[Current status of local treatment for multifocal / multicentric breast cancer].

The detection rate of multifocal / multicentric breast cancer (MMBC) is increasing, and the local treatment of MMBC is attracting more attention. Relevant research focuses on the selection of surgical methods, the application of radiotherapy, and the feasibility of local ablation. Currently, due to the high rate of local recurrence in breast conserving surgery, most Chinese doctors recommend mastectomy to patients with MMBC. Recent studies have shown that with the development of imaging technology, surgical techniques, accurate judgment of the resection margin, the emergence of new therapeutic drugs and the improvement of the accuracy of radiotherapy, for eligible patients with MMBC, breast conserving surgery did not increase the local recurrence rate while ensuring negative margin and cosmetic results. Whether patients with MMBC must receive adjuvant radiotherapy after mastectomy is controversial, with some evidence suggesting that MMBC may increase the risk of local recurrence and should be an important consideration for radiotherapy, and there is also evidence that the local recurrence rate of MMBC was higher regardless of the type of surgery. In general, the local treatment modality for MMBC is essentially the same as that for unifocal breast cancer, but more prospective studies are needed for further evaluation.

[Frontal pole iron deposition is associated with cognitive decline in patients with carotid atherosclerosis stenosis: a quantitative susceptibility mapping study].

Objective: To investigate the correlation between brain iron deposition and cognitive function in patients with carotid atherosclerosis stenosis (CAS) based on quantitative susceptibility mapping (QSM). Methods: This single-center prospective study was performed at the Department of Vascular Surgery, Nanjing Drum Tower Hospital from January 2022 to June 2022. Patients who met the ataxation criteria were divided into the CAS group (n=16) and the CAS with mild cognitive impairment (CAS-MCI) group (n=17) according to the Montreal Cognitive Assessment (MoCA) scores. All patients completed QSM imaging and whole-brain analyses were performed for absolute susceptibility values in cortical regions. Age, sex, education years, hypertension, and diabetes mellitus were included as covariates in all analyses. Partial correlation analyses were used to determine the correlation between bilateral CAS degrees and cortical susceptibility values. Further, mediation analyses were performed to determine whether and how cortical susceptibility values affect cognition in CAS patients. Receiver operating characteristic (ROC) curve analysis was also performed to evaluate the predictive worth of differential brain region susceptibility values for cognitive decline. Independent sample t test and Mann-Whitney U test was used to compare quantitative variables. The comparison of categorical variables was conducted using χ2 test, Fisher's exact test or Wilcoxon rank sum test. Results: A total of 33 patients were included in the study, including 16 in the CAS group and 17 in the CAS-MCI group. There were 23 males and 10 females, aged (62.8±9.0) years (range: 48 to 88 years). CAS-MCI group showed higher right CAS grades (Z=-2.037, P=0.042). Whole-brain cortical QSM analyses showed higher susceptibility values in the frontal pole ((-0.210±0.080)×10-8 vs.(-0.130±0.120)×10-8;t=-2.187, P=0.037), superior frontal gyrus ((-0.604±0.243)×10-8 vs. (-0.428±0.203)×10-8;t=-2.223,P=0.034), and temporal pole ((-0.081±0.115)×10-8 vs. (0.054±0.190)×10-8;t=-2.417, P=0.022) in CAS-MCI group compared to CAS group. The susceptibility value of the frontal pole showed a positive correlation with the right CAS grade (r=0.424, P=0.009),while a quasi-significant positive correlation with the left CAS (r=0.313, P=0.070). The susceptibility values of the frontal and temporal poles were negatively correlated with the MoCA score (frontal pole: r=-0.391, P=0.027; temporal pole: r=-0.410, P=0.020). Mediation analysis showed the effect of right CAS on cognition was fully mediated by the susceptibility value of the frontal pole. The ROC curve revealed that the area under the curve of using hypertension combined with the susceptibility value of the frontal pole to predict cognitive decline was 0.882 (95% CI:0.763 to 0.989) with 82% of sensitivity and 83% of specificity. Conclusions: Multiple cortical regions show iron deposition in CAS-MCI patients. Right CAS plays an important role in cognitive decline, frontal pole iron deposition mediates the effect of right CAS on cognitive function. Quantified frontal pole susceptibility is useful for the diagnosis of cognitive decline in patients with CAS.

Radiation-induced cancer after treatment for nasopharyngeal carcinoma: a study from a high prevalence area.

BACKGROUND: Radiation-induced cancer (RIC) is a late complication in patients who have been treated for nasopharyngeal carcinoma (NPC). The comparison of index anatomic location, index histological type, and survival of RIC in patients with NPC after different radiotherapy modalities (intensity-modulated radiotherapy [IMRT], 3-dimensional conformal radiotherapy [3D-CRT], and conventional 2D radiotherapy) is currently unavailable. METHODOLOGY: A total of 38,565 patients with NPC who received curative-intent radiotherapy at Sun Yat-sen University Cancer Center between January 1986 and December 2017 were reviewed. A total of 141 patients who developed RIC and fulfilled the study criteria were included. Categorical variables were compared by the chi-square test or Fisher's exact test. Kaplan-Meier curves were used to evaluate overall survival. Cox proportional hazards models were used to examine the independent significance of RIC treatment. RESULTS: Among IMRT, 3D-CRT, and conventional 2D radiotherapy, the incidence of mandible RIC was higher in patients who received 3D-CRT (0.07%) than in those who received IMRT (0%). The proportion of mandible RICs was higher in patients who received 3D-CRT (16.667%) than in those who received IMRT (0%) and conventional 2D radiotherapy (3.529%). Regarding the histological type, the incidence of squamous cell carcinoma (SCC) was higher in patients who received conventional 2D radiotherapy (0.266%) than in those who received 3D-CRT (0.175%); patients who received IMRT had a higher proportion of SCC than those who received 3D-CRT/conventional 2D radiotherapy (86.4% vs. 41.7% vs. 74.2%); the incidence of sarcoma was higher in patients who received 3D-CRT (0.175%) than in those who received IMRT (0.025%); and the proportion of sarcoma was higher in patients who received 3D-CRT (41.667%) than in those who received IMRT (6.818%) and conventional 2D radiotherapy (17.647%). Patients who received surgery for RICs had better survival than those who received no surgery (64.49 vs. 12.42 months). In the univariate and multivariate analyses, surgery was an independent prognostic factor for overall survival. CONCLUSIONS: Our results have implications for long-term follow-up of RIC, multidisciplinary management, and patient counseling of RIC after nasopharyngeal carcinoma treatment by treating clinicians.

