Objective: To evaluate the incidence, treatment, and survival outcomes of Swyer syndrome with gonadal non-dysgerminoma malignant germ cell tumor (MGCT-NDG). Methods: A retrospective study was performed on Swyer syndrome patients with MGCT-NDG between January 2011 and December 2022 in Peking Union Medical College Hospital to investigate their characteristics and outcomes. Results: A total of 15 patients (4.9%, 15/307) with Swyer syndrome were identified in 307 MGCT-NDG patients. The average age at diagnosis of MGCT-NDG and Swyer syndrome were (16.8±6.7) and (16.7±6.6) years, respectively. Six cases were preoperatively diagnosed as Swyer syndrome, of which 4 cases received bilateral gonadectomy with or without hysterectomy, while the other 2 cases underwent removal of gonadal tumor and unilateral gonadectomy with hysterectomy, respectively. Of the 9 patients postoperatively diagnosed as Swyer syndrome, unilateral gonadectomy, removal of gonadal tumor, and unilateral gonadectomy with hysterectomy were performed in 6 patients, 2 patients, and 1 patient, respectively. Mixed malignant germ cell tumor (MGCT;10 cases), yolk sac tumor (4 cases), and immature teratoma (1 case) were the pathological subtypes, in the descending order. There were International Federation of Gynecology and Obstetrics (FIGO) stage Ⅰ in 6 cases, stage Ⅱ in 3 cases, stage Ⅲ in 5 cases, and stage Ⅳ in 1 case, respectively. Eleven patients received reoperation for residual gonadectomy after a average delay of (7.9±6.2) months, including 8 MGCT-NDG patients and 1 gonadoblastoma patient, no tumor involved was seen in the remaining gonads in the other 2 cases. Ten patients experienced at least one recurrence, with a median event free survival of 9 months (5, 30 months), of which 2 patients received surgery only at the time of initial treatment. All patients with recurrence received surgery and combined with postoperative chemotherapy. After a median follow-up of 25 months (15, 42 months), 10 patients were disease-free, 3 patients died of the tumor, 1 died of side effects of leukemia chemotherapy, and 1 survived with disease. Conclusion: The incidence rate of Swyer syndrome in patients with MGCT-NDG is about 4.9%; timely diagnosis and bilateral gonadectomy should be emphasized to reduce the risk of reoperation and second carcinogenesis in this population.
Female ; Humans ; Retrospective Studies ; Gonadal Dysgenesis, 46,XY/surgery* ; Gonadoblastoma/surgery* ; Neoplasms, Germ Cell and Embryonal/surgery* ; Ovarian Neoplasms/pathology*

Objective To make an epidemiological investigation on traditional Chinese medicine(TCM)dampness syndrome manifestations in the population at risk of cerebrovascular diseases in Guangdong area.Methods A cross-sectional study was conducted to analyze the clinical data related to the risk of cerebrovascular diseases in 330 Guangdong permanent residents.The diagnosis of dampness syndrome,quantitative scoring of dampness syndrome and rating of the risk of stroke were performed for the investigation of the distribution pattern of dampness syndrome and its influencing factors.Results(1)A total of 306(92.73%)study subjects were diagnosed as dampness syndrome.The percentage of dampness syndrome in the risk group was 93.82%(258/275),which was slightly higher than that of the healthy group(48/55,87.27%),but the difference was not statistically significant(χ2 = 2.91,P = 0.112).The quantitative score of dampness syndrome in the risk group was higher than that of the healthy group,and the difference was statistically significance(Z =-2.24,P = 0.025).(2)Among the study subjects at risk of cerebrovascular disease,evaluation time(χ2 = 26.11,P = 0.001),stroke risk grading(χ2= 8.85,P = 0.031),and history of stroke or transient ischemic attack(TIA)(χ2 = 9.28,P = 0.015)were the factors influencing the grading of dampness syndrome in the population at risk of cerebrovascular disease.Conclusion Dampness syndrome is the common TCM syndrome in the population of Guangdong area.The manifestations of dampness syndrome are more obvious in the population with risk factors of cerebrovascular disease,especially in the population at high risk of stroke,and in the population with a history of stroke or TIA.The assessment and intervention of dampness syndrome should be taken into account for future project of stroke prevention in Guangdong.

