ObjectiveThe research focuses on developing modeling and evaluation methodologies for an animal model exhibiting spleen deficiency and dampness excess syndrome， with the aim of standardizing such animal models for future reference. MethodsBy conducting a literature search on animal models of spleen deficiency and dampness excess syndrome， relevant publications meeting inclusion and exclusion criteria will be identified based on publication date， data source， types of diseases involved， animal characteristics， modeling methods， modeling duration， macroscopic syndrome assessment indicators， macroscopic quantification indicators， laboratory testing parameters， intervention approaches， positive controls and application context. A database will be established to facilitate the extraction of this information for quantitative analysis， statistical evaluation， and visual representation. ResultsA total of 137 literature articles meeting the standards have been included in the research. The primary animal species used in animal models of spleen deficiency and dampness excess are SD rats. Modeling methods include single-factor， dual-factor composite， and triple-factor composite methods， with various models widely applied in validation of pharmacological effects and mechanistic explorations. Evaluation indices of animal models for spleen deficiency and dampness excess primarily consist of macroscopic syndrome evaluation indicators and macroscopic quantitative indicators. Laboratory testing indicators are mostly related to research areas such as fluid metabolism and gastrointestinal function. The most commonly studied herbal formulas currently include Shenling Baizhu San and Pingwei San， with natural recovery and the use of the western medicine metronidazole as the most frequently used positive controls. ConclusionThe application of animal models for spleen deficiency and dampness excess is gradually increasing， with various modeling methods already simulating the typical characteristics of this syndrome pattern. However， there are still many areas that are worth contemplating and improving. This study aims to provide reference and ideas for the standardization of symptom names in animal models of spleen deficiency and dampness excess， as well as for the improvement of model construction and evaluation systems.

Objective: We aimed to investigate the differences of transcriptome profile between 2 groups of high-grade serous ovarian cancer (HGSOC) patients with distinct outcomes and identify potential biomarkers for recurrence. Methods: RNA sequencing was performed in 2 groups of HGSOC patients with similar demographic characteristics but exhibiting distinct progression-free survival (PFS). Transcriptome data of poor response (PR; PFS ≤6 months) and good response (GR; PFS ≥12 months) group were compared. We employed xCell to evaluate the abundance of 63 cells in tumor microenvironment. The predictive value of recurrence-related tumor infiltration cells was validated in cohort data from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) dataset. The weighted correlation network analysis was performed to identify the genes related to cell infiltration. Results: PR patients exhibited a distinct tumor infiltration immune cells-related transcriptional profile compared to GR patients, such as lower signatures of leukocyte differentiation, activation and chemotaxis. The fraction of T-helper 2 (Th2) cells infiltration was significantly higher in PR group than in GR group. High infiltration of Th2 was significantly associated with unfavorable prognosis in the GEO cohort (area under the curve=0.84 at 6 months recurrence) and TCGA cohort (p=0.008). Genes enriched to extracellular matrix organization and integrin binding were relevant to Th2 infiltration. Conclusion Patients with HGSOC having shorter PFS exhibited a distinct gene signature that related to tumor-infiltrating immune cells. The level of Th2 infiltration could facilitate patient recurrence risk stratification and may be a promising biomarker for prognosis prediction and immune-related treatment.

Objective: To investigate the clinical characteristics, treatments, and prognostic factors among patients with gestational trophoblastic neoplasia (GTN) exhibiting brain metastases who underwent craniotomy. Methods: Thirty-five patients with GTN who had brain metastases and subsequently underwent craniotomies between January 1990 and December 2018 at Peking Union Medical College Hospital were identified using the GTN database. Their clinical manifestations, treatments, outcomes, and prognostic factors were retrospectively analyzed. Results: All 35 patients underwent decompressive craniotomy, hematoma removal, and metastatic tumor resection combined with multiagent chemotherapy. Eighty percent (28/35) achieved complete remission, 11.4% (4/35) achieved partial remission, and 8.6% (3/35) had progressive disease. Not counting 2 patients who were lost to follow-up, 81.8% of the patients (27/33) were alive after a median follow-up of 72 months. The 5-year overall survival rate was 80.4%. Univariate analysis revealed that a history of chemotherapy failure (p=0.020) and a >1-week interval between craniotomy and chemotherapy commencement (p=0.027) were adverse risk factors for survival. Multivariate analysis showed that previous chemotherapy failure remained an independent risk factor for poor survival (odds ratio=11.50; 95% confidence interval=1.55–85.15; p=0.017). Conclusion Decompressive craniotomy is a life-saving option if metastatic hemorrhage and intracranial hypertension produce a risk of cerebral hernia in patients with GTN who have brain metastases. Higher survival rates and improved prognoses can be achieved through perioperative multidisciplinary cooperation and timely standard postoperative chemotherapy.