[The characteristics and citation analysis of the publications in the National Medical Journal of China from 2017 to 2019].

Objective: To analyze the characteristics and citation of National Medical Journal of China (NMJC) from 2017 to 2019, and provide reference for the development of the journal. Methods: All the literature published in NMJC during the period 2017 to 2019 was selected as the research objects, and the citation frequency data in Chinese core periodicals of science and technology from January 2018 to December 2021 were obtained through Institute of Scientific and Technical Information of China. The main indicators included the citation rate of published articles, average citation frequency of articles, citation status of individual papers, high citation authors and their affiliations from 2017 to 2019. Results: A total of 2 694 articles were published in 21 columns of NMJC from 2017 to 2019. The total number of published pages was 11 689, and the average number of articles was 4.34 pages. The total number of cited papers was 1 849, accounting for 68.63%. Among them, 845 papers were not cited, accounting for 31.37%. The total citation times was 6 578, with an average citation of 2.44 times. The highest citation frequency of a single paper was 217 times. A total of 54.27% articles obtained fund support, and the cited rate (72.78%) was slightly higher than that of articles without fund support (63.72%). Standard and specification articles were cited 1 817 times, with a citation rate of 96.67%, and 66 articles were cited more than 10 times. The columns with more than 30 articles but all cited less than 1 time included case report and difficult case analysis. The first author was from 31 provinces (autonomous regions, municipalities directly under the Central Government) in China. There were 21 corresponding authors whose papers have been cited more than 30 times, and 18 of them were from major hospitals and science academies in Beijing. Conclusions: NMJC has a wide coverage of contributions and strong academic influence during the period 2017 to 2019. The cited frequency of standard and specification articles is high, while case report and difficult case analysis evaluation column articles have very low cited frequencies. Therefore, NMJC should further adjust column setting, improve the academic quality, reduce the number of zero cited papers, and thus enhance the influence of the magazine.

[Progress and prospect of clinical application of anti-rabies virus monoclonal antibody preparation].

Rabies is a severe infectious disease caused by the rabies virus, which seriously damages the central nervous system. Once it occurs, the fatality rate is close to 100%. The World Health Organization's position paper on rabies vaccines recognizes that rabies immunoglobulin (RIG) should be used for post-exposure prophylaxis (PEP) in all category Ⅲ exposure for the first time, as well as in category Ⅱ exposure that suffer from severe immune deficiency, long-term massive use of immunosuppressants, and head and face exposure. The anti-rabies virus monoclonal antibody has high purity and specific activity, can be produced on a sustainable scale, and has no risk of blood source virus contamination. Preclinical pharmacodynamic studies and clinical trial results of the anti-rabies virus monoclonal antibody preparation have confirmed that the preparation has a broad-spectrum neutralization effect on the rabies virus. Additionally, its combined application with the vaccine has little impact on the active immunity of the vaccine. Therefore, the anti-rabies virus monoclonal antibody preparation shows great potential for clinical application in PEP.

[Treatment and prognosis analysis of 488 patients with FIGO 2018 stage â ¢c squamous cervical cancer].

Objective: To analyze the treatment and prognosis of patients with International Federation of Gynecology and Obstetrics (FIGO) 2018 stage Ⅲc cervical squamous cell carcinoma. Methods: A total of 488 patients at Zhejiang Cancer Hospital between May, 2013 to May, 2015 were enrolled. The clinical characteristics and prognosis were compared according to the treatment mode (surgery combined with postoperative chemoradiotherapy vs radical concurrent chemoradiotherapy). The median follow-up time was (96±12) months ( range time from 84 to 108 months). Results: (1) The data were divided into surgery combined with chemoradiotherapy group (surgery group) and concurrent chemoradiotherapy group (radiotherapy group), including 324 cases in the surgery group and 164 cases in the radiotherapy group. There were significant differences in Eastern Cooperation Oncology Group (ECOG) score, FIGO 2018 stage, large tumors (≥4 cm), total treatment time and total treatment cost between the two groups (all P<0.01). (2) Prognosis: ① for stage Ⅲc1 patients, there were 299 patients in the surgery group with 250 patients survived (83.6%). In the radiotherapy group, 74 patients survived (52.9%). The difference of survival rates between the two groups was statistically significant (P<0.001). For stage Ⅲc2 patients, there were 25 patients in surgery group with 12 patients survived (48.0%). In the radiotherapy group, there were 24 cases, 8 cases survived, the survival rate was 33.3%. There was no significant difference between the two groups (P=0.296). ② For patients with large tumors (≥4 cm) in the surgery group, there were 138 patients in the Ⅲc1 group with 112 patients survived (81.2%); in the radiotherapy group, there were 108 cases with 56 cases survived (51.9%). The difference between the two groups was statistically significant (P<0.001). Large tumors accounted for 46.2% (138/299) vs 77.1% (108/140) in the surgery group and radiotherapy group. The difference between the two groups was statistically significant (P<0.001). Further stratified analysis, a total of 46 patients with large tumors of FIGO 2009 stage Ⅱb in the radiotherapy group were extracted, and the survival rate was 67.4%, there was no significant difference compared with the surgery group (81.2%; P=0.052). ③ Of 126 patients with common iliac lymph node, 83 patients survived, with a survival rate of 65.9% (83/126). In the surgery group, 48 patients survived and 17 died, with a survival rate of 73.8%. In the radiotherapy group, 35 patients survived and 26 died, with a survival rate of 57.4%. There were no significant difference between the two groups (P=0.051). (3) Side effects: the incidence of lymphocysts and intestinal obstruction in the surgery group were higher than those in the radiotherapy group, and the incidence of ureteral obstruction and acute and chronic radiation enteritis were lower than those in the radiotherapy group, and there were statistically significant differences (all P<0.01). Conclusions: For stage Ⅲc1 patients who meet the conditions for surgery, surgery combined with postoperative adjuvant chemoradiotherapy and radical chemoradiotherapy are acceptable treatment methods regardless of pelvic lymph node metastasis (excluding common iliac lymph node metastasis), even if the maximum diameter of the tumor is ≥4 cm. For patients with common iliac lymph node metastasis and stage Ⅲc2, there is no significant difference in the survival rate between the two treatment methods. Based on the duration of treatment and economic considerations, concurrent chemoradiotherapy is recommended for the patients.