Objective:To investigate the accuracy and feasibility of applying rapid immunohistochemistry(IHC) with CK5/6 antibodies in prostate biopsy tissues to assist frozen pathology diagnosis.Methods:The data of 41 patients who underwent prostate puncture and frozen tissue rapid IHC with CK5/6 antibody in Beijing Hospital from October 2022 to April 2023 were retrospectively analyzed. The median age of the patients was 76 (69, 79) years old, and the median PSA value was 12.37 (7.07, 26.17) ng/ml.The Prostate Imaging Reporting and Data System (PI-RADS) scores of the target lesions were all ≥3. The PI-RADS score of 9 patients(21.95%) was 3, 15 (36.59%) was 4, and 17(41.46%) was 5. The median diameter of the lesions in the MRI examination was 1.40 (1.09, 2.20) cm.Fourteen lesions (34.14%) were located in the migratory zone, 23 (56.10%) were located in the peripheral zone, and 4 (9.76%) involved both peripheral and migratory zone lesions. Transperineal cognitive fusion targeted combined systematic biopsy was used, and intraoperatively, 1 additional needle was taken from each of the target and non-target areas for frozen pathology section, and hematoxylin eosin(HE) staining and rapid IHC staining with CK5/6 antibody was performed, then the frozen remaining tissue was HE staining and CK5/6 IHC staining. Data such as HE and rapid IHC results of frozen pathology sections and HE and IHC results of routine sections of the frozen remaining tissues, International Society of Urological Pathology (ISUP) grading groupings(GG), and actual diagnostic results of targeted combined systematic puncture were recorded. Using the routine IHC results of the same needle tissue as the gold standard, the sensitivity and positive predictive value of applying rapid IHC frozen pathology to diagnose prostate cancer and the accuracy of its pathological GG were analyzed.Results:Among the 41 patients, a total of 35 cases were diagnosed with prostate cancer(PCa) by HE staining in frozen section of target tissue, with a positivity rate of 85.37%(35/41). Among these, there were 17 cases (48.57%) in ISUP GG 1, 8 cases (22.86%) in GG 2, 4 cases (11.43%) in GG 3, and 6 cases (17.14%) in GG 4 to 5. In addition, a total of 35 cases were diagnosed with PCa by HE staining in frozen remaining section of target tissue, with a positivity rate of 85.37%(35/41). Among these, there were 17 cases (48.57%) in ISUP GG 1, 8 cases (22.86%) in GG 2, 4 cases (11.43%) in GG 3, and 6 cases (17.14%) in GG 4 to 5. The results of rapid IHC of target tissue: 35 cases were negative for CK5/6 expression and 6 cases were positive. The results of routine IHC of target tissue: 35 cases were negative for CK5/6 expression and 6 cases were positive. The results of rapid IHC of non-target tissue: 12 cases were negative for CK5/6 expression and 29 cases were positive. The results of routine IHC of non-target tissue: 12 cases were negative for CK5/6 expression and 29 cases were positive. Thirty-five cases of target tissue rapid IHC diagnosis of PCa were in complete agreement with routine IHC diagnosis, with a false-positive rate of 0, a sensitivity of 100.00% (35/35) and a positive predictive value of 100.00% (35/35). Twelve cases of non-target tissue rapid IHC diagnosis of PCa were in complete agreement with routine IHC diagnosis, with a false-positive rate of 0, a sensitivity of 100.00% (35/35), and a positive predictive value of 100.00% (12/12).Conclusions:The preliminarily study results confirmed that the application of rapid IHC with CK5/6 antibodies in prostate biopsy tissues assisted frozen pathology diagnosis with high accuracy, but the reliability of rapid IHC technology in assisting frozen pathological diagnosis during puncture surgery still needs further validation through large sample size prospective studies.

