Objective To evaluate the efficacy and safety of dienogest in the conservative treatment of adenomyosis(AM).Methods The relevant randomized controlled trials were searched by computer from domestic and foreign electronic bibliographic databases to August 2023.Risk of bias tool was used to evaluate the literature quality,and RevMan 5.4 software was used for analysis.Results A total of 654 patients with AM were included in 9 randomized controlled trials.338 patients received dienogest for 3 to 6 months.Meta-analysis results showed that the total effective rate of dienogest in the treatment of adenomyosis(OR=6.70,95％CI:1.84-24.42,P=0.004)and serum carbohydrate antigen 125(CA125)reduction(MD=-6.89,95％CI:-12.84-0.93,P=0.02),uterine volume(MD=-26.49,95％CI:-37.86-15.12,P<0.00001),quality of life questionnaire score(MD=6.12,95％CI:4.76-7.47,P<0.00001),the difference was statistically significant.Pain improvement(MD=-0.14,95％CI:-2.19-1.92,P=0.90),endometrial thickness(MD=-0.54,95％CI:-3.66-2.59,P=0.74),the difference was not statistically significant.The overall incidence of adverse reactions(OR=0.51,95％CI:0.12-2.18,P=0.37)and the incidence of irregular vaginal bleeding(OR=1.98,95％CI:0.25-15.59,P=0.52),the difference was not statistically significant.Conclusion Dienogest improves overall response rates,reduces uterine volume in certain degree,relieves subjective symptoms,and improves quality of life in patients with adenomyosis.

[Objective]To explore the effect of Wenshen Xiaozheng Decoction on pain in mice with endometriosis(EMS)and its mechanism based on cyclooxyfenase-2/prostaglandin E2(COX-2/PGE2)signaling pathway.[Methods]Forty EMS mouse models were established by intraperitoneal injection as modeling group,which was randomly divided into EMS model group(0.2 mL sterile distilled water),Wenshen Xiaozheng Decoction group(0.2 mL Wenshen Xiaozheng Decoction),positive control group(0.2 mL aspirin suspension),and another 10 mice were set as sham operation group.During the 21 days of modeling,the Von Frey fiber test and hot plate test were used to detect mechanical and thermal pain in mice in modeling group and sham operation group.During the 21 days of administration,Von Frey fiber test and hot plate test were used to detect mechanical and thermal pain in EMS model group,Wenshen Xiaozheng Decoction group and positive control group.After 21 days of drug administration,vaginal smears were taken daily to determine the estrous cycle of the mice.During the same estrous cycle,mice were euthanized and serum,peritoneal fluid(PF),endometrial tissue(in situ endometrium,ectopic lesions),thalamus,spinal cord and dorsal root ganglion(DRG)were collected.Enzyme-linked immunosorbent assay(ELISA)was used to determine the contents of COX-2,PGE2,transient receptor potential vanilloid 1(TRPV1),sodium channel protein type 11 subunit alpha(SCN11A).[Results]Compared with sham operation group,after modeling the pain thresholds of the feet and abdomen of the mice decreased(P<0.05).Compared with EMS model group,the mice in Wenshen Xiaozheng Decoction group showed an increase in foot and abdominal pain thresholds after administration(P<0.05).Compared with EMS model group,the mice in Wenshen Xiaozheng Decoction group showed the expression levels of COX-2,PGE2 in serum,in situ endometrium,PF,nervous system(thalamus,spinal cord,DRG),TRPV1 in central nervous system(thalamus,spinal cord),and SCN11A in peripheral nervous system(DRG)decreased(P<0.05).Compared with positive control group,the expression of PGE2 levels in serum,ectopic lesions and spinal cord of the mice in Wenshen Xiaozheng Decoction group decreased after administration(P<0.05).[Conclusion]Wenshen Xiaozheng Decoction can alleviate pain in EMS model mice,and its mechanism may be related to inhibiting the overexpression of COX-2/PGE2 signaling pathway.