[Regional analysis of high risk factors of hypertensive disorders in pregnancy with organ or system impairment].

Objective: To explore the influencing factors of pregnancy-induced hypertensive disorders in pregnancy (HDP) with organ or system impairment in pregnant women, and to analyze and compare the differences of HDP subtypes in different regions of China. Methods: A total of 27 680 pregnant women with HDP with complete data from 161 hospitals in 24 provinces, autonomous regions and municipalities were retrospectively collected from January 1, 2018 to December 31, 2018. According to their clinical manifestations, they were divided into hypertension group [a total of 10 308 cases, including 8 250 cases of gestational hypertension (GH), 2 058 cases of chronic hypertension during pregnancy] and hypertension with organ or system impairment group [17 372 cases, including 14 590 cases of pre-eclampsia (PE), 137 cases of eclampsia, 2 645 cases of chronic hypertension with PE]. The subtype distribution of HDP in East China (6 136 cases), North China (4 821 cases), Central China (3 502 cases), South China (8 371 cases), Northeast China (1 456 cases), Southwest China (2 158 cases) and Northwest China (1 236 cases) were analyzed. By comparing the differences of HDP subtypes and related risk factors in different regions, regional analysis of the risk factors of HDP pregnant women with organ or system impairment was conducted. Results: (1) The proportions of HDP pregnant women with organ or system impairment in Northeast China (79.05%, 1 151/1 456), Central China (68.42%, 2 396/3 502) and Northwest China (69.34%, 857/1 236) were higher than the national average (62.76%, 17 372/27 680); the proportions in North China (59.18%, 2 853/4 821), East China (60.85%, 3 734/6 136) and South China (59.56%, 4 986/8 371) were lower than the national average, and the differences were statistically significant (all P<0.05). (2) Univariate analysis showed that the proportions of primiparas, non-Han, non-urban household registration, irregular prenatal examination and PE history in the hypertension with organ or system impairment group were higher than those in the hypertension group, and the differences were statistically significant (all P<0.05). Multivariate logistic regression analysis showed that primiparas, non-Han, non-urban household registration, irregular prenatal examination and PE history were independent risk factors for HDP pregnant women with organ or system impairment (all P<0.05). (3) Primipara: the rates of primipara in Northeast China, North China and Southwest China were higher than the national average level, while those in South China, Central China and Northwest China were lower than the national average level. Non-Han nationality: the rates of non-Han nationality in Northeast China, North China and Northwest China were higher than the national average, while those in East China, South China and Central China were lower than the national average. Non-urban household registration: the rates of non-urban household registration in Northeast China, North China, and Southwest China were lower than the national average, while those in East China, Central China were higher than the national average. Irregular prenatal examination: the rates of irregular prenatal examination in North China, South China and Southwest regions were lower than the national average level, while those in Northeast China, Central China and Northwest China were higher than the national average level. History of PE: the incidence rates of PE in Northeast China, North China, South China and Southwest China were lower than the national average level, while those in Central China and Northwest China were higher than the national average level. Conclusions: Primiparas, non-Han, non-urban household registration, irregular prenatal examination, and PE history are risk factors for HDP pregnant women with organ or system impairment. Patients in Northeast, Central and Northwest China have more risk factors, and are more likely to be accompanied by organ or system function damage. It is important to strengthen the management of pregnant women and reduce the occurrence of HDP.

[Surgical treatment strategy of pulmonary artery sling: a series of 110 cases].

