers of von Willebrand factor-positive cells per cross section increased from 24. 8 (vehicle) to 60.5 (ID) (P:<0.01) at day 14 after injury. In addition, the production of nitric oxide from excised carotid arteries was significantly higher in ID-treated than the vehicle group (8.5 versus 2.7 nmol/g, P:<0.01). Finally, ID treatment reduced neointimal area and the ratio of intima to media by 45% and 40%, respectively (P:<0.01), at day 14 after balloon angioplasty. CONCLUSIONS: The results indicate that ID beneficially modulates the balloon denudation-induced vascular injury response. Inhibition of VSMC proliferation and acceleration of endothelial recovery likely mediate this protective effect of ID.