italic>Artemisia argyi is a traditional Chinese medicine in China, which is used as medicine with its leaves. The leaves of A. argyi mainly contain flavonoids, phenolic acids, volatile oils and other compounds, and have a variety of pharmacological activities. AP2/ERF transcription factors are abundant in plants and are mainly involved in plant growth and development, abiotic stress response and secondary metabolite biosynthesis regulation. However, there are few reports on the AP2/ERF gene family and its functions in A. argyi. In this study, we systematically identified the AP2/ERF gene family in A. argyi genome, and analyzed its phylogenetic tree, protein physicochemical properties, subcellular localization, conserved motifs, promoter elements, and expression patterns. The results showed that a total of 204 AP2/ERF transcription factors were identified in A. argyi genome, encoding proteins consisting of 88-483 amino acids with a relative molecular mass of 10-52.94 kDa and a theoretical isoelectric point of 4.62-9.88. Subcellular prediction showed that the majority of AP2/ERFs were located in the nucleus, cytoplasm, and the minority of them is located in the membrane and chloroplasts. According to the Arabidopsis AP2/ERF family classification, A. argyi AP2/ERF proteins were divided into four subfamilies: Soloist, AP2, ERF (B3, B4, B5, B6), and DREB (A1, A2, A4, A5, A6), among which DREB family accounted for the largest proportion, and the same subfamily had similar conserved motifs. cis-Acting element analysis showed that AP2/ERF promoters have a large number of elements responding to light and abiotic stress. Expression pattern analysis showed that most of the genes of the AP2/ERF family were dominantly expressed mainly in roots and stems, of which 19 were dominantly expressed in leaves, 77 would be induced to be expressed by methyl jasmonate, of which 16 genes were both dominantly expressed in leaves and induced to be expressed by methyl jasmonate, and these AP2/ERF genes may be the key regulatory genes for the synthesis of active ingredients in A. argyi leaves.This study lays the foundation for the functional study of AP2/ERF family genes and their regulating roles in the active components biosynthesis in A. argyi leaves.

Objective:To investigate the clinical efficacy and safety of ixazomib-containing regimens in the treatment of patients with multiple myeloma(MM).Methods:A retrospective analysis was performed on the clinical efficacy and adverse reactions of 32 MM patients treated with a combined regimen containing ixazomib in the Hematology Department of the First People's Hospital of Lianyungang from January 2020 to February 2022.Among the 32 patients,15 patients were relapsed and refractory multiple myeloma(R/RMM)(R/RMM group),17 patients who responded to bortezomib induction therapy but converted to ixazomib-containing regimen due to adverse events(AE)or other reasons(conversion treatment group).The treatment included IPD regimen(ixazomib+pomalidomide+dexamethasone),IRD regimen(ixazomib+lenalidomide+dexamethasone),ICD regimen(ixazomib+cyclophosphamide+dexamethasone),ID regimen(ixazomib+dexamethasone).Results:Of 15 R/RMM patients,overall response rate(ORR)was 53.3％(8/15),among them,1 achieved complete response(CR),2 achieved very good partial response(VGPR)and 5 achieved partial response(PR).The ORR of the IPD,IRD,ICD and ID regimen group were 100％(3/3),42.9％(3/7),33.3％(1/3),50％(1/2),respectively,there was no statistically significant difference in ORR between four groups(x2=3.375,P=0.452).The ORR of patients was 50％after first-line therapy,42.9％after second line therapy,60％after third line therapy or more,with no statistically significant difference among them(x2=2.164,P=0.730).In conversion treatment group,ORR was 88.2％(15/17),among them,6 patients achieved CR,5 patients achieved VGPR and 4 patients achieved PR.There was no statistically significant difference in ORR between the IPD(100％,3/3),IRD(100％,6/6),ICD(100％,3/3)and ID(60％,3/5)regimen groups(x2=3.737,P=0.184).The median progression-free survival(PFS)time of R/RMM patients was 9 months(95％CI:6.6-11.4 months),the median overall survival(OS)time was 18 months(95％CI:11.8-24.4 months).The median PFS time of conversion treatment group was 15 months(95％CI:7.3-22.7 months),the median OS time not reached.A total of 10 patients suffered grade 3-4 adverse event(AE).The common hematological toxicities were leukocytopenia,anemia,thrombocytopenia.The common non-hematological toxicities were gastrointestinal symptoms(diarrhea,nausea and vomit),peripheral neuropathy,fatigue and infections.Grade 1-2 peripheral neurotoxicity occurred in 7 patients.Conclusion:The ixazomib-based chemotherapy regimens are safe and effective in R/RMM therapy,particularly for conversion patients who are effective for bortezomib therapy.The AE was manageable and safe.