Objective: To examine the effect of surgical treatment in children with pulmonary artery sling and the surgical treatment strategy. Methods: Relevant data of 110 children with pulmonary artery sling admitted to the Department of Cardiac Surgery, Children's Hospital Affiliated to Shandong University from February 2017 to July 2022 were retrospectively analyzed. There were 55 males and 55 females, aging (M(IQR)) 9.0 (10.6) months (range: 1 to 96 months). The weight was 7.8 (3.5) kg (range: 2.5 to 25.0 kg). Of the 110 patients, 108 had different degrees of tracheal stenosis and 2 had normal trachea. Left pulmonary artery transplantation and tracheoplasty were performed in 78 patients. Left pulmonary artery transplantation was performed in 30 patients (11 in our hospital and 19 in other hospitals) due to the lack of an early tracheoplasty technique, in which 24 patients needed stage Ⅱ tracheoplasty due to obvious respiratory symptoms and limited activity endurance, and 6 cases did not intervene. Two children with normal trachea only underwent left pulmonary artery transplantation. Results: Among the 78 children who underwent surgery in the same period, 70 cases recovered smoothly after surgery, of whom respiratory symptoms were significantly reduced or disappeared during the 1 to 65 months follow-up, with similar activity endurance to normal children of the same age. Eight cases died, including 4 cases of postoperative multi-drug resistant bacteria infection, died from tracheal anastomotic opening or septic shock, 1 cases with severe congenital heart disease died from postoperative low cardiac output syndrome difficult to correct, 1 case died from blood pressure could not be maintained due to the compressed left pulmonary artery after transplantation, 2 cases of postoperative digestive system diseases (adhesive intestinal obstruction, gastrointestinal bleeding, etc.). The 24 patients in the staging group were followed for 1 to 84 months. All patients needed stage Ⅱ tracheoplasty due to respiratory symptoms and decreased endurance to activity. Eight cases of the non-intervention tracheal group were successfully separated from the ventilator, cured and discharged in a short period of time. Conclusions: Most children with pulmonary artery sling have tracheal stenosis. Children with low degree of tracheal stenosis and inconspicuous respiratory symptoms can only undergo left pulmonary artery transplantation by lateral thoracotomy. For patients combined with severe tracheal stenosis or obvious respiratory symptoms, a simultaneous left pulmonary artery transplantat and tracheoplasty is recommended.

[Treatment strategy of congenital tracheal stenosis associated with non-vascular ring cardiac malformations].

Objective: To examine the treatment strategy of congenital tracheal stenosis associated with non-vascular ring cardiac malformations. Methods: This is a retrospective case series. Clinic data from 24 children with tracheal stenosis who underwent surgical treatment in the Department of Cardiac Surgery, Children's Hospital Affiliated to Shandong University from February 2017 to March 2023 were retrospectively collected. There were 16 males and 8 females, aged (M(IQR)) 6.5 (19.6) months (range: 2.2 to 66.3 months) and weighted 5.95 (4.76) kg (range: 3.2 to 20.0 kg). All patients had obvious respiratory symptoms. Eighteen patients underwent cardiac malformation correction and tracheoplasty at the same time (simultaneous group). Six patients in the staged operation group were treated with cardiac malformation correction in the first stage operation and tracheoplasty in the second stage operation due to missed diagnosis or delayed diagnosis of tracheal stenosis or no condition for tracheoplasty. Slide tracheoplasty was used to correct tracheal stenosis in both groups. The recovery of the children was followed. Wilcoxon sign rank test was used for comparison between the two groups. Results: There was no death during the perioperative period and hospitalization. In the simultaneous group, 1 case with delayed chest closure underwent bedside chest closure after 52 hours, 2 cases were intubated again after operation, and 1 case was implanted with an endotracheal stent. The duration of mechanical ventilation was 40.5 (39.6) hours (range: 19.0 to 438.8 hours). In the staged group, there was 1 case of re-intubation after operation, combined with left vocal cord paralysis and respiratory multidrug-resistant bacterial infection (Acinetobacter baumanii). One patient underwent 3 times of bronchoscopic balloon dilatation of the right middle bronchus, and heart rate returned to normal range. The duration of mechanical ventilation was 19.0 (21.4) hours (range: 17.1 to 96.7 hours). During follow-up, a patient in the simultaneous group was prone to respiratory infection and had good exercise tolerance, 1 patient in the staged group still had sputum stridor in the throat 3 months after the operation, and symptoms improved significantly 6 months after the operation. The other children didn't have obvious respiratory symptoms. Conclusions: The diagnosis of tracheal stenosis may be delayed or missed when tracheal stenosis is complicated by non-vascular ring cardiac malformations. One-stage correction of tracheal stenosis and cardiac malformation can achieve a good outcome.

[Evaluation of right ventricular function using two-dimensional speckle tracking echocardiography and analysis of the risk factors for right ventricular dysfunction in patients with silicosis].

Objective: To evaluate the right ventricular function using two-dimensional speckle tracking echocardiography (2-D STE) and analyze the associated risk factors of right ventricular dysfunction in patients with silicosis. Methods: All 104 patients with silicosis treated in the Department of Occupational Medicine and Toxicology in Beijing Chao-Yang Hospital, Capital Medical University from May 2021 to September 2022 were enrolled in this study in October 2022. The clinical information of patients such as general data, arterial blood gas analysis and pulmonary function test were collected. The right ventricular function of patients was evaluated by 2-D STE-derived right ventricular free wall longitudinal strain (RVFWLS) and conventional echocardiographic-derived parameters, including right ventricular fractional area change (RVFAC), tricuspid annular plane systolic excursion (TAPSE) and doppler tissue imaging-derived tricuspid lateral annular systolic velocity (S'), respectively. Based on their RVFWLS, the patients were divided into right ventricular dysfunction group and normal right ventricular function group. Risk factors for right ventricular dysfunction in patients with silicosis were analyzed using binary logistic regression analysis. Results: A total of 104 silicosis patients were enrolled, with aneverage age (65.52±11.18) years old, among whom including 57 cases diagnosed with stage Ⅰ/Ⅱ silicosis and 47 cases diagnosed with stage Ⅲ silicosis. 26 (25.00%) patients concurrent right ventricular dysfunction. The abnormal rates of RVFAC, TAPSE and S' in patients were 16.35% (17 cases), 21.15% (22 cases) and 6.73% (7 cases), respectively. The RVFAC and TAPSE in right ventricular dysfunction group were lower than those in normal right ventricular function group, and the incidence of pulmonary arterial systolic pressure ≥36 mmHg was higher than that in normal right ventricular function group (P<0.05). Logistic regression analysis showed that arterial partial pressure of oxygen (OR=0.932, 95%CI: 0.885-0.981, P=0.007) was the protective factor, and the forced expiratory volume in 1 second (FEV(1)) /forced vital capacity (FVC) ratio<70% (OR=5.484, 95%CI: 1.049-28.662, P=0.044) and stage Ⅲ silicosis (OR=6.343, 95%CI: 1.698-23.697, P=0.007) were the risk factors for silicosis patients concurrent right ventricular dysfunction. Conclusion: The incidence of right ventricular dysfunction is higher in patients with stage Ⅲ silicosis than that in patients with stage Ⅰ/Ⅱ silicosis. Using 2-D STE can help the early detection of silicosis with right ventricular dysfunction. Hypoxemia, airflow limitation and the stage Ⅲ silicosis are the risk factors for silicosis patients concurrent right ventricular dysfunction.