Objective:To investigate the therapeutic effect of programmed cell death receptor 1 (PD-1) inhibitor in drug-resistant recurrent gestational trophoblastic neoplasia (GTN).Methods:Clinicopathological features, previous treatments, PD-1 inhibitor treatment and prognosis of 8 patients with drug-resistant recurrent GTN treated with PD-1 inhibitor pembrolizumab， in Peking Union Medical College Hospital of Chinese Academy of Medical Sciences from August 2018 to June 2019 were collected and retrospectively analyzed.Results:(1) Clinicopathological features: the average age of onset of 8 GTN patients was 32.9 years old (31-39 years old); pathological types: choriocarcinoma in 7 cases, epithelioid trophoblastic tumor in 1 case. International Federation of Gynecology and Obstetrics (FIGO) stages: stage Ⅲ in 5 cases, stage Ⅳ in 3 cases; FIGO score: 4 patients with 7-12 points (high-risk group) and 4 patients with ≥13 points (ultra high-risk group). All the 8 patients had lung metastasis, 2 patients with brain metastasis, 1 patient with kidney and 1 patient with intestinal metastasis. (2) Previous treatments: ① Chemotherapy: 8 patients with GTN received an average of 21.1 courses (5-30 courses) of chemotherapy; the main route was systemic intravenous chemotherapy. One patient received intrathecal methotrexate chemotherapy due to brain metastasis. ② Surgery: 7 of 8 patients with GTN received surgical treatment, including 5 cases of pelvic surgury, 6 cases of pulmonary lobectomy and 1 case of right hemicolectomy. ③ Radiotherapy: 2 of 8 patients with GTN received radiotherapy, among which 1 patient received radiotherapy for lung for 8 times due to lung metastasis, and the other one received radiotherapy for lung, right sacroiliac joint and skull for a total of 22 times. (3) PD-1 inhibitor treatment: 8 patients with GTN received PD-1 inhibitor treatment with a mean course of 9 (2-12 courses). Six patients appeared Ⅰ-Ⅱ grade of immune related adverse events (AE), and no severe AE occurred. (4) Prognosis: after 2-3 courses of PD-1 inhibitor treatment, serum β-hCG level came to normalization in 4 patients. They were followed up for 2-7 months without any recurrence after 0-9 courses of consolidation treatment. One patient received 12 courses of PD-1 inhibitor treatment. The serum β-hCG level normalized after the 6th courses but increased 1 months later, and then received bevacizumab treatment due to the progression of the disease. The remaining 3 patients received other chemotherapy regiments due to disease progression during PD-1 inhibitor treatment.Conclusions:PD-1 could be used as a remedial treatment for drug-resistant recurrent GTN, with a high effective rate and relatively mild AE. However, more cases need to be accumulated clinically and efficacy should be comprehensively evaluated in combination with pathology and immunohistochemical examination.

Objective: To determine the effect of gut microbiota on a rat model of post-traumatic stress disorder(PTSD)and explore the correlation of gut microbiota with behavior and neurotransmitters.Methods: We established a single prolonged stress(SPS)model to examine the pathogenesis of PTSD on rat behavior,gut microbiota,and neurotransmitter levels.Rats were separated into control and model groups,and neurotransmitter levels were measured using enzyme linked immunosorbent assay.Then,16 S rRNA sequencing was used to compare the gut microbiota between the control and model groups.Results: Compared with those in the control group,freezing time significantly increased,while number of standing upright,crossing frequency,time spent in the central arena,and total distance traveled were significantly reduced in the model group after exposure to SPS(all P<.05).Meanwhile,serotonin,or 5-hydroxytryptamine,levels in the brain in the model group were significantly lower than those the control group(P=.0332).In addition,changes were observed in the gut microbiota diversity and relative abundances of bacterial phyla,orders,families,and genera in the model group.Especially,changes in Firmicutes,Bacteroidetes,Cyanobacteria,and Proteobacteria levels were most pronounced after SPS exposure.Correlation analysis showed that the strongest positive correlation was found between Bac-teroidaceae and 5-HT(P =.0009).Moreover,RF32 abundance was the most negatively related to 5-HT(P=.0009),crossing frequency(P=.0007),and total distance(P=.0003).Conclusion: Our results suggest that SPS model rats showed differences in behavior,neurotransmitter levels,and gut microbiota with control rats.Moreover,Firmicutes,Bacteroidetes,Cyanobacteria,and Proteobacteria were most relevant to the exhibited fear-like and anxiety-like behaviors and significant serotonin content reduction in SPS model rats.

