Objective To explore the biomarkers and potential mechanisms of chronic restraint stress-induced myocardial injury in hyperlipidemia ApoE-/-mice.Methods The hyperlipidemia combined with the chronic stress model was established by restraining the ApoE-/-mice.Proteomics and bioinformatics techniques were used to describe the characteristic molecular changes and related regulatory mechanisms of chronic stress-induced myocardial injury in hyperlipidemia mice and to explore potential diagnostic biomarkers.Results Proteomic analysis showed that there were 43 significantly up-regulated and 58 sig-nificantly down-regulated differentially expressed proteins in hyperlipidemia combined with the restraint stress group compared with the hyperlipidemia group.Among them,GBP2,TAOK3,TFR1 and UCP1 were biomarkers with great diagnostic potential.KEGG pathway enrichment analysis indicated that fer-roptosis was a significant pathway that accelerated the myocardial injury in hyperlipidemia combined with restraint stress-induced model.The mmu_circ_0001567/miR-7a/Tfr-1 and mmu_circ_0001042/miR-7a/Tfr-1 might be important circRNA-miRNA-mRNA regulatory networks related to ferroptosis in this model.Conclusion Chronic restraint stress may aggravate myocardial injury in hyperlipidemia mice via ferrop-tosis.Four potential biomarkers are selected for myocardial injury diagnosis,providing a new direction for sudden cardiac death(SCD)caused by hyperlipidemia combined with the restraint stress.

Objective: To identify the maximum tolerated dose (MTD) of docetaxel combined with a fixed dose of cisplatin (75 mg/m 2 ) delivered as hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with ovarian cancer. Methods: In this phase I trial, a time-to-event Bayesian optimal interval design was used.Docetaxel was given at a starting dose of 60 mg/m2 and was increased in 5 mg/m2 increments until the MTD was determined or the maximum dose level of 75 mg/m2 was reached. The doselimiting toxicity (DLT) rate was set at 25%, with a total sample size of 30 patients. HIPEC was delivered immediately following debulking surgery at a target temperature of 43°C for 90 minutes. Results: From August 2022 to November 2022, 30 patients were enrolled. Among the patients who received a dose of docetaxel ≤65 mg/m2 , no DLT was reported. DLTs were observed in one patient who received 70 mg/m2 docetaxel (grade 3 anaemia) and in three patients who received 75 mg/m2 docetaxel (one case of grade 3 anaemia, one case of grade 3 hepatic impairment and one case of grade 4 thrombocytopenia). Patients treated with docetaxel 75 mg/m2 in combination with cisplatin 75 mg/m2 had an estimated DLT rate of 25%, which was the closest to the target DLT rate and was therefore chosen as the MTD. Conclusion Docetaxel, in combination with a fixed dose of cisplatin (75 mg/m2), can be used safely at intraperitoneal doses of 75 mg/m2 in ovarian cancer patients who received HIPEC (43°C, 90 minutes) following debulking surgery.

Objective: To identify the maximum tolerated dose (MTD) of docetaxel combined with a fixed dose of cisplatin (75 mg/m 2 ) delivered as hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with ovarian cancer. Methods: In this phase I trial, a time-to-event Bayesian optimal interval design was used.Docetaxel was given at a starting dose of 60 mg/m2 and was increased in 5 mg/m2 increments until the MTD was determined or the maximum dose level of 75 mg/m2 was reached. The doselimiting toxicity (DLT) rate was set at 25%, with a total sample size of 30 patients. HIPEC was delivered immediately following debulking surgery at a target temperature of 43°C for 90 minutes. Results: From August 2022 to November 2022, 30 patients were enrolled. Among the patients who received a dose of docetaxel ≤65 mg/m2 , no DLT was reported. DLTs were observed in one patient who received 70 mg/m2 docetaxel (grade 3 anaemia) and in three patients who received 75 mg/m2 docetaxel (one case of grade 3 anaemia, one case of grade 3 hepatic impairment and one case of grade 4 thrombocytopenia). Patients treated with docetaxel 75 mg/m2 in combination with cisplatin 75 mg/m2 had an estimated DLT rate of 25%, which was the closest to the target DLT rate and was therefore chosen as the MTD. Conclusion Docetaxel, in combination with a fixed dose of cisplatin (75 mg/m2), can be used safely at intraperitoneal doses of 75 mg/m2 in ovarian cancer patients who received HIPEC (43°C, 90 minutes) following debulking surgery.

Objective: To identify the maximum tolerated dose (MTD) of docetaxel combined with a fixed dose of cisplatin (75 mg/m 2 ) delivered as hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with ovarian cancer. Methods: In this phase I trial, a time-to-event Bayesian optimal interval design was used.Docetaxel was given at a starting dose of 60 mg/m2 and was increased in 5 mg/m2 increments until the MTD was determined or the maximum dose level of 75 mg/m2 was reached. The doselimiting toxicity (DLT) rate was set at 25%, with a total sample size of 30 patients. HIPEC was delivered immediately following debulking surgery at a target temperature of 43°C for 90 minutes. Results: From August 2022 to November 2022, 30 patients were enrolled. Among the patients who received a dose of docetaxel ≤65 mg/m2 , no DLT was reported. DLTs were observed in one patient who received 70 mg/m2 docetaxel (grade 3 anaemia) and in three patients who received 75 mg/m2 docetaxel (one case of grade 3 anaemia, one case of grade 3 hepatic impairment and one case of grade 4 thrombocytopenia). Patients treated with docetaxel 75 mg/m2 in combination with cisplatin 75 mg/m2 had an estimated DLT rate of 25%, which was the closest to the target DLT rate and was therefore chosen as the MTD. Conclusion Docetaxel, in combination with a fixed dose of cisplatin (75 mg/m2), can be used safely at intraperitoneal doses of 75 mg/m2 in ovarian cancer patients who received HIPEC (43°C, 90 minutes) following debulking surgery.

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

Organoids are three-dimensional structures formed by self-organizing growth of cells in vitro, which own many structures and functions similar with those of corresponding in vivo organs. Although the organoid culture technologies are rapidly developed and the original cells are abundant, the organoid cultured by current technologies are rather different with the real organs, which limits their application. The major challenges of organoid cultures are the immature tissue structure and restricted growth, both of which are caused by poor functional vasculature. Therefore, how to develop the vascularization of organoids has become an urgent problem. We presently reviewed the progresses on the original cells of organoids and the current methods to develop organoids vascularization, which provide clues to solve the above-mentioned problems.
Humans ; Organoids ; Neovascularization, Pathologic ; Technology

OBJECTIVE: To establish a new digital polymerase chain reaction (dPCR) system for the detection of BCR-ABL fusion gene in patients with chronic myeloid leukemia (CML), and explore its analytical performance and clinical applicability in the detection of BCR-ABL^p190/210/230. METHODS: A new dPCR system for detecting BCR-ABL^p190/210/230 was successfully developed, and its sensitivity difference with qPCR and improvement of drug side effects in patients with CML during drug reduction or withdrawal were compared. RESULTS: Among 176 samples, qPCR and dPCR showed high consistency in the sensitivity of detecting BCR-ABL (82.39%), and the positive rate of dPCR was about 5 times higher that of qPCR (20.45% vs 3.98%). During follow-up, blood routine (25% vs 10%), kidney/liver/stomach (25% vs 20%) and cardiac function (10% vs 0) were significantly improved after drug reduction or withdrawal in patients with initial dPCR negative compared with before drug reduction or withdrawal. CONCLUSIONS This new dPCR detection system can be applied to the detection of BCR-ABL^p190/210/230. It has better consistency and higher positive detection rate than qPCR. Drug withdrawal or dose reduction guided by dPCR has a certain effect on improving drug side effects.
Humans ; Fusion Proteins, bcr-abl/genetics* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis* ; Polymerase Chain Reaction ; Drug-Related Side Effects and Adverse Reactions ; Reverse Transcriptase Polymerase Chain Reaction

Objective:To examine the ultrasound images, clinical features, intraoperative conditions, and pathological features of ovarian clear cell carcinoma(OCCC)during perimenopause, in order to improve the early diagnosis of OCCC via ultrasound examination.Methods:A retrospective analysis of 29 patients, aged 42-72(56.8±7.4)years, who were surgically treated and pathologically diagnosed with OCCC at our hospital between 1 September 2015 and 31 December 2022, including 10 in the non-menopausal phase, 3(10.3%)in early menopausal transition, 7(24.1%)in late menopausal transition, and 19(65.5%)in the post-menopausal phase.The number of pregnancies(1.86±1.04)and the number of births(0.97±0.56)were also recorded.Results:In 29 cases, the masses contained solid components, and the ultrasound manifestations were as follows: (1)single-compartment cystic masses(solid components accounted for <50% of the total volume)were found in 11 cases, with clear borders, regular morphology, ground-glass echoes inside the cystic cavity, multiple solid protrusions inside the cystic cavity, and blood flow signals inside the solid components on color Doppler flow imaging(CDFI); (2)multi-compartment cystic masses(solid components accounted for <50% of the total volume)occurred in 8 cases, with largely clear borders, ground-glass echoes inside the cystic cavity, multiple solid protrusions inside the cavity, thick walls where the protrusions were attached, varying thickness of walls separating the cystic cavities, and blood flow signals inside the solid components, walls where there were solid attachments and thicker parts of the separating walls on CDFI; (3)there were 7 cases with predominantly solid cystic masses(the solid components accounted for >50% of the total volume), unclear borders, poor translucency, irregular morphology of the solid components, uneven internal echoes, and blood flow signals in the solid component on CDFI; (4)solid masses(the solid components accounted for >95%of the total volume)were seen in 3 cases with unclear borders, irregular morphology, uneven internal echoes, and a small number of cystic cavities(cystic portion <5%), with poor translucency in the cystic cavities and blood flow signals in the solid components on CDFI.Intraoperative exploration of ascites was performed in 17 cases, and adhesion between the mass and surrounding organs was found in 27 cases.Postoperative pathological results revealed 26 cases with high grade tumors and 3 cases with intermediate grade tumors.There were 3 cases with bilateral OCCC, 13 with left side OCCC and 13 with right side OCCC.According to the FIGO pathological staging system, 12 cases were in stage Ⅰ, 10 in stage Ⅱ, 5 in stage Ⅲ and 2 in stage Ⅳ.Comparison of different pathological stages(early stages Ⅰ and Ⅱ versus late stages Ⅲ and Ⅳ)showed statistically significant differences in the ratio of pathological stages between patients with different ultrasonographic manifestations( χ2=11.163, P<0.05), and the results of two-by-two comparisons showed that OCCC patients with ultrasonographic manifestations of solid masses(solid component accounting for >95%of the total volume)were more often in the late stage at the time of onset, while OCCC patients with a high number of cystic components within the lesions were more likely to be in the early stage at the time of onset.OCCC patients with more cystic components in the lesions tended to have an earlier onset and a better prognosis. Conclusions:When ultrasound imaging shows primarily a single chamber cystic solid mass in a patient in the perimenopausal phase with an endometriosis history, together with signs of specialized examination and pelvic adhesion during transvaginal sonography, a diagnosis of OCCC should be suspected.It is of great significance to pay attention to transvaginal sonography examination, ultrasound image features and clinical symptoms in perimenopausal women for the early diagnosis of OCCC.

OBJECTIVES: To study the early clinical efficacy of combined therapy of stage 4 neuroblastoma. METHODS: A retrospective analysis was performed on the medical data and follow-up data of 14 children with stage 4 neuroblastoma who were diagnosed in Hong Kong University-Shenzhen Hospital from January 2016 to June 2021. RESULTS: The median age of onset was 3 years and 7.5 months in these 14 children. Among these children, 9 had positive results of bone marrow biopsy, 4 had N-Myc gene amplification, 13 had an increase in neuron-specific enolase, and 7 had an increase in vanilmandelic acid in urine. Based on the results of pathological examination, differentiated type was observed in 6 children, undifferentiated type in one child, mixed type, in one child and poorly differentiated type in 6 children. Of all the children, 10 received chemotherapy with the N7 regimen (including 2 children receiving arsenic trioxide in addition) and 4 received chemotherapy with the Rapid COJEC regimen. Thirteen children underwent surgery, 14 received hematopoietic stem cell transplantation, and 10 received radiotherapy. A total of 8 children received Ch14.18/CHO immunotherapy, among whom 1 child discontinued due to anaphylactic shock during immunotherapy, and the other 7 children completed Ch14.18/CHO treatment without serious adverse events, among whom 1 child was treated with Lu177 Dotatate 3 times after recurrence and is still undergoing chemotherapy at present. The median follow-up time was 45 months for all the 14 children. Four children experienced recurrence within 2 years, and the 2-year overall survival rate was 100%; 4 children experienced recurrence within 3 years, and 7 achieved disease-free survival within 3 years. CONCLUSIONS Multidisciplinary combined therapy is recommended for children with stage 4 neuroblastoma and can help them achieve better survival and prognosis.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Child ; Child, Preschool ; Combined Modality Therapy ; Humans ; Infant ; Neuroblastoma/drug therapy* ; Positron-Emission Tomography ; Radionuclide Imaging ; Retrospective Studies ; Treatment Outcome

Inflammation is the key pathogenic feature of heart failure （HF）， and its overexpression can cause myocardial hypertrophy， apoptosis and fibrosis， aggravating the process of HF. Macrophages are important immune cells in human body with high heterogeneity， which involve in inflammation response and maintain heart homeostasis. Macrophage polarization is a dynamic process. Under the stimulation of different microenvironment， it can polarize two subsets， including classically activated M1 type and alternatively activated M2 type， which are antagonistic to each other. When macrophages polarize into the pro-inflammatory phenotype （M1）， the inflammatory response is initiated， the anti-inflammatory phenotype （M2） plays a role in inhibiting inflammation and repairing tissue. At the same time， in different stages of development of HF， M1 and M2 macrophages can be transformed into each other， which is similar to the connotation of Yin-yang restriction， balance and transformation of traditional Chinese medicine （TCM） theory. Based on this， this paper intends to clarify the relationship between M1 and M2 macrophages by Yin-yang theory， proposing that the clinical prevention and treatment of HF should pay attention to regulating micro and macro inflammatory responses， regulating macrophage polarization， and achieving the balance between anti-inflammatory and pro-inflammation， which is consistent with the balance of Yin-yang in TCM theory. It can provide a new target and direction for TCM treatment of HF.