This article reports a case of primary Müllerian adenosarcoma(MA)of the ovary admitted to the Obstetrics and Gynecology Hospital,Fudan University in 2022,reviews the literature on this rare disease,and shares the experience of its diagnosis and treatment.The patient was a 29-year-old unmarried woman who underwent laparoscopic resection of an ovarian lesion in another hospital.Intraoperatively,it was observed that"the right ovary was enlarged with a cauliflower-shaped mass at the lower pole,measuring about 11 cm×8 cm,unencapsulated,with a fish-like texture,which was completely excised and sent for examination."Postoperative consultation with a(tertiary)hospital in Beijing and our pathology department suggested the diagnosis of ovarian adenosarcoma.Therefore,we performed a comprehensive staged surgery for the patient,i.e.,laparoscopic right salpingo-oophorectomy,cystectomy of the left ovary,omentectomy,multiple peritoneal biopsies,and hysteroscopic resection of cervical canal lesions.The patient received four cycles of postoperative chemotherapy with paclitaxel and ifosfamide.After chemotherapy,the patient has been regular followed up and showed no signs of recurrence during the almost 2-year postoperative follow-up period.

Child ; Humans ; Adenoids/surgery* ; Hypertrophy/surgery*

Objective: To explore the efficacy and safety of Venetoclax combined with multidrug chemotherapy in patients with relapsed or refractory early T-cell precursor acute lymphoblastic leukemia (R/R ETP-ALL) . Methods: This study retrospectively analyzed 15 patients with R/R ETP-ALL who received Venetoclax combined with multidrug chemotherapy from December 2018 to February 2022. Among them, eight cases were combined with demethylated drugs, four cases were combined with demethylated drugs and HAAG chemotherapy regimen, two cases were combined with demethylated drugs and CAG regimen, and one case was combined with Cladribine. Specific usage and dosage of Venetoclax: 100 mg on day 1, 200 mg on day 2, 400 mg on day 3-28, orally; when combined with azole antifungal drugs, dosage was reduced to 100 mg/d. Results: Fifteen patients (10 males and 5 females) with R/R ETP-ALL were treated with Venetoclax and multidrug chemotherapy with a median age of 35 (12-42) years old. Of 4 refractory and 11 relapsed patients, the efficacy was evaluated on the 21th day following combined chemotherapy: the overall response rate, the complete response (CR) rate, and the CR with incomplete hematological recovery (CRi) rate were 67.7% (10/15), 60.0% (9/15), and 6.7% (1/15), respectively. For the overall study population, the 12-month overall survival (OS) rate was 60.0%, and the median OS was 17.7 months. The disease-free survival (DFS) rate of all CR patients at 12 months was 60.0%, and the median DFS did not reach. About 14 patients had Ⅲ-Ⅳ hematological toxicity, but these adverse reactions were all controllable. No adverse reaction in the nervous system and tumor lysis syndrome occurred in this study, and no adverse reaction of organs above grade Ⅲ occurred. Conclusion: Venetoclax combined with multidrug chemotherapy may be a safe and promising treatment option for patients with R/R ETP-ALL.
Male ; Female ; Humans ; Adult ; Retrospective Studies ; Treatment Outcome ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Precursor Cells, T-Lymphoid ; Leukemia, Myeloid, Acute/drug therapy*

Objective: To investigate the clinicopathological, immunohistochemical and molecular genetic characteristics of gastric carcinoma with NTRK-rearrangement/amplification. Methods: The clinicopathological data of gastric carcinoma cases with NTRK-rearrangement/amplification diagnosed from January 2011 to September 2020 at the Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, China, were collected. The clinicopathological, immunophenotypic and molecular pathological features were analyzed. The relevant literature was reviewed. Results: There were 4 cases of gastric carcinoma with NTRK-rearrangement/amplification. All 4 patients were male, aged 57-67 years (average, 63 years). Tumor sizes ranged from 3.5 to 5.2 cm (average, 4.8 cm). All tumors were in the antrum. All 4 patients underwent radical gastrectomy and were followed up after the surgery. Morphologically, all tumors showed histological features with enteroblastic-differentiated gastric carcinoma. Tumor cells showed predominantly tubular/papillary architecture, with conspicuous vesicular nuclei and pale staining or transparent cytoplasm. Immunohistochemistry showed pan-TRK expression in all cases, with various degrees of positivity in the cytoplasm. All cases were subject to NTRK1/2/3 detection using fluorescence in situ hybridization. There were NTRK translocations in 2 cases and NTRK amplifications in 2 cases. These cases were further verified by RNAseq next generation sequencing which confirmed that NTRK1 gene translocation (TPM3-NTRK1) and NTRK2 gene translocation (NTRK2-SMCHD1) occurred in two cases, respectively. Conclusions: NTRK mutation occurs less frequently in gastric cancer. In this study, the cases mainly occur in the antrum. The morphology has the characteristics of enteroblastic differentiation. The tumors have unique histological, immunophenotypic and molecular characteristics, which require much attention from pathologists to effectively guide clinicians to choose the best treatment.
Humans ; Male ; Female ; Receptor, trkA/genetics* ; Stomach Neoplasms/surgery* ; In Situ Hybridization, Fluorescence ; Biomarkers, Tumor/genetics* ; Translocation, Genetic ; Carcinoma ; Oncogene Proteins, Fusion/genetics* ; Chromosomal Proteins, Non-Histone/genetics*

BACKGROUND: Currently, more and more infertility couples are opting for combined acupuncture to improve success rate of in vitro fertilization (IVF). However, evidence from acupuncture for improving IVF pregnancy outcomes remains a matter of debate. OBJECTIVE: To quantitatively summarized the evidence of the efficacy of acupuncture among women undergoing IVF by means of systematic review and meta-analysis. METHODS: Four English (PubMed, Web of Science, EMBASE, and Cochrane Register of Controlled Clinical Trials) and Four Chinese databases (Wanfang Databases, Chinese National Knowledge Infrastructure, Chinese Science and Technology Periodical Database, and SinoMed) were searched from database inception until July 2, 2023. Randomized controlled trials (RCTs) that evaluated the acupuncture's effects for women undergoing IVF were included. The subgroup analysis was conducted with respect to the age of participants, different acupuncture types, type of control, acupuncture timing, geographical origin of the study, whether or not repeated IVF failure, and acupuncture sessions. Sensitivity analyses were predefifined to explore the robustness of results. The primary outcomes were clinical pregnancy rate (CPR) and live birth rate (LBR), and the secondary outcomes were ongoing pregnancy rate and miscarriage rate. Random effects model with I² statistics were used to quantify heterogeneity. Publication bias was estimated by funnel plots and Egger's tests. RESULTS: A total of 58 eligible RCTs representing 10,968 women undergoing IVF for pregnant success were identifified. Pooled CPR and LBR showed a signifificant difference between acupuncture and control groups [69 comparisons, relative risk (RR) 1.19, 95% confifidence intervals (CI) 1.12 to 1.25, I²=0], extremely low evidence; 23 comparisons, RR 1.11, 95%CI 1.02 to 1.21, I²=14.6, low evidence, respectively). Only transcutaneous electrical acupoint stimulation showed a positive effect on both CPR (16 comparisons, RR 1.17, 95%CI 1.06 to 1.29; I²=0, moderate evidence) and LBR (9 comparisons, RR 1.20, 95%CI 1.04 to 1.37; I²=8.5, extremely low evidence). Heterogeneity across studies was found and no studies were graded as high-quality evidence. CONCLUSION Results showed that the convincing evidence levels on the associations between acupuncture and IVF pregnant outcomes were relatively low, and the varied methodological design and heterogeneity might inflfluence the fifindings. (Registration No. PROSPERO CRD42021232430).
Pregnancy ; Female ; Humans ; Live Birth ; Fertilization in Vitro/methods* ; Pregnancy Outcome ; Abortion, Spontaneous ; Acupuncture Therapy

Objective To investigate the protective effect of Echinococcus granulosus hydatid cyst fluid protein (HCFP) on ovalbumin (OVA)-induced allergic rhinitis (AR) in mice. Methods Twenty-four BALB/c mice at ages of 8 to 10 weeks, each weighing approximately 20 g, were randomly divided into four groups, including groups A (blank control group), B (blank intervention group), C (AR model group) and D (AR+HCFP intervention group), with 6 mice in each group. On days 0, 2, 4, 6, 8, 10 and 12, mice in groups A, B, C and D were injected with 200 μL sterile phosphate buffered saline (PBS), 200 μL sterile PBS containing 20 μg HCFP, 200 μL sterile PBS containing 50 μg OVA and 5 mg Al(OH)₃ gel, and 200 μL sterile PBS containing 50 μg OVA, 5 mg Al(OH)₃ gel and 20 μg HCFP, respectively. On days 14 to 20, mice in groups A, B, C and D were administered with 40 μL sterile PBS, 40 μL sterile PBS containing 20 μg HCFP, 40 μL sterile PBS containing 2 mg OVA and 40 μL sterile PBS containing 2 mg OVA and 20 μL HCFP by nasal drop, respectively. Mouse behavioral changes were observed and behavioral scores were estimated. The serum levels of interferon-γ (IFN-γ), interleukin-4 (IL-4), IL-5, IL-10, transforming growth factor-β (TGF-β) and OVA-specific IgE antibody (OVA-sIgE) were measured using enzyme-linked immunosorbent assay (ELISA), and the pathological changes of mouse nasal mucosa were observed by hematoxylin and eosin (HE) staining. Results The mean behavioral score was significantly greater in Group C (6.83 ± 0.50) than in groups A (1.17 ± 0.52) and B (1.33 ± 0.52) (P < 0.05), while a lower mean behavioral score was estimated in Group D (3.50 ± 0.50) than in Group C (P < 0.05). There were significant differences among the groups in terms of serum IFN-γ (F = 4.08, P < 0.05), IL-4 (F = 275.90, P < 0.05), IL-5 (F = 96.82, P < 0.05), IL-10 (F = 77.67, P < 0.05), TGF-β (F = 9.98, P < 0.05) and OVA-sIgE levels (F = 44.69, P < 0.05). The serum IFN-γ level was significantly lower in Group C than in groups A, B and C (P < 0.05), and the serum levels of IL-4, IL-5 and OVA-sIgE were significantly higher in Group C than in groups A, B and C (P < 0.05), while the serum IL-10 and TGF-β levels were significantly greater in Group D than in Group C (P < 0.05). Microscopy showed apparent loss of nasal mucosa cilia, increased number and enlargement of goblet cells, interstitial edema and submucous vascular dilation in Group C, while the pathological changes of nasal mucosa were alleviated in Group D relative to Group C. Conclusions E. granulosus HCFP has a protective activity against OVA-induced allergic rhinitis in mice.

Objective: The scientific community knows little about the long-term influence of coronavirus disease 2019 (COVID-19) on olfactory dysfunction (OD). With the COVID-19 pandemic ongoing worldwide, the risk of imported cases remains high. In China, it is necessary to understand OD in imported cases. Methods: A prospective follow-up design was adopted. A total of 11 self-reported patients with COVID-19 and OD from Xi'an No. 8 Hospital were followed between August 19, 2021, and December 12, 2021. Demographics, clinical characteristics, laboratory and radiological findings, and treatment outcomes were analyzed at admission. We surveyed the patients via telephone for recurrence and sequelae at the 1-, 6-, and 12-month follow-up. Results: Eleven patients with OD were enrolled; of these, 54.5% (6/11) had hyposmia and 45.5% (5/11) had anosmia. 63.6% (7/11) reported OD before or on the day of admission as their initial symptom; of these, 42.9% (3/7) described OD as the only symptom. All patients in the study received combined treatment with traditional Chinese medicine and Western medicine, and 72.7% (8/11) had partially or fully recovered at discharge. In terms of OD recovery at the 12-month follow-up, 45.5% (5/11) reported at least one sequela, 81.8% (9/11) had recovered completely, 18.2% (2/11) had recovered partially, and there were no recurrent cases. Conclusions Our data revealed that OD frequently presented as the initial or even the only symptom among imported cases. Most OD improvements occurred in the first 2 weeks after onset, and patients with COVID-19 and OD had favorable treatment outcomes during long-term follow-up. A better understanding of the pathogenesis and appropriate treatment of OD is needed to guide clinicians in the care of these patients.
COVID-19/complications* ; Follow-Up Studies ; Humans ; Olfaction Disorders/etiology* ; Pandemics ; Prospective Studies ; SARS-CoV-2

Objective: To investigate the relationship between the expression of four mismatch repair proteins (MLH1, MSH2, MSH6 and PMS2) and NTRK genetic fusions in colorectal cancer. Methods: The paraffin-embedded tissue blocks of 830 cases of colorectal cancer were collected at the Affiliated Drum Tower Hospital, Nanjing University Medical School, China, from 2015 to 2019. Immunohistochemical and fluorescence in situ hybridization(FISH) method were used respectively to detect the expression of mismatch repair proteins and the break-apart of NTRKs; and the relationship between the expression of mismatch repair proteins and the NTRK genetic fusions was analyzed. Results: The overall mismatch repair protein deficiency (dMMR) rate was 9.88% (82/830), the mismatch repair proteins proficiency (pMMR) rate was 90.12%(748/830). The total deficiency rate of MLH1 protein was 9.04% (75/830), hPMS2 protein deficiency rate was 9.04% (75/830), MSH2 protein deficiency rate was 2.53% (21/830), MSH6 protein deficiency rate was 4.10% (34/830), the deficiency rate of synchronous MLH1 and PMS2 were 8.67% (72/830) and the deficiency rate of synchronous MSH2 and MSH6 were 2.17% (18/830). The dMMR group was associated with tumor location, different histological subgroups, tumor differentiation, AJCC stage and N stage (P<0.05). There were six cases (7.32%) carrying NTRK fusion by FISH among the 82 cases of dMMR, but only seven cases (0.94%) carrying NTRK fusion among the 748 cases of PMMR. The NTRKs translocation by FISH in all 13 cases were further confirmed by next generation sequencing. Among the clinicopathological characteristics, only differentiation showed significant difference between NTRK fusion positive and negative groups (P<0.05). More importantly, NTRK fusion was enriched in dMMR group (7.32% vs. 0.94%). Conclusion: In dMMR colorectal cancer group, the prevalence of NTRK fusion is higher than that in pMMR group.
Colonic Neoplasms ; Colorectal Neoplasms/genetics* ; DNA Mismatch Repair/genetics* ; Humans ; In Situ Hybridization, Fluorescence ; Mismatch Repair Endonuclease PMS2/metabolism* ; MutL Protein Homolog 1/metabolism* ; MutS Homolog 2 Protein/metabolism*

Objective: To inhibit the stemness maintenance potential of endometrial cancer and increase the sensitivity of endometrial cancer side population cells to chemotherapy drugs by inducing extensive deSUMOylation modification of proteins. Methods: Flow cytometry was used to sort and culture CD133(+) CD44(+) KLE endometrial cancer cell clone spheres. Protein expression level of small ubiquitin-related modifier 1 (SUMO1) and two stemness maintenance genes of tumor side population cells, octamer binding transcription factor-4 (Oct4) and sex determining region Y-box2 (Sox2), were detected by western blotting method. Lentivirus-mediated Sentrin/SUMO-specific proteases 1 (SENP1) gene was stably transfected into KLE side population cells. Western blotting was used to detect the protein expressions of SENP1, SUMO1, Oct4 and Sox2. The clone formation rate was compared between KLE side population cells with or without SENP1 overexpression. Flow cytometry was applied to detect cell cycle changes. 3-(4, 5-Dimethylthiazole-2)-2, 5-diphenyl-tetrazolium bromide (MTT) experiment and flow cytometry apoptosis method were used to detect the chemosensitivity of the side population of endometrial cancer cells to cisplatin. Tumor-bearing mouse models of endometrial cancer were established to detect the effect of SENP1 overexpression on the chemotherapy sensitivity of cisplatin. Results: Compared with CD133(-)CD44(-) KLE cells, CD133(+) CD44(+) KLE side population cells could form clonal spheres and express higher levels of SUMO1, Oct4 and Sox2 proteins (P<0.05). Compared with KLE side population cells that were not transfected with SENP1 gene, the expression level of SENP1 protein in KLE side population cells overexpressing SUMO1、Oct4 and Sox2 were lower. The clonal sphere formation rate was reduced from (25.67±5.44)% to (7.46±1.42)%, and cell cycle shifted from G(0)/G(1) phase to G(2) phase. IC(50) of cisplatin decreased from (55.46±6.14) μg/ml to (11.55±3.12) μg/ml, and cell apoptosis rate increased from (9.76±2.09)% to (16.79±3.44)%. Overexpression of SENP1 could reduce the tumorigenesis rate of KLE side population cells in vivo and increase their chemotherapy sensitivity to cisplatin (P<0.05). Conclusion: Overexpression of SENP1 can induce protein deSUMOylation modification, inhibit the stemness maintenance potential of endometrial cancer side population cells, and enhance their chemotherapy sensitivity, which provides a new reference for gene therapy of endometrial cancer.
Animals ; Female ; Humans ; Mice ; Apoptosis ; Cell Line, Tumor ; Cisplatin/pharmacology* ; Cysteine Endopeptidases/metabolism* ; Endometrial Neoplasms/genetics* ; Side-Population Cells/pathology* ; Sumoylation

Objective: To explore the safety and feasibility of stereotactic radiation therapy (SBRT) strategy for irradiating porcine ventricular septum, see if can provide a preliminary experimental evidence for clinical SBRT in patients with hypertrophic obstructive cardiomyopathy (HOCM). Methods: Five male pigs (39-49 kg, 6 months old) were used in this study. Pigs were irradiated at doses of 25 Gy (n=2) or 40 Gy (n=3). Delineation of the target volume was achieved under the guidance of 3-dimensional CT image reconstruction, and SBRT was then performed on defined target volume of porcine ventricular septum. Blood biomarkers, electrocardiogram and echocardiography parameters were monitored before and after SBRT. Pathological examination (HE staining, Masson staining) was performed on the target and non-target myocardium at 6 months post SBRT. Results: SBRT was successful and all animals survived to the designed study endpoint (6 months) after SBRT. Serum cardiac troponin T (cTnT) level was significantly higher than the baseline level at 1 day post SBRT, and reduced at 1 week after SBRT, but was still higher than the baseline level(P<0.05). Serum N-terminal pro-B type natriuretic peptide (NT-proBNP) was also significantly increased at 1 day post SBRT (P<0.05) and returned to baseline level at 1 week post SBRT. The serum NT-proBNP level was (249±78), (594±37) and (234±46) pg/ml, respectively, and the cTnT was (14±7), (240±40) and (46±34) pg/ml, respectively at baseline, 1 day and 1 week after SBRT in the 40 Gy dose group. The serum NT-proBNP level was (184±20), (451±49) and (209±36) pg/ml, respectively, the cTnT values ​​were (9±1), (176±29) and (89±27) pg/ml, respectively at baseline, 1 day and 1 week after SBRT in the 25 Gy dose group. Both NT-proBNP and cTnT values tended to be higher post SBRT in the 40 Gy dose group as compared with the 25 Gy dose group, but the difference was not statistically significant (P>0.05). The left ventricular ejection fraction and the left ventricular end-diastolic diameter remained unchanged before and after SBRT (P>0.05). The interventricular septum thickness showed a decreasing trend at 6 months after SBRT, but the difference was not statistically significant ((9.54±0.24) mm vs. (9.82±8.00) mm, P>0.05). The flow velocity of the left ventricular outflow tract, and the valve function and morphology were not affected by SBRT. At 6 months after SBRT, HE staining revealed necrosis in the irradiated target area of ​​the myocardium in the 40 Gy dose group and the 25 Gy dose group, and the degree of necrosis in the irradiated interventricular septum was more obvious in the 40 Gy dose group as compared with the 25 Gy group. The combined histological analysis of the two groups showed that the necrotic area of ​​the irradiated target area accounted for (26±9)% of the entire interventricular septum area, which was higher than that of the non-irradiated area (0) (P<0.05). There was no damage or necrosis of myocardial tissue outside the target irradiation area in both groups. The results of Masson staining showed that the percentage area of myocardial fibrosis was significantly higher in the irradiated target area than non-irradiated area ((12.6±5.3)% vs. (2.5±0.8)%, P<0.05). Conclusion: SBRT is safe and feasible for irradiating porcine ventricular septum.
Animals ; Feasibility Studies ; Male ; Necrosis ; Radiosurgery/methods* ; Stroke Volume ; Swine ; Ventricular Function, Left ; Ventricular Septum