OBJECTIVE: This study aims to evaluate the effects and pregnancy outcomes of gonadotropin-releasing hormone agonist (GnRH agonist) combined with aromatase inhibitor (AI) in preserving the fertility of obese women with grade 1 endometrial cancer (EC). METHODS: This study recruited obese EC patients who wished to preserve their fertility. The treatment regimen consisted of intramuscular GnRH agonist 3.75 mg every 4 weeks and oral AI 2.5 mg daily. The maintenance regimen was the same as the initial treatment regimen. Primary outcomes included response rate, time to complete response (CR), and time to recurrence; pregnancy outcomes included the time to pregnancy, pregnancy rate and live birth rate. RESULTS: Six obese patients with EC were included in this study, with the age (mean±standard deviation [SD]) of 30.5±3.3 years and body mass index (mean±SD) of 35.0±1.4 kg/m2. CR rate was 100%, and time to CR was 3–6 months. None of the patients had recurrence after a median follow-up of 4.0 years (range, 1.3–7.0 years). The most common side effects were menopause-like symptoms. Among these patients, no weight gain was observed during treatment. The pregnancy rate and live birth rate was 50.0% and 75.0%, respectively, with a median time to pregnancy of 2.4 years (range, 1.0–5.5 years). CONCLUSION: The combination of GnRH agonist and AI demonstrated promising long-term effect in young obese EC patients who wished to preserve their fertility. No weight gain side effects were observed. Further studies with a larger sample size are needed to fully evaluate this novel treatment regimen.
Aromatase Inhibitors ; Aromatase ; Body Mass Index ; Endometrial Neoplasms ; Female ; Fertility ; Follow-Up Studies ; Gonadotropin-Releasing Hormone ; Humans ; Live Birth ; Obesity ; Organ Sparing Treatments ; Pilot Projects ; Pregnancy ; Pregnancy Outcome ; Pregnancy Rate ; Recurrence ; Sample Size ; Time-to-Pregnancy ; Weight Gain

Objective To summarize and analyze the clinical outcomes of gestational trophoblastic neoplasia (GTN) patients receiving primary treatment at Peking Union Medical College Hospital from 1985 to 2015,and investigate the changes in treatment efficacy between the first and the second 15 years.Methods Clinical data of GTN patient receiving primary chemotherapy at Peking Union Medical College Hospital from January 1985 to December 2015 were retrospectively analyzed.It further compared the therapeutic results and chemotherapy cycles given to GTN patients,according to International Federation of Gynecology and Obstetrics (FIGO,2000) prognostic score system,who were classified to different stages and low-or high-risk groups.Results In total,1 711 GTN patients were included in this study.Comparing the 1985-2000 group and the 2001-2015 group,the results showed that:(1) while the overall complete remission (CR) rate was 93.7％ (1 603/1 711),the CR rate of 2001-2015 group was significantly higher than that of 1985-2000 group [98.4％ (1 155/1 174) vs 83.4％ (448/537),x2=139.353,P＜0.01].This difference was significant between stage Ⅲ and Ⅳ patients,but nonexistent between stage Ⅰ and Ⅱ patients,including low-and high-risk groups.(2) The relapse rate of patients who had been in CR was 2.7％ (43/1 603),with no significant differences between the groups of 1985-2001 and 2001-2015 [3.6％ (16/448) vs 2.3％ (27/1 155),x2=6.867,P=0.142].(3) The overall mortality rate was 2.6％ (44/1 711),which significantly decreased in 2001-2015 group compared to 1985-2000 group [1.6％ (19/1 174) vs 4.7％ (25/537),x2=13.830,P＜0.01].This difference appeared only in high-risk patients with stage Ⅲ disease (x2=9.505,P＜0.01).(4) Fluorouracil was gradually replaced by floxridine in chemotherapy regimens.The total cycles of chemotherapy regimens given to low-risk patients with stage Ⅲ disease significantly decreased in 2001-2015 group,but no statistical difference was shown with patients at other stages.Moreover,the cycles of consolidation treatment were significantly reduced in patients with stage Ⅲ patients.Conclusions GTN patients could obtain satisfactory curative results after appropriate and standard treatment.Peking Union Medical College Hospital has achieved better curative effect in the latest 15 years than before.

