ObjectiveThis study leverages structural data from antigen-antibody complexes of the influenza A virus neuraminidase (NA) protein to investigate the spatial recognition relationship between the antigenic epitopes and antibody paratopes. MethodsStructural data on NA protein antigen-antibody complexes were comprehensively collected from the SAbDab database, and processed to obtain the amino acid sequences and spatial distribution information on antigenic epitopes and corresponding antibody paratopes. Statistical analysis was conducted on the antibody sequences, frequency of use of genes, amino acid preferences, and the lengths of complementarity determining regions (CDR). Epitope hotspots for antibody binding were analyzed, and the spatial structural similarity of antibody paratopes was calculated and subjected to clustering, which allowed for a comprehensively exploration of the spatial recognition relationship between antigenic epitopes and antibodies. The specificity of antibodies targeting different antigenic epitope clusters was further validated through bio-layer interferometry (BLI) experiments. ResultsThe collected data revealed that the antigen-antibody complex structure data of influenza A virus NA protein in SAbDab database were mainly from H3N2, H7N9 and H1N1 subtypes. The hotspot regions of antigen epitopes were primarily located around the catalytic active site. The antibodies used for structural analysis were primarily derived from human and murine sources. Among murine antibodies, the most frequently used V-J gene combination was IGHV1-12*01/IGHJ2*01, while for human antibodies, the most common combination was IGHV1-69*01/IGHJ6*01. There were significant differences in the lengths and usage preferences of heavy chain CDR amino acids between antibodies that bind within the catalytic active site and those that bind to regions outside the catalytic active site. The results revealed that structurally similar antibodies could recognize the same epitopes, indicating a specific spatial recognition between antibody and antigen epitopes. Structural overlap in the binding regions was observed for antibodies with similar paratope structures, and the competitive binding of these antibodies to the epitope was confirmed through BLI experiments. ConclusionThe antigen epitopes of NA protein mainly ditributed around the catalytic active site and its surrounding loops. Spatial complementarity and electrostatic interactions play crucial roles in the recognition and binding of antibodies to antigenic epitopes in the catalytic region. There existed a spatial recognition relationship between antigens and antibodies that was independent of the uniqueness of antibody sequences, which means that antibodies with different sequences could potentially form similar local spatial structures and recognize the same epitopes.

Objective:To investigate the feasibility of using body surface marker localization method to determine the correct position of catheter tip (lower 1/3 of the superior vena cava or the junction of superior vena cava and right atrium) in totally implantable venous access port (TIVAP) implantation via internal jugular vein approach.Methods:The clinical data of 220 patients who underwent TIVAP implantation in Beijing Tongren Hospital, Capital Medical University from June 2019 to June 2021 were retrospectively analyzed. Among them, 168 patients used the internal jugular vein approach. According to the method implemented for determining the length of central venous catheter (CVC) during the operation, the patients were divided into two groups: 136 patients using the body surface marker localization method were defined as the study group; and the remaining 32 cases treated by the intraoperative X-ray fluoroscopic localization method were defined as the control group. The difference in the excellent or good rate of CVC tip position immediately after implantation and the time of implantation was compared between the two groups. In addition, the correlation between the length of CVC indwelling, height, age, and the distance between the catheter tip and tracheal carina was analyzed for the patients with right and left internal jugular vein catheterization. Kolmogorov-Smirnov test was used for statistical distribution of measurement data. Normal distribution of measurement data was expressed as mean ± standard deviation ( ± s), independent sample t-test was used for comparison between groups. Chi-square test was used for comparison between counting data. With TIVAP catheter indenture length as dependent variable and height as independent variable, Pearson correlation analysis was performed, the relationship equation between ideal catheter indenture length and patient height was analyzed by unitary linear regression. Results:When the CVC tip was located at the second intercostal space, the third sternocostal joint and the third intercostal space, the corresponding probability of being in the correct position was 34.8%, 83.3% and 95.0% respectively. The third sternocostal joint or the third intercostal space had a higher probability of correct CVC tip location than the second intercostal space, and the difference were statistically significant ( P<0.001). Furthermore, there was no significant difference in the possibility of the CVC tip located in the correct position between the third sternocostal joint and the third intercostal space ( P=0.149). Compared with the control group (before adjusting catheter position), the proportion of excellent or good CVC position in the study group was significantly improved (94.1% vs 46.9%), and the difference was statistically significant ( χ2=41.99, P<0.001); while the total operation time was significantly shortened [(33.04±6.69) min vs (42.50±5.54) min], and the difference was statistically significant ( P<0.05). There was a linear correlation between the length of CVC insertion and height. Indwelling catheter length via right internal jugular vein approach (cm) =0.159× height (cm)-1.284 ( r=0.597, r2=0.356, P<0.001); length of catheter indwelling through the left approach (cm) =0.097× height (cm) + 12.139 ( r=0.322, r2=0.104, P=0.020). Conclusions:The third sternocostal joint or the third intercostal space would be the corresponding correct surface landmark of the CVC tip when the body surface marker localization method was adopted during the TIVAP implantation via the internal jugular vein approach. Compared with the intraoperative X-ray fluoroscopy localization, the operation time is significantly shortened with the application of the body surface marker localization method. This technique is simple and easy to master and has high reliability in determining the length of catheter and the position of CVC tip.