[Efficacy and prognostic analysis of 125I brathytherapy combined with chemotherapy for pediatric parameningeal rhabdomyosarcoma].

Objective: To analyze the efficacy and prognostic factors in children with parameningeal rhabdomyosarcoma (PMRMS) treated by 125I brachytherapy combined with chemotherapy. Methods: A retrospective analysis of the clinical data of 33 pediatric patients treated with 125I brachytherapy combined with chemotherapy in Peking University Stomatological Hospital from July 2013 to October 2018 was carried out to analyze the efficacy and prognostic factors. Results: Among the 33 patients, 19 were males and 14 were females; the median age was 4 years old (1-12 years old). There were 17 cases with embryonic type, 9 cases with alveolar type, and 7 with undifferentiated type; 26 cases with original PMRMS, and 7 cases with recurrent PMRMS. The tumors occurred in subtemporal-mastoid area in 15 patients, while nasopalatine-paranasal area in 6 cases, and parapharyngeal-submandibular area in 12 cases. There were 28 patients in IRS Ⅲ, and 5 patients in IRS Ⅳ. As for the risk level, 28 cases were in the middle-risk group and 5 cases in the high-risk group. The median follow-up time was 52 months. The 1, 3, and 5-year local control rates were 87.9%, 58.6%, and 49.9%, and the 1, 3, and 5-year survival rates were 93.8%, 60.5%, and 47.5%, respectively. The 5-year local control rate and 5-year survival rate of 12 patients with the tumor in the parapharyngeal-submandibular area were 91.7% and 100%, respectively. The 5-year local control rate and 5-year survival rate of the 6 patients with tumor in the nasopalatine-paranasal area were both 83.3%. The 3-year local control rate and 3-year survival rate of the 15 patients with tumor in the subtemporal-mastoid area were 17.5% and 21.4%. The multivariate survival analysis using Cox proportional risk regression model showed that the tumor located in the subtemporal-mastoid area was an independent risk factor affecting the 5-year overall survival rate (HR=38.40, 95%CI: 4.87-302.52, P=0.001). Within 3 months after 125I seed implantation, the incidence of acute radiotherapy adverse reactions in all patients was 84.8% (28/33). Twenty-one patients (63.6%) had a grade 1 acute radiotherapy reaction, and 7 cases (21.2%) had a grade 2 acute radiotherapy reaction. No acute radiotherapy adverse reactions of grade 3 or 4 occurred. Three months after 125I seed implantation, the adverse reactions were significantly alleviated, and no adverse reactions of grade 3 or above such as skin ulcer or salivary gland fibrosis occurred, and no serious cranio-maxillofacial deformities occurred. Conclusions: 125I seed brachytherapy combined with chemotherapy has a definite clinical effect in the treatment of children with parameningeal rhabdomyosarcoma. The prognosis of rhabdomyosarcoma in the parapharyngeal-submandibular area and nasopalatine-paranasal area is better than that in the subtemporal-mastoid area.

[Multidisciplinary regenerative treatment and mechanisms for rescuing a severe calciphylaxis patient with human amnion-derived mesenchymal stem cells].

Calciphylaxis is a rare disease with severe pain and high-mortality due to cutaneous ischemic necrosis and infection that currently lacks proved effective therapies. The occurrence of calciphylaxis in end stage kidney disease (ESKD) patients is known as calcific uremic arteriolopathy (CUA), which is characterized histologically by dermal microvessel calcification, intimal fibroplasia and microthrombosis. Here we innovatively treated a severe CUA patient with human amnion-derived mesenchymal stem cells (hAMSCs). A 34-year-old uremic woman was presented with progressive, painful malodorous ulcers in buttocks and mummified lower limbs. Skin pathological features supported the diagnosis of calciphylaxis. The patient was refractory to conventional multidisciplinary symptomatic therapies. With the approval of our hospital ethics committee, she was treated with hAMSCs including intravenous and local intramuscular injection, and external application of hAMSC culture supernatant to the wound area. During 15-month follow-up, the patient had regeneration of skin and soft tissues, with improved blood biochemical, inflammatory, mineral and bone metabolic indices and immunoregulation effects. After 15-month hAMSC treatment, the score of pain visual analog scale (VAS) decreased from 10 to 0, Bates-Jensen wound assessment tool (BWAT) score decreased from 65 to 13, and wound-quality of life (Wound-QoL) questionnaire score decreased from 68 to 0. We propose that hAMSC treatment is promising for CUA patients. The therapy is potentially involved in the multiple beneficial effects of inhibiting vascular calcification, stimulating angiogenesis and myogenesis, modulating adverse inflammatory and immunologic responses, promoting re-epithelialization and restoring skin integrity.