Objective:To investigate the independent influencing factors of body mass index (BMI) growth risk during breast cancer treatment and establish a predictive model, and validate its predictive efficacy.Methods:A retrospective cohort study was conducted by a convenience sampling method. 306 eligible breast cancer patients underwent follow-up at the Tianjin Medical University Cancer Hospital between January and May 2023 were selected as the modeling group. The BMI changes of the modeling group patients were monitored during the study period. Patients with BMI changed < ± 0.5 kg/m 2 were classified as the stable group, while those with BMI changed ≥ 0.5 kg/m 2 were classified as the growth group. Factor analysis was conducted, and a predictive model was established. The fitting effect was verified by the Hosmer-Lemeshow test, and the receiver operating characteristic (ROC) curve was drawn to verify the model′s predictive ability. 110 eligible breast cancer patients underwent follow-up at the Tianjin Medical University Cancer Hospital between June and August 2023 were selected as the validation group to verify the predictive effect of the model. Results:The age of the modeling group patients was (48.89 ± 7.78) years, BMI was (25.53 ± 1.39) kg/m 2 and the age of the validation group patients was (50.18 ± 7.70) years, BMI was(24.31 ± 0.86) kg/m 2, both groups were female, there were no significant differences between the two groups (all P>0.05). Axillary lymph node dissection ( OR=4.196, 95% CI 3.512-9.158), chemotherapy duration ( OR=2.002, 95% CI 1.001-3.003), premenopausal status ( OR=3.257, 95% CI 1.244-3.733), low health behavior capacity ( OR=5.977, 95% CI 2.878-7.893), and low physical activity ( OR=3.755, 95% CI 1.244-11.733) were identified as independent influencing factors of BMI change during breast cancer treatment (all P<0.05). The predictive model was P=0.915, with the ROC curve area of 0.950, a J-index of 0.785, a sensitivity of 0.971, and a specificity of 0.814. Internal and external validation of the model in the validation group revealed a sensitivity of 0.858, a specificity of 0.887, and an accuracy of 97.3%. Conclusion:The predictive model exhibited excellent performance and can serve as a valuable tool for formulating nursing intervention strategies to maintain the BMI stability of breast cancer patients during treatment.

UPLC-Q-Exactive-MS/MS and network pharmacology were employed to preliminarily study the active components and mechanism of Jinwugutong Capsules in the treatment of osteoporosis. Firstly, UPLC-Q-Exactive-MS/MS was employed to characterize the chemical components of Jinwugutong Capsules, and network pharmacology was employed to establish the "drug-component-target-pathway-disease" network. The key targets and main active components were thus obtained. Secondly, AutoDock was used for the molecular docking between the main active components and key targets. Finally, the animal model of osteoporosis was established, and the effect of Jinwugutong Capsules on the expression of key targets including RAC-alpha serine/threonine-protein kinase(AKT1), albumin(ALB), and tumor necrosis factor-alpha(TNF-α) was determined by enzyme-linked immunosorbent assay(ELISA). A total of 59 chemical components were identified from Jinwugutong Capsules, among which coryfolin, 8-prenylnaringenin, demethoxycurcumin, isobavachin, and genistein may be the main active components of Jinwugutong Capsules in treating osteoporosis. The topological analysis of the protein-protein interaction(PPI) network revealed 10 core targets such as AKT1, ALB, catenin beta 1(CTNNB1), TNF, and epidermal growth factor receptor(EGFR). The Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment showed that Jinwugutong Capsules mainly exerted the therapeutic effect by regulating the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT) signaling pathway, neuroactive ligand-receptor interaction, mitogen-activated protein kinase(MAPK) signaling pathway, Rap1 signaling pathway and so on. Molecular docking showed that the main active components of Jinwugutong Capsules well bound to the key targets. ELISA results showed that Jinwugutong Capsules down-regulated the protein levels of AKT1 and TNF-α and up-regulated the protein level of ALB, which preliminarily verified the reliability of network pharmacology. This study indicates that Jinwugutong Capsules may play a role in the treatment of osteoporosis through multiple components, targets, and pathways, which can provide reference for the further research.
Animals ; Tumor Necrosis Factor-alpha/genetics* ; Network Pharmacology ; Capsules ; Molecular Docking Simulation ; Phosphatidylinositol 3-Kinases ; Reproducibility of Results ; Tandem Mass Spectrometry