Objective: To explore the surgical strategy of nipple areola complex (NAC) management in central breast cancer. Methods: A retrospective analysis was conducted on 164 cases of central breast cancer who underwent surgery treatment from December 2017 to December 2020 in the Breast Center of Beijing Tongren Hospital, Capital Medical University. Prior to the surgery, the tumor-nipple distance (TND) and the maximum diameter of the tumor were measured by magnetic resonance imaging (MRI). The presence of nipple invagination, nipple discharge, and nipple ulceration (including nipple Paget's disease) were recorded accordingly. NAC was preserved in patients with TND≥0.5 cm, no signs of NAC invasion (nipple invagination, nipple ulceration) and negative intraoperative frozen pathological margin. All patients with signs of NAC involvement, TND<0.5 cm or positive NAC basal resection margin confirmed by intraoperative frozen pathology underwent NAC removal. χ(2) test or Fisher exact test was used to analyze the influencing factors. Results: Of the 164 cases of central breast cancer, 73 cases underwent breast-conserving surgery, 43 cases underwent nipple-areola complex sparing mastectomy (NSM), 34 cases underwent total mastectomy, and the remaining 14 cases underwent skin sparing mastectomy (SSM). Among the 58 cases of NAC resection (including 34 cases of total mastectomy, 14 cases of SSM, and 10 cases of breast-conserving surgery), 25 cases were confirmed tumor involving NAC (total mastectomy in 12 cases, SSM in 9 cases, and breast-conserving surgery in 4 cases). The related factors of NAC involvement included TND (P=0.040) and nipple invagination (P=0.031). There were no correlations between tumor size (P=0.519), lymph node metastasis (P=0.847), bloody nipple discharge (P=0.742) and NAC involvement. During the follow-up period of 12 to 48 months, there was 1 case of local recurrence and 3 cases of distant metastasis. Conclusions: For central breast cancer, data suggest that patients with TND≥0.5cm, no signs of NAC invasion (nipple invagination, nipple ulceration) and negative NAC margin in intraoperative frozen pathology should be treated with NAC preservation surgery, whereas for those with TND<0.5 cm or accompanied by signs of NAC invasion, NAC should be removed. In addition, nipple reconstruction can be selected to further improve the postoperative appearance of patients with central breast cancer.
Breast Neoplasms/surgery* ; Female ; Humans ; Mammaplasty/methods* ; Mastectomy/methods* ; Nipples/surgery* ; Retrospective Studies

Objective:To explore the individualized surgical methods for elderly breast cancer patients.Methods:Elderly patients(aged≥70 years)with stage 0-Ⅲ breast cancer admitted to Beijing Tongren Hospital Affiliated to Capital Medical University from January 2013 to June 2020 were retrospectively analyzed.They were divided into three groups based on surgical methods: breast-conserving surgery, nipple-areola complex-sparing mastectomy and traditional mastectomy.Age, tumor size, lymph node involvement, hormone receptor status, anesthesia mode, surgical operation mode and patient prognosis were retrospectively analyzed.Results:A total of 144 patients(147 cases)were followed up for 8-96(36.5±10.7)months, with a median of 27 months.The overall survival rate was 88.9%, with breast cancer-related deaths at 6.3%, non-breast cancer-related deaths at 4.9%, local recurrence at 3.5%, and systemic metastasis at 5.6%.Among the three groups, 38.5%, 82.0% and 73.3%, respectively, received general anesthesia.Breast-conserving surgery showed the shortest operation time[(71.7±31.6)min vs.(84.8±24.8)min vs.(100.0±34.4)min, F=7.264, P=0.001], the lowest postoperative drainage volume[(39.5±75.4)ml vs.(154.92±135.6)ml vs.(334.1±287.2)ml, F=31.481, P<0.001]and the shortest drainage duration[(2.8±3.3)d vs.(6.3±2.8)d vs.(8.5±3.7)d, F=38.101, P<0.001]. Conclusions:The surgical treatment of elderly patients with breast cancer should be based on comprehensive evaluation and accurate molecular typing.Breast-conserving surgery is the preferred surgical method for elderly patients with hormone receptor-positive and cN0 breast cancer.Mastectomy with skin and nipple areola preservation where appropriate can improve the therapeutic effect and quality of life for elderly breast cancer patients.