[Development of a Ranking Tool for Scientificity, Transparency and Applicability of Clinical Practice Guidelines].

Objective: To address the limitations of existing methods and tools for evaluating clinical practice guidelines, we aimed to develop a comprehensive instrument focusing on the three main dimensions of guideline development: scientificity, transparency, applicability. We will use it to rank the guidelines according to the scores. We abbreviated it as STAR, and its reliability, validity and usability were also tested. Methods: A multidisciplinary expert working group was set up, including methodologists, statisticians, journal editors, medical professionals, and others. Scoping review, Delphi methods and hierarchical analysis were used to determine the final checklist of STAR. Results: The new instrument contained 11 domains and 39 items. Intrinsic reliability of each domain was indicated by Cronbach's α coefficient, with a average value of 0.646. The Cohen's kappa coefficients for methodological evaluators and clinical evaluators were 0.783 and 0.618. The overall content validity index was 0.905. The R2 for the criterion validity analysis was 0.76. The average score for usability of the items was 4.6, and the mean time spent to evaluate each guideline was 20 minutes. Conclusion: The instrument has good reliability, validity and evaluating efficiency, and can be used for evaluating and ranking guidelines more comprehensively.

[Nasopharyngeal carcinoma with non-squamous immunophenotype: a clinicopathological analysis of 23 cases].

Objective: To investigate the pathological subtypes and clinicopathological characteristics of the non-squamous immunophenotype nasopharyngeal carcinoma (NSNPC). Methods: The clinicopathological features of the non-squamous immunophenotype nasopharyngeal carcinoma diagnosed between 2011 and 2019 at the First Affiliated Hospital of Zhengzhou University were analyzed using hematoxylin and eosin staining, immunohistochemistry, in situ hybridization, transmission electron microscopy and PCR gene rearrangement. Follow-up data were also collected. Results: There were 14 males and 9 females with a median age of 46 years (ranging from 16 to 76 years) with an average age of 45 years. Microscopically, patterns were similar to the classic nasopharyngeal carcinoma. Immunohistochemistry showed that most NSNPC cases expressed low molecular weight keratin (CK8/18, CK8 and CKL) and expressed pathway proteins in a low level (EGFR, PI3K, p-AKT and p-mTOR), which had significant difference from classic nasopharyngeal carcinoma group (P<0.05). Other proteins including CK5/6, CKpan, CK7, Syn, CD56, CgA, SOX-10, AKT, mTOR, Notch, STAT3 and p-STAT3 showed no statistical difference between the two groups. Pathogen detection showed that EBER was positive (18/23, 78.3%) and HPV positive(2/23, 8.7%)which were HPV35 and HPV38. The cancer suppressor gene BLU was highly expressed in NSNPC; RASSF1 and Rbms3 were less expressed in NSNPC, in line with classic NPC. As a whole, NSNPC was characterized by ultrastructures of low-differentiated squamous cell carcinoma. Compared with classic nasopharyngeal carcinoma, NSNPC had a lower recurrence rate and earlier clinical stage(P<0.05),but there was no significant correlation with age, sex, distant metastasis and death (P>0.05). Conclusions: The histological morphology, etiology and gene changes of NSNPC are similar to those of classical nasopharyngeal carcinoma and ultrastructural findings show that NSNPC still belongs to undifferentiated type in non-keratinized squamous cell carcinoma. The malignant degree of NSNPC is low and the prognosis is good.

[Effect of macrophage-derived exosomes on promoting hepatic stellate cell activation and platelet-derived growth factor expression].

Objective: To explore the effect of macrophage-derived exosomes on the activation of hepatic stellate cells and its possible mechanism. Methods: Differential ultracentrifugation was used to extract macrophage exosomes. The exosomes were co-cultured with the mouse hepatic stellate cell line JS1, and a control group was established with phosphate buffered saline (PBS). Cell immunofluorescence was used to observe the expressional conditions of F-actin. Cell counting kit-8 (CCK8) was used to detect the survival rate of JS1 cells in the two groups. The activation indices of JS1 cells [collagen type Ⅰ (Col Ⅰ) and α-smooth muscle actin (α-SMA)] and its key signal pathway activation index expression level [transforming growth factor (TGF)-ß1/Smads, platelet-derived growth factor (PDGF)] in the two groups were determined using Western blot and RT-PCR. Data comparison between two groups was performed using an independent sample t-test. Results: The membrane structure of exosomes was clearly observed by transmission electron microscopy. The expression of exosome marker proteins CD63 and CD81 was positive, suggesting that exosomes were successfully extracted. Exosomes were co-cultured with JS1 cells. Compared with the PBS control group, there was no statistically significant difference in the proliferation rate of JS1 cells in the exosomes group (P＞0.05). The expression of F-actin was significantly increased in the exosome group. The mRNA and protein expression levels of α-SMA and ColⅠwere significantly increased in exosome group JS1 cells (all P＜0.05). The mRNA relative expression levels of α-SMA in PBS and exosome group were 0.25±0.07 and 1.43±0.19, respectively, while that of ColⅠ was 1.03±0.04 and 1.57±0.06, respectively. The mRNA and protein expressions of PDGF were significantly increased in exosome group JS1 cells (P＜0.05). The mRNA relative expression levels of PDGF in the PBS group and exosome group were 0.27±0.04 and 1.65±0.12, respectively. There were no statistically significant differences in the mRNA and protein expressions of TGF-ß1, Smad2 and Smad3 between the two groups (P＞0.05). Conclusion: Macrophage-derived exosomes significantly promote the activation of hepatic stellate cells. JS1 cells may be the underlying mechanism for the up-regulation of PDGF expression.