Objective Using a questionnaire to evaluate different regimens of chemotherapy on ovarian function and quality of life of patients with gestational trophoblastic neoplasia (GTN).Methods At least 6 months after completion of chemotherapy,200 patients with GTN treated in Peking Union Medical College Hospital from January 2010 to June 2017 were randomly selected to fill up the questionnaire.The questionnaire items were included the patient's menstrual cycles,sexual life,gestational issues and common health.The patients were divided into 3 groups by chemotherapy regimens:actinomycin D (Act-D) group,floxuridine + Act-D + vincristine (FAV) or floxuridine + Act-D + etoposide + vincristine (FAEV) group (FAV-FAEV group),and etoposide + methotrexate + Act-D (EMA)/vincristine + cyclophosphamide (CO) or EMA/ etoposide + cisplatin (EP) group (EMA/CO-EMA/EP group).Chi-square test was used with a significance level of P-value less than 0.05.Results One hundred and seventy-three (86.5％,173/200) of the patients completed the questionnaire.Forty three point two percent (43.2％,19/44) in the EMA/CO-EMA/EP group had a normal menstrual cycle,which were significantly lower than those of Act-D group (84.6％,22/26) and FAV-FAEV group (71.2％,37/52;all P＜O.05).Amenorrhea rate was also significantly higher in EMA/CO-EMA/EP group (25.0％,11/44) than in Act-D group(0) and FAV-FAEV group (17.3％,9/52;all P＜0.05).The sexual life parameters were comparable among 3 groups.Ten out of thirty-two patients conceived after chemotherapy,2 had miscarriages and 8 had full-term delivery of healthy babies.The common health and labor capacity were significantly decreased after chemotherapy (all P＜0.05).Conclusions EMA/CO or EMA/EP regimen have a worse impact on ovarian function than Act-D and FAV or FAEV regimen.Gynecologic oncologist should be concerned about the ovarian function and quality of life of GTN patients.

Objective To discuss the effects of prophylactic chemotherapy on the outcomes and prognosis of invasive mole patients.Methods One hundred and fifteen invasive mole (IM) patients older than 40 years were registered in Peking Union Medical Collage Hospital.Eleven of them were treated with prophylactic chemotherapy before diagnosed as IM prophylactic chemotherapy group,while the other 104 cases received therapeutic chemotherapy after diagnosed as IM (non-prophylactic chemotherapy group).The general clinical data (including age,clinical stage,risk factor score),treatment,outcomes and relapse of patients were retrospectively compared between two groups.Results (1) The age of prophylactic chemotherapy group and non-prophylactic chemotherapy group were (47±5) versus (46±4) years old.Ratio of clinical stage Ⅰ-Ⅱ were 3/11 versus 29.8％ (31/104),clinical stage Ⅲ-Ⅳ were 8/11 versus 70.2％ (73/104).Ratio of risk factor score 0-6 were 11/11 versus 84.6％ (88/104),risk factor score ＞6 were 0 versus 15.4％(16/104).There were no significant statistical differences between two groups in age,clinical stage or risk factor score (all P＞0.05).(2) Treatment:the total chemotherapy courses between prophylactic chemotherapy group and non-prophylactic chemotherapy group (median 7 versus 5) were significantly different (Z=3.071,P=0.002).There were no significant statistical differences between two groups in the chemotherapy courses until negative conversion of β-hCG,consolidation chemotherapy courses,total therapeutic chemotherapy courses or ratio of hysterectomy (all P＞0.05).(3) Outcomes and relapse:between the prophylactic chemotherapy group and the non-prophylactic chemotherapy group,the complete remission rate were 11/11 versus 98.1％(102/104),the relapse rate were 0 versus 1.0％(1/102).There were no significant difference between the two groups in outcomes or relapse rate (P＞0.05).Conclusions Prophylactic chemotherapy does not substantially benefit the IM patients older than 40 years.Prophylactic chemotherapy may not significantly improve patients' prognosis,in which increased sample size is required in further study.

Objective To investigate and analyze TCM syndrome characteristics, impact factors and internal relationship among the factors of mental fatigue of university students. A preliminary understanding of mental fatigue situation of university students and prevent diseases was acquired in advance. Methods 100 students were randomly selected in Beijing University of Chinese Medicine, of whom 40 were undergraduate students and 60 were post-graduate students. Mental fatigue questionnaire was used to investigate mental fatigue situation for students, and TCM constitution scale was applied to collect TCM syndromes. A body energy survey was also conducted. Results In undergraduate and post-graduate students, the mental fatigue rate was relatively higher, both of them were over 50%of the total numbers, 57.5%(23/40)、61.7%(37/60) respectively. For the fatigue levels distribution in these two groups, the ratios of slight mental fatigue (undergraduate:52.5%;post-graduate:56.67%) were both higher than those of severe mental fatigue (undergraduate:5%;post-graduate:5%). In the undergraduate group, the top three biased constitutions among mental fatigue students were yang deficiency (7 out of 23:30.43%), qi deficiency (3 out of 23:13.04%) and dampness-heat (3 out of 23:13.04%). In the post-graduate group, the top three biased constitutions were yang deficiency (11 out of 37:29.73%), qi deficiency (6 out of 37: 16.22%) and dampness-heat (5 out of 37: 13.51%). Conclusion It is easier for university students with biased constitution to suffer from mental fatigue, mostly with yang deficiency, qi deficiency and dampness-heat constitution.