Breast-contour preservation(BCP)encompasses all strategies to preserve the contour of the breast following breast-conserving surgery (BCS) and immediate postmastectomy breast reconstruction (IBR). With the continuous advancement of breast surgery, postoperative outcomes and quality of life of breast cancer patients have been significantly improved. Previous studies reported on BCP as a new comprehensive parameter for evaluating outcomes of breast cancer treatment. Based on preoperative comprehensive evaluation of patients′ general condition, characteristic of breast tumor, and breast morphology, individualized surgical strategy is formulated to improve BCP for early-stage breast cancer and improve postoperative outcomes of patients. Combined with the morphological characteristics of Chinese women′s breasts, breast contour can be preserved not only by BCS and IBR, but also by nipple-areola complex-sparing mastectomy in some breast cancer patients, thereby reducing psychosomatic impact as a result of losing breast mound.

Objective:To investigate the efficacy and clinical value of two-stage implant-based breast reconstruction after total mastectomy for breast cancer patients.Methods:Thirty-two patients with breast cancer, who underwent nipple-sparing mastectomy or skin-sparing mastectomy, primary skin expander implantation, and permanent implant replacement after radiotherapy from January 2018 to December 2020 in the Breast Center, Beijing Tongren Hospital, Capital Medical University were analyzed retrospectively. Record the operation time of the patient, the interval between replacement surgery and radiotherapy, prosthesis volume, the difference between the volume of 0.9% sodium chloride solution in the dilator and the volume of the prosthesis, the retention time of the postoperative drainage tube, the satisfaction of the breast shape and the complications after the replacement.Results:The average operation time was (67.81±19.71) min; the average time interval between replacement surgery and radiotherapy was (9.88±2.00) months; the average volume of 0.9% sodium chloride solution in the dilator was (225.47±56.83) mL, and the average prosthesis volume was (259.06±70.88) mL, the average difference between the volume of the prosthesis and the volume of 0.9% sodium chloride solution in the dilator was (33.59±14.88) mL; the volume of the prosthesis is increased by an average of (13.65±5.19)% compared with the dilator; the average time of drainage tube retained after the operation was (9.03±1.40) d; satisfaction with breast shape after replacement: excellent in 23 cases (71.9%), general in 8 cases (25.0%), poor in 1 case (3.1%); postoperative complications: incision fat liquefaction 1 case of dehiscence (3.1%), 2 cases of seroma (6.3%), no serious complications such as external exposure and removal of the prosthesis.Conclusions:For patients with breast cancer, who need breast reconstruction after mastectomy, the two-stage implant-based breast reconstruction in which the replacement operation will be carried out more than 6 months after radiotherapy is safe. Moreover, achieve better symmetry and aesthetic effect by releasing the capsule, reconstructing the inframammary fold, and necessary plastic surgery of the contralateral breast.

Objective: This study investigated the characteristics of progestin-insensitive endometrioid endometrial cancer (EEC) and atypical endometrial hyperplasia (AEH) patients receiving fertility-sparing treatments and assessed the therapeutic effects of second-line fertility-preserving treatments. Methods: Three hundred and thirty-eight patients with EEC (n=75) or AEH (n=263) receiving fertility-preserving treatment were retrospectively analyzed. ‘Progestin-insensitive’ was defined as meeting one of the following criteria: 1) presented with progressed disease at any time during conservative treatment, 2) remained with stable disease after 7 months of treatment, and/or 3) did not achieve complete response (CR) after 10 months of treatment. Clinical characteristics and treatment results of progestin-insensitive patients receiving second-line treatment and those of progestin-sensitive patients were compared. Results: Eight-two patients (59 AEH and 23 EEC) were defined as progestin-insensitive and 256 as progestin-sensitive. In multivariate analysis, body mass index ≥28.0 kg/m2 (odds ratio [OR]=1.898) and lesion size >2 cm (OR=2.077) were independent predictors of progestin-insensitive status. Compared to AEH patients, progestin-insensitive EEC patients had poorer second-line treatment responses (28-week cumulative CR rate after changing second-line treatment, 56.3% vs. 85.4%, p=0.011). No statistical difference was found in CR rate among different second-line treatments. Conclusion Obesity and larger lesion size were independent risk factors associated with progestin-insensitive status. In progestin-insensitive patients receiving second-line treatment, EEC patients had lower CR rate comparing with AEH patients. Further study with larger sample size is needed to evaluate efficacy of different second-line treatments for progestin insensitive patients.