[Comparison of follow-up treatment regimens for colorectal cancer liver metastases without objective response to neoadjuvant chemotherapy: direct surgery or surgery after second-line chemotherapy].

Objective: To compare the effect of direct surgery or surgery after second-line chemotherapy for colorectal cancer patients with liver metastases who did not achieve objective remission after neoadjuvant chemotherapy. Methods: A retrospective case cohort study was used. The clinical and pathological data of 107 patients with colorectal cancer liver metastases who did not achieve objective response to neoadjuvant chemotherapy at Department of Hepatobiliary Surgery,Cancer Hospital,Chinese Academy of Medical Sciences from December 2008 to December 2016 were retrospectively collected. There were 71 males and 36 females, median age was 57 years (range: 28 to 79 years). According to the different treatment regimens after neoadjuvant chemotherapy,107 cases were divided into a direct surgery group (direct group,n=65) and an operation after receiving second-line chemotherapy group (second-line group,n=42). The propensity score matching(PSM) of the Logistic regression model was used to match the bilobar distribution of liver metastases and the number of first-line chemotherapy cycles in the two groups of patients. The caliper value was set to 0.10 and the matching ratio was 1∶2. T test, Mann-Whitney U test, χ2 test or Fisher's exat test was used to analyzed the data between the tuo groups, respectively. Survival analysis design was used to investigate the difference in prognosis between the two groups of patients. Results: The follow-up time(M(IQR)) was 56.3(34.3) months (range: 2.1 to 95.0 months),and all patients were followed up. After PSM,there were 28 cases in the direct group and 42 cases in the second-line group, there were no significant differences in whether R0 resection was feasible,blood loss,blood transfusion,postoperative complications and postoperative hospital stay between the two groups (all P>0.05). The 1,3,and 5-year progression-free survival(PFS) rates of the direct group were 40.0%,16.5%,and 11.0%,and the 1,3,and 5-year overall survival(OS) rates were 98.5%,61.2%,and 41.4%,respectively, the second-line group 1,3,5 years PFS rates were 35.7%,14.3%,14.3%,1,3,5-year OS rate were 95.2%,55.1%,44.4%,respectively. The median PFS time of the direct group and the second-line group was 8.5 months and 7.5 months,respectively,and the difference was not statistically significant (P=0.826). The median OS time of the direct group and the second-line group were 33.8 months and 46.9 months,respectively. The difference was not statistically significant(P=0.646).The median PFS time of the direct group and second-line chemotherapy complete remission and partial remission group(CR/PR group) was 10.2 months and 9.1 months,respectively,and the difference was not statistically significant(P=0.669). The median OS time of the direct group and the second-line CR/PR group was 51.0 months and 46.9 months,respectively,and the difference was not statistically significant(P=0.427). The results of survival analysis suggested that major liver resection was an independent prognosis factor for PFS (HR=1.809,95%CI: 1.067 to 3.067,P=0.028) and OS(HR=2.751,95%CI: 1.317 to 5.747,P=0.007). Second-line chemotherapy was not an independent prognostic factor for PFS (HR=0.945, 95%CI:0.570 to 1.567,P=0.828) and OS (HR=0.866,95%CI: 0.468 to 1.602,P=0.646). Conclusions: There is no significant difference in the short-term outcome and long-term prognosis between direct surgery patients and second-line chemotherapy followed by surgery. Second-line chemotherapy is not an independent prognostic factor for colorectal cancer liver metastases patients who fail to achieve objective response after neoadjuvant chemotherapy.

[Surgical tracheoplasty for children with congenital tracheal stenosis undergoing previous balloon dilatation or tracheal metal stent placement: a series of 9 cases].

Objective: To examine the outcomes of Slide tracheoplasty for the children with severe congenital tracheal stenosis received previous repeated balloon dilatation or metal stent placement under endoscopy. Methods: A retrospective study was conducted in 9 children with congenital tracheal stenosis undergoing previous interventional therapy under tracheoscopy and later received Slide tracheoplasty due to obvious respiratory symptoms at Department of Cardiac Surgery, Qilu Children's Hospital of Shandong University between February 2017 and July 2021. There were 7 males and 2 females with a median age at operation of 72.4 months (range: 13.3 to 98.9 months), and the median weight was 19.0 kg (range: 9.0 to 33.0 kg). Among the 9 patients, 2 patients began to receive repeated balloon dilatation (more than 3 times) 17.8 and 51.8 months ago respectively. One patient received metal stents placement into the trachea for 4 days and the other 6 children for median 56.8 months (range: 21.6 to 74.2 months). Complete tracheal cartilage rings and long segmental stenosis were present. in all 9 children. Operative details and outcome measures, including the need for endoscopic airway intervention and mortality, were collected. Results: Slide tracheoplasty was performed in all cases. Two patients with repeated balloon dilatation had different thickness of tracheal wall, local scar hyperplasia and irregular lumen. Among them, 1 case had obvious local calcification of tracheal wall, which was difficult to suture. The metal stent in one patient with short time of placement was completely removed. However, only part of the metal stents could be removed due to the long placement time in the other 6 cases. There was no operative death in the 9 children. The median postoperative tracheal intubation time was 25.3 hours (range: 17.4 to 74.5 hours). A silicone stent was placed in the trachea of 1 child due to obvious respiratory symptoms. Follow-up of median 11 months (range: 1 to 23 months) showed that no death occurred after discharge and all children had basically normal activity tolerance with no obvious respiratory symptoms. Conclusions: Slide tracheoplasty is feasible for children undergoing prior balloon dilatation or metal stents placement. Previously repeated balloon dilatation or metal stent placement under endoscopy increased the difficulty of slide tracheoplasty, the metal stent could not be completely removed after a long time.

