ObjectiveTo explore the syndromes and mechanisms of depression induced by maternal separation （MS） combined with chronic restraint stress （RS） in mice. MethodOn postnatal day 0 （PD0）， the offspring mice were randomized into a blank group （NC） and a modeling group. The mouse model of depression was established by MS+RS for 21 days. After removal of female mice on PD21， the modeled mice were randomized into model， Wenyang， Jieyu， Wenyang Jieyu， and fluoxetine groups， with 15 mice in each group. The sucrose preference， tail suspension， and open field tests were carried out to evaluate the anxiety and depression-like behavior in mice. Enzyme-linked immunosorbent assay was used to measure the adrenocorticotrophic hormone （ACTH） and corticosterone （CORT） levels in mouse plasma. High performance liquid chromatography-electrochemical detector was used to determine the content of monoamine neurotransmitters in the hippocampus. Real-time fluorescence quantitative polymerase chain reaction was employed to determine the mRNA levels of genes in the 5-hydroxytryptamine （5-HT） system， hypothalamic-pituitary-adrenal （HPA） axis， and brain-derived neurotrophic factor （BDNF） signaling pathway in the hippocampus. Immunohistochemistry was employed to determine the expression levels of proteins in the 5-HT system and HPA axis in the hippocampus. The Simple Western system was used to determine the protein levels of BDNF and tyrosine kinase receptor B （TrkB） in the hippocampus. ResultCompared with the NC group， the model group exhibited depression-like behavior， which was significantly relieved by Wenyang Jieyu prescription and fluoxetine. Compared with the NC group， the model group showed elevated levels of CORT and ACTH in the plasma （P<0.01）， which， however， were lowered by Wenyang Jieyu prescription and fluoxetine （P<0.05， P<0.01）. Compared with the NC group， the model group showed inhibited expression of neurotransmitters in the hippocampus （P<0.05， P<0.01）， while Wenyang Jieyu prescription and fluoxetine restored the expression of neurotransmitters （P<0.05， P<0.01）. Compared with NC group， the model group showed inhibition of the 5-HTergic nerve and abnormal activation of the HPA axis， and Wenyang Jieyu prescription and fluoxetine regulated the abnormal state of the 5-HTergic nerve and HPA axis. Compared with NC group， the modeling down-regulated the mRNA and protein levels of BDNF and TrkB in the hippocampus （P<0.05， P<0.01）， which， however， were recovered in Wenyang， Jieyu， Wenyang Jieyu， and fluoxetine groups （P<0.05， P<0.01）. ConclusionThe mouse model of depression induced by MS+RS may present the syndrome of Yang deficiency and liver depression. Wenyang Jieyu prescription may increase the content of hippocampal neurotransmitters by regulating the 5-HT system and the BDNF signaling pathway mediated by the HPA axis， thereby alleviating depression-like behavior in mice.

Objective To analyze the postoperative effect of probiotics combined with Peitu Shengjin moxibustion and cupping on adenomatous colorectal polyps (ACP).Methods Patients with ACP diagnosed and treated in Zhejiang Provincial Hospital of Traditional Chinese Medicine from August 2021 to May 2022 were recruited as study subjects,and were divided into control group(probiotics) and test group (probiotics combined with Peitu Shengjin moxibustion and cupping).The main outcome measure of this study was the 1-year recurrence rate of ACP.The secondary outcome measures were the treatment efficiency and the traditional Chinese medicine (TCM) syndrome scores at 4 weeks and 1 year after ACP surgery.Results The study finally included 199 patients,with 100 in the control group and 99 in the test group.The 1-year postoperative treatment efficiency of the test group was higher than that of the control group (P=0.012);the recurrence rate was lower than that of the control group (P<0.05).There was no statistically significant difference in the comparison of polyp size and number between the two groups of patients with recurrence (P>0.05).Before treatment,there was no statistically significant difference between the two groups in the comparison of stool habit score,stool nature score,blood in stool score,stool frequency score,abdominal pain score and total score (P>0.05).The stool habit score,stool nature score,stool blood score,stool frequency score,abdominal pain score and total score of the patients in both groups were significantly lower than those of the preoperative period at 4 weeks and 1 year after the operation (P<0.05).Stool habit score,stool nature score,stool blood score,stool frequency score,abdominal pain score and total score were lower in the test group than in the control group at 4 weeks and 1 year postoperatively (P<0.05).Conclusion Probiotics combined with Peitu Shengjin moxibustion and cupping can effectively improve the TCM syndrome scores after ACP surgery and reduce the recurrence rate of ACP.

Objective:To explore the effect of health management based on constitution identification in perimenopausal women.Methods:From November 2020 to April 2021, 244 perimenopausal women from Doumen Street, Yuecheng District, Shaoxing were selected as the research subject by convenience sampling method, and divided into the control group (121 cases) and the observation group (123 cases) according to their respective communities. The control group adopted routine health management, while the observation group implemented health management based on constitution identification on the basis of routine health management. Three months after intervention, the perimenopausal symptom scores between the two groups were compared. One year after intervention, the number of individuals with biased constitution and quality of life scores between the two groups were compared.Results:Three months after intervention, the scores of hot flashes, sweating, insomnia, dizziness, fatigue, muscle and joint pain, headache, palpitations, and total score of perimenopausal symptom of the observation group were lower than those of the control group, with statistically significant differences ( P<0.05). Three months after intervention, there were no significant differences in scores of paraesthesia, mood swings, depressive suspicion, skin ant sensation, sexual difficulties, urinary tract infection between the observation group and the control group ( P>0.05). One year after intervention, the number of individuals with biased constitution of the observation group was less than that of the control group, and the difference was statistically significant ( P<0.05). One year after intervention, the scores of physical health, mental health, social relationship, and total score of quality of life of the observation group were higher than those of the control group, and the differences were statistically significant ( P<0.05). One year after intervention, there was no statistically significant difference in the score of the surrounding environment between the observation group and the control group ( P>0.05) . Conclusions:Health management based on constitution identification can improve the perimenopausal symptoms of perimenopausal women, gradually change their biased constitution towards a calm constitution, and improve their quality of life.

ObjectiveTo predict the potential molecular mechanism of Erxian decoction in the treatment of anxiety disorder based on network pharmacology， and to verify the efficacy and mechanism using the animal model of maternal separation combined with restraint stress. MethodActive components and related targets of Erxian decoction were obtained by traditional Chinese medicine system pharmacology database and analysis platform （TCMSP） and SwissTargetPrediction. The targets related to anxiety disorder were screened out through GeneCards， therapeutic target database （TTD）， online mendelian inheritance in man database （OMIM）， and DrugBank， and the drug-disease intersection targets were obtained by taking intersections with the drug targets. The protein-protein interaction （PPI） network was constructed by the STRING database， and the core targets were screened out based on topological parameter analysis. Gene Ontology （GO） enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were carried out for the intersection targets through the Metascape platform. Maternal separation combined with restraint stress was used to induce the mouse model of anxiety disorder. From the end of lactation on the 21st postnatal day （PD21） to the completion