Objective:To investigate the independent influencing factors of wound drainage tube time delay in patients with breast cancer and establish a predictive model.Methods:Patients admitted to Tianjin Medical University Cancer Hospital from January to November 2021 were selected as the research objects. They were divided into sword modeling group (156 cases) and verification group (86 cases) according to the admission time. Delayed time to postoperative wound drainage and extubation in breast cancer patients was the end point, 95 cases of 156 patients in the modeling group whose extubation time was less than or equal to 7 days were set as the normal group, 61 cases whose extubation time were more than 7 days were set as delayed group, and the influencing factors of the two groups were compared to establish the prediction model, Hosmer-Lemeshow test was conduct to verify the fitting effect, used the ROC curve to verify the prediction model performance.Results:Univariate and multivariate Cox proportional hazards regression analysis showed that patients' high BMI, related basic disease history, operation mode, axillary lymph node dissection, breast tumor size (T3, T4) and drainage fluid volume 48 hours (≥50 ml) after operation were independent influencing factors for wound drainage tube time delay ( P<0.05). The prediction model was P=0.822, and the area under the ROC curve was 0.877, and the Youden index was 0.605, the sensitivity was 0.736, and the specificity was 0.869. The research data of 86 cases in the validation group were used as the test set for internal and external validation of the model, and the model verification was 96.51%. Conclusion:This prediction model has a good effect, providing a reference basis for clinical medical workers.

Animals ; Rats ; Explosions ; Proteomics ; Autophagy

The present study was aimed to investigate the role and mechanism of glutaminolysis of cardiac fibroblasts (CFs) in hypertension-induced myocardial fibrosis. C57BL/6J mice were administered with a chronic infusion of angiotensin II (Ang II, 1.6 mg/kg per d) with a micro-osmotic pump to induce myocardial fibrosis. Masson staining was used to evaluate myocardial fibrosis. The mice were intraperitoneally injected with BPTES (12.5 mg/kg), a glutaminase 1 (GLS1)-specific inhibitor, to inhibit glutaminolysis simultaneously. Immunohistochemistry and Western blot were used to detect protein expression levels of GLS1, Collagen I and Collagen III in cardiac tissue. Neonatal Sprague-Dawley (SD) rat CFs were treated with 4 mmol/L glutamine (Gln) or BPTES (5 μmol/L) with or without Ang II (0.4 μmol/L) stimulation. The CFs were also treated with 2 mmol/L α-ketoglutarate (α-KG) under the stimulation of Ang II and BPTES. Wound healing test and CCK-8 were used to detect CFs migration and proliferation respectively. RT-qPCR and Western blot were used to detect mRNA and protein expression levels of GLS1, Collagen I and Collagen III. The results showed that blood pressure, heart weight and myocardial fibrosis were increased in Ang II-treated mice, and GLS1 expression in cardiac tissue was also significantly up-regulated. Gln significantly promoted the proliferation, migration, mRNA and protein expression of GLS1, Collagen I and Collagen III in the CFs with or without Ang II stimulation, whereas BPTES significantly decreased the above indices in the CFs. α-KG supplementation reversed the inhibitory effect of BPTES on the CFs under Ang II stimulation. Furthermore, in vivo intraperitoneal injection of BPTES alleviated cardiac fibrosis of Ang II-treated mice. In conclusion, glutaminolysis plays an important role in the process of cardiac fibrosis induced by Ang II. Targeted inhibition of glutaminolysis may be a new strategy for the treatment of myocardial fibrosis.
Rats ; Mice ; Animals ; Rats, Sprague-Dawley ; Angiotensin II/pharmacology* ; Fibroblasts ; Mice, Inbred C57BL ; Fibrosis ; Collagen/pharmacology* ; Collagen Type I/metabolism* ; RNA, Messenger/metabolism* ; Myocardium/pathology*