[Cardiovascular events and risk factors in hematological neoplasms patients treated with anthracyclines].

Objective: To explore the incidence and risk factors of cardiovascular events in hematological neoplasms patients treated with anthracyclines in the real world. Methods: A total of 408 patients with lymphoma and leukemia, who were treated with anthracyclines during hospitalization in the First Affiliated Hospital of Dalian Medical University from January 1, 2018 to July 31, 2021, were included in this retrospective study. Patients were divided into cardiovascular event group (n=74) and non-cardiovascular event group (n=334). The primary endpoint was cardiovascular events (arrhythmia, heart failure, acute myocardial infarction etc.) after anthracyclines therapy. The secondary endpoint was all-cause mortality, cardiovascular-cause death, discontinued chemotherapy due to cardiovascular events. Multivariate regression analysis was used to investigate the risk factors of cardiovascular events. Kaplan-Meier was performed to calculate the incidence of all-cause mortality. Results: The mean age was (55.6±14.9) years, and there were 227 male patients (55.6%) in this cohort. The median follow-up time was 45 months. During follow-up, cardiovascular adverse events occurred in 74 patients (18.1%), including 45 heart failure (38 were heart failure with preserved ejection fraction), 30 arrhythmia, 4 acute myocardial infarction and 2 myocarditis/pericarditis. Multivariate regression analysis showed age (OR=1.024, 95%CI 1.003-1.045, P=0.027) and history of hypertension over 10 years (OR=2.328, 95%CI 1.055-5.134, P=0.036) were independent risk factors for the cardiovascular events. Kaplan-Meier survival curve showed mortality was significantly higher in cardiovascular event group than in non-cardiovascular event group (47.3% vs. 26.6%, P=0.001). In the cardiovascular event group, chemotherapy was discontinued in 9 cases (12.2%) due to cardiovascular events and cardiovascular death occurred in 7 cases (9.5%). Conclusions: Although heart failure is the main cardiovascular event in lymphoma and leukemia patients post anthracyclines therapy, other cardiovascular events especially arrhythmias are also common. The presence of cardiovascular events is associated with higher risk of all-cause mortality in these patients. Age and long-term hypertension are independent risk factors for cardiovascular events in lymphoma and leukemia patients after anthracyclines treatment.

Adult skin acute stress responses to short-term environmental and internal aggression from exposome factors.

Exposome factors that lead to stressed skin can be defined as any disturbance to homeostasis from environmental (meteorological factors, solar radiation, pollution or tobacco smoke) and/or internal exposure (unhealthy diet, hormonal variations, lack of sleep, psychosocial stress). The clinical and biological impact of chronic exposome effects on skin functions has been extensively reviewed, whereas there is a paucity of information on the impact of short-term acute exposure. Acute stress, which would typically last minutes to hours (and generally no more than a week), provokes a transient but robust neuroendocrine-immune and tissue remodelling response in the skin and can alter the skin barrier. Firstly, we provide an overview of the biological effects of various acute stressors on six key skin functions, namely the skin physical barrier, pigmentation, defences (antioxidant, immune cell-mediated, microbial and microbiome maintenance), structure (extracellular matrix and appendages), neuroendocrine and thermoregulation functions. Secondly, we describe the biological and clinical effects on adult skin from individual exposome factors that elicit an acute stress response and their consequences in skin health maintenance. Clinical manifestations of acutely stressed skin may include dry skin that might accentuate fine lines, oily skin, sensitive skin, pruritus, erythema, pale skin, sweating, oedema and flares of inflammatory skin conditions such as acne, rosacea, atopic dermatitis, pigmentation disorders and skin superinfection such as viral reactivation. Acute stresses can also induce scalp sensitivity, telogen effluvium and worsen alopecia.

[Clinical characteristics of "classical" and "non-classical" paraneoplastic neurological syndrome].

Objective: To explore the clinical features of classical and non-classical paraneoplastic neurological syndrome (PNS). Methods: From 2015 to 2020, 48 cases of definite PNS admitted to the First Affiliated Hospital of University of Science and Technology of China were retrospectively collected, and classification, clinical characteristics, onconeural antibodies and primary tumors were analyzed. The included cases were divided into classical and non-classical groups according to Graus criteria, and the differences of clinical characteristics, onconeural antibodies, combined tumors, time of diagnosis and mortality were compared between the two groups. Results: Among the 48 confirmed patients, 21 (43.8%) were positive for well-characterized onconeural antibodies. There were 28 cases (58.3%) and 20 cases (41.7%) in classic and non-classical PNS groups, respectively. No significant differences of age, sex, clinical involvement site, characteristic positive antibody type, tumor diagnosis rate and follow-up mortality were found between the two groups (all P>0.05). The time of diagnosis in the non-classical PNS group was 3.0 (2.0, 6.5) months, which was significantly longer than that in the classical PNS group 1.0(0.6, 3.0) months (P<0.05). Meanwhile, the combination rate of non-characteristic antibodies in the classical PNS group (10 cases, 35.7%) was significantly higher than that in the non-classical PNS group (1 case, 5.0%) (P=0.016). During the follow-up, 39 patients (81.3%) with tumor were confirmed, and 29 patients (60.4%) were diagnosed with PNS before the tumor was found. Conclusions: The"non-classical"PNSs are common in clinical settings. Diagnosis may be delayed due to the nonclassical symptoms of the patients. When patients have clinical symptoms related to PNS, onconeural antibodies should be detected and the relevant tumors should also be screened. Patients have positive antibodies but with no tumors should be closely followed up for more than 5 years.