The experiment is designed to explore pathological festures and material basis of pseadoanaphylactoid reaction induced by notoginseng total saponin preparation. Mouse pseadoanaphylactoid reaction was used, 50 ICR mice were randomly assigned to control group, positive medicine group, notoginseng total saponin preparation low-dose group, notoginseng total saponin preparation middle-dose group, notoginseng total saponin preparation high-dose group on average. They are treated by intravenous injection of test substance solutions containing 0.4% Evans blue (EB). 30 min later, scores of ear blue staining and quantitation of ear EB exudation were recorded. Another two experiment were repeated in the same way excluding EB, just to. detect the related cytokines in serum using ELISA. We found that the scores of pseudoanaphylactoid reaction in notoginseng total saponin preparation injection middle-dose group and high-dose group was evidently higher than that in control group, suggesting that notoginseng total saponin preparation injection may be can lead to pseadoanaphylactoid reaction. HE staining showed that pseadoanaphylactoid reaction induced by notoginseng total saponin preparation injection is related to inflammation. Histamine, VEGF and TNF-α levels in notoginseng total saponin preparation middle-dose group and high-dose group significantly increased (P < 0.05, P < 0.01) than control group and showed a dose-dependent manner as well as consistent with the degree of ear blue dye. While IL-6 and IL-10 content did not increase significantly in notoginseng total saponin preparation low-dose group and middle-dose group, but they significantly higher than control group (P < 0.05, P < 0.01) when it increased to quadrupe clinical concentrations, eight times of the clinical dose. So pseadoanaphylactoid reaction caused by notoginseng total saponin preparation may be related to histamine, VEGF, TNF-α, and it is possible that IL-6 and IL-10 can play a role when pseadoanaphylactoid reaction achieve a certain high degree.
Anaphylaxis ; chemically induced ; Animals ; Capillary Permeability ; drug effects ; Cytokines ; blood ; Dose-Response Relationship, Drug ; Drug Hypersensitivity ; etiology ; Mice ; Mice, Inbred ICR ; Panax notoginseng ; adverse effects ; chemistry ; Saponins ; adverse effects

Objective To observe the acute toxicity and long -term toxicity induced by Chuanping dropping pills in beagle dogs.Methods Acute toxicity test:it was used by the approximate lethal dose on Beagle dogs.Observational index included general clinical observation, weight, ingestion capacity, blood pressure, electrocardiogram, urinalysis, blood test, blood biochemical examination and pathological examination.Long-term toxicity test:Chuanping dropping pills with 0.13, 0.40, 1.19 g · kg-1 · d-1 and the hollow capsules control group in Beagle dogs were lavaged.Observational index included general physiological indices, blood test,blood biochemical examination, urinalysis, electrocardiogram, blood pressure, eye test and pathological examination.Results The approxi-mate lethal dose in beagle dogs lavaged by Chuanping dropping pills was more than 54.79 g · kg-1.Relativel safe dose in Beagle dogs lavaged by Chuanping dropping pills after 90 days was below 0.40 g · kg-1 · d-1.Conclusion Clinical dose of Chuanping dropping pills was safe and reliable.

OBJECTIVETo study the effects of carbamazepine on serum metabolic profiles in rats using nuclear magnetic resonance (NMR) spectroscopy.

METHODSTwenty-four healthy male Wistar rats were randomized into 4 groups (n=6) for daily intragastric administration of high-, medium- or low-dose carbamazepine or distilled water (control) for 7 days. Blood samples were collected from the abdominal aortic under anesthesia after the treatment to determine serum carbamazepine concentration using high-performance liquid chromatography. ¹H nuclear magnetic resonance (¹H NMR) spectra were acquired for pattern recognition analysis. Histopathological changes of the renal and liver tissues of the rats were also examined.

RESULTSSteady-state blood concentration of carbamazepine in high-, medium- and low-dose groups were 14.64 ± 1.41, 8.54 ± 1.19, and 4.56 ± 0.64 µg/ml, respectively. Slight liver swelling was found in high-dose group, but none of the groups showed renal pathologies. Compared with the control group, the high-dose carbamazepine group showed lowered serum concentrations of 1,3-diaminopropane, deoxycorticosterone, 7-dehydrocholesterol, betaine, beta-alanine, L-cystathionine, 4-methyl-2-oxovaleric acid, and creatine with increased levels of saccharides, lactate, succinic acid, acetyl phosphate, and adipic acid. Principal component analysis revealed significant differences of the metabolites between carbamazepine-treated groups and the control group. The metabolic profiles showed no differences in the kinds of metabolites although the concentrations of the metabolites varied between the carbamazepine groups.

CONCLUSIONSCarbamazepine significantly affects metabolism in normal rats. This finding provides evidence for clinical drug monitoring and drug safety of carbamazepine. NMR technique has important values for pharmacodynamic and toxicological evaluation of drugs.

Animals ; Carbamazepine ; blood ; Kidney ; pathology ; Liver ; pathology ; Magnetic Resonance Spectroscopy ; Male ; Metabolomics ; Principal Component Analysis ; Rats ; Rats, Wistar