Objective To assess the feasibility of establishing a nude mouse model of endometriosis fibrosis of human origin and to determine whether endometrial mesenchymal stem cells are involved in inducing endometriosis fibrosis.Methods Four endometrial tissue specimens were collected and transplanted 1∶3 into 12 BABL/c nude mice by subcutaneous injection.The morphology and volume of the lesions were recorded.The nude mice were sacrificed on the 15th day after transplantation to observe the morphology of the lesions and their adhesion to the periphery of the abdominal wall.HE staining was used to judge the result of modelling,Masson staining was used to assess the extent of fibrosis,and immunofluorescence was used to track the role of endometrial mesenchymal stem cells in the fibrotic process of endometriosis.Results The volume of ectopic lesions in nude mice increased over time and showed restricted,vesicular-like changes.The tight adhesion of the lesions to the abdominal wall,endometrioid glands,and collagen fiber deposition were seen microscopically.The success rate of the modelling was 83.4%,and the collagen fiber volume fraction of the lesions was significantly higher after modelling(P＜0.01).Confocal imaging suggested that endometrial mesenchymal stem cells(SUSD2+)differentiated into myofibroblasts(α-SMA+)in vivo.Conclusions The nude mouse model established by human allogeneic transplantation via subcutaneous injection was consistent with the lesion characteristics of endometriosis fibrosis.The modelling method is simple and feasible and provides a better reference model for further investigating the pathogenesis of endometriosis fibrosis.In addition,in vivo observations using the model indicated that endometrial mesenchymal stem cells are involved in inducing the formation of endometriosis fibrosis.

Objective:To investigate the clinical characteristics and interventions associated with drug-induced anaphylaxis in the emergency infusion room.Methods:Bases on the adverse drug reaction database from the emergency medicine center of the First Affiliated Hospital of Nanjing Medical University, clinical data of patients who experienced drug-induced anaphylaxis in the emergency infusion room between November 2019 and November 2023 were collected, including gender, age, history of previous adverse drug reactions, allergy history, Charlson comorbidity index, medication details, information related to drug-induced anaphylaxis (onset time, clinical manifestations), interventions, outcomes, and follow-up. The clinical characteristics and interventions in these patients were analyzed.Results:During the study period, a total of 398 772 patients in the emergency infusion room in our hospital received intravenous infusion of drugs. Of them, 625 cases developed adverse drug reactions (ADRs) and 75 cases developed drug-induced anaphylaxis, accounting for 0.02% (75/398 772) of the total infusion patients and 12.0% (75/625) of all ADR cases. Of the 75 patients with anaphylaxis, 30 cases (40%) were classified as grade Ⅱ, and 45 cases (60%) as grade Ⅲ, with no grade Ⅳ cases. The most common drugs involved in 75 cases of anaphylaxis were anti-infective drugs (41 cases, 54.7%). Drug-induced anaphylaxis exhibited diverse clinical manifestations, with cardiovascular symptoms being the most common, primarily varying degrees of transient hypotension (67 cases, 89.3%), followed by systemic and neurological symptoms, including profuse sweating (31 cases, 41.3%) and dizziness (28 cases, 37.3%). All 75 patients with anaphylaxis were treated with measures such as discontinuation of medication, replacement of infusion sets, rapid assessment of circulation and respiration, and monitoring of vital signs, of which 65 (86.7%) received rapid intravenous infusion for volume expansion, 6 (8.0%) received intravenous injection of glucocorticoids, 3 (4.0%) received intramuscular injection of 0.5 mg epinephrine, and 2 (2.7%) received antihistamines. All 75 patients showed improvement in symptoms, and no sequelae or deaths were found.Conclusions:In the emergency infusion room, the severity of anaphylaxis is mainly grade Ⅱ and Ⅲ with a good prognosis after timely intervention. The treatment measures mainly focus on rapid intravenous infusion for volume expansion, and the use of epinephrine is relatively low.

Objective:To investigate the clinical characteristics and interventions associated with drug-induced anaphylaxis in the emergency infusion room.Methods:Bases on the adverse drug reaction database from the emergency medicine center of the First Affiliated Hospital of Nanjing Medical University, clinical data of patients who experienced drug-induced anaphylaxis in the emergency infusion room between November 2019 and November 2023 were collected, including gender, age, history of previous adverse drug reactions, allergy history, Charlson comorbidity index, medication details, information related to drug-induced anaphylaxis (onset time, clinical manifestations), interventions, outcomes, and follow-up. The clinical characteristics and interventions in these patients were analyzed.Results:During the study period, a total of 398 772 patients in the emergency infusion room in our hospital received intravenous infusion of drugs. Of them, 625 cases developed adverse drug reactions (ADRs) and 75 cases developed drug-induced anaphylaxis, accounting for 0.02% (75/398 772) of the total infusion patients and 12.0% (75/625) of all ADR cases. Of the 75 patients with anaphylaxis, 30 cases (40%) were classified as grade Ⅱ, and 45 cases (60%) as grade Ⅲ, with no grade Ⅳ cases. The most common drugs involved in 75 cases of anaphylaxis were anti-infective drugs (41 cases, 54.7%). Drug-induced anaphylaxis exhibited diverse clinical manifestations, with cardiovascular symptoms being the most common, primarily varying degrees of transient hypotension (67 cases, 89.3%), followed by systemic and neurological symptoms, including profuse sweating (31 cases, 41.3%) and dizziness (28 cases, 37.3%). All 75 patients with anaphylaxis were treated with measures such as discontinuation of medication, replacement of infusion sets, rapid assessment of circulation and respiration, and monitoring of vital signs, of which 65 (86.7%) received rapid intravenous infusion for volume expansion, 6 (8.0%) received intravenous injection of glucocorticoids, 3 (4.0%) received intramuscular injection of 0.5 mg epinephrine, and 2 (2.7%) received antihistamines. All 75 patients showed improvement in symptoms, and no sequelae or deaths were found.Conclusions:In the emergency infusion room, the severity of anaphylaxis is mainly grade Ⅱ and Ⅲ with a good prognosis after timely intervention. The treatment measures mainly focus on rapid intravenous infusion for volume expansion, and the use of epinephrine is relatively low.

Objective Small cell neuroendocrine carcinoma of the ovary is a kind of ovarian cancer with a very low incidence.Its clinical manifestations are not obvious.The diagnosis should be based on the pathology and neuroendocrine indicators, and its primary nature should be determined.The main treatment is operation combined with platinum based chemotherapy.The survival period is related to clinical stage and treatment plan.The patient was hospitalized for 2 days because of the aggravation of abdominal distention and pain for half a year.The diagnosis of adnexal mass was confirmed by pathology.After three cycles of neoadjuvant chemotherapy (etoposide+ cisplatin), the patients underwent abdominal " total hysterectomy+ greater omentum resection+ appendectomy+ right pelvic wall peritoneal biopsy+ mesenteric biopsy" . After the operation, the patients received three cycles of EP chemotherapy, and they have been followed up for 15 months.

Objective To investigate the relationship between fibrosis and M2 macrophages in endometriosis. Methods BALB/c mice model of endometriosis was established by intraperitoneal injection. The growth of ectopic lesions in mice was observed on the 7th,14th and 21th day after modeling. Masson staining was used to observe the degree of fibrosis and immunohistochemical method to detect the expression of CD206 and CD68 of mice. Image-Pro-Plus 6.0 was used for semi quantitative analysis of staining and the correlation between the degree of fibrosis and the expression of M2 macrophages was explored. Results The success rate of the establishment of endometriosis model by intraperitoneal injection was 100%. There was a positive correlation between fibrosis and the expression of M2 macrophages in endometriosis mice model. Conclusions The mice model of endometriosis can be established successfully by intraperitoneal injection and M2macrophages may promote fibrosis in endometriosis.

By reviewing the reports of clinical study on herbs of promoting the circulation of Qi to remove blood stasis in treating adenomyosis in recent years, therapeutic mechanism and clinical effects of the treatment were summed up, in order to provide literature reference for the therapy.

Objective To investigate the effects of miR-135a on HOXA10 expression,proliferation and apoptosis of SKOV3 cells.Methods (1) Through computer-aided algorithms,the predicted target gene of miR-135a (HOXA10)were determined.(2) miR-135a mimics,miR-135a inhibitor and negative control were transfected into SKOV3 cells,respectively.Reverse transcription (RT)-PCR,western blot analysis were used to examine the expression levels of HOXA10 at different times (24,48 and 72 hours).(3) A luciferase reporter assay was used to confirm the direct regulation between miR-135a and HOXA10.(4) SKOV3 cells proliferation at different times (24,48 and 72 hours) was detected by methyl thiazolyl tetrazolium(MTT) assay [quantified by absorbance(A)].Western blot was used to examine the expression of apoptosis-associated protein bcl-2,bax and caspase-3 in SKOV3 cells after 48 hours transfection.Results (1) HOXA10 was predicted to be the target gene of miR-135a by computer-aided algorithms.(2) RT-PCR shown that HOXA10 mRNA levels were decreased over time (24,48 and 72 hours) after miR-135a mimics transfectionin SKOV3 cells (0.94 ±0.04 vs 0.78 ±0.03 vs 0.70 ±0.03,P ＜0.05).While,the expression of HOXA10 mRNA was increased over time after miR-135a inhibitor transfection (1.14 ± 0.05 vs 1.16 ±0.03 vs 2.60 ±0.08,P ＜0.05).After transfected with miR-135a mimics or miR-135a inhibitor over 48 and 72 hours,the HOXA10 expression levels in SKOV3 cells were significantly lower or higher than each control group,respectively (all P ＜ 0.01).Western blot analysis of HOXA10 expression in SKOV3 cells confirmed the results of RT-PCR detected.(3) After cotransfection of miR-135a plasmid and pMIR-REPORT luciferase plasmid containing HOXA10,luciferase reporter assays showed that the luciferase activity reduced by 67.8％ (P ＜0.01).(4) MTT showed that SKOV3 cells growth after miR-135a mimics transfection for 48 and 72 hours were significantly lower than those in control group (0.38 ± 0.03 vs 0.52 ± 0.05,0.67 ±0.05 vs 0.75 ± 0.06 ; respectively,all P ＜ 0.05).While,SKOV3 cells transfected with miR-135a inhibitor for 72 hours grew significantly faster than that in control group (0.95 ± 0.05 vs 0.75 ± 0.06,P ＜ 0.01).After miR-135a mimics transfection,the level of bcl-2 protein was significantly lower than that in control group (0.28 ±0.06 vs 0.76 ±0.09,P ＜0.01).The activity of caspase-3 was significantly higher than that in control group (115.0 ± 2.4 vs 95.4 ± 2.1,P ＜ 0.01).While,there was no statistical difference of bax expression (P =0.142).However,after miR-135a inhibitor transfection,the expression level of bcl-2 protein was significantly higher than that in control group (0.92 ± 0.03 vs 0.76 ± 0.09,P =0.037) and the activity of caspase-3 was significantly lower than that in control group (59.5 ± 4.1 vs 95.4 ± 2.1,P ＜ 0.01).There was also no statistical difference of bax expression (P =0.066).Conclusion miR-135a may play an important role in cell proliferation and apoptosis of ovarian cancer cells by regulating HOXA10 and its downstream pathways.

The activity of matrix metalloproteinases (MMPs) in the uterine flushing and endometrial tissue of normal adult women wearing FCu-IUD (fixed Cu-IUD) or FICu-IUD (indomethacin-releasing FCu-IUD) was observed by using zymography on SDS-PAGE containing gelatin. The results showed that the activity and kinds of MMPs in FCu-IUD group were increased significantly as compared with themselves before being inserted FCu-IUD. However, compared with the FCu-IUD group, the activity of some kinds of MMPs in the FICu-IUD group was decreased significantly. These data suggest that IUD can enhance the activity of MMPs in human endometrium, intermediated by prostaglandins, and MMPs may have relation to IUD-induced menorrhagia and indomethacin reduces IUD-induced menorrhagia by partly inhibiting MMPs synthesis.
Adult ; Endometrium ; enzymology ; Female ; Humans ; Indomethacin ; Intrauterine Devices, Copper ; adverse effects ; Intrauterine Devices, Medicated ; adverse effects ; Matrix Metalloproteinases ; metabolism ; Middle Aged ; Uterine Hemorrhage ; etiology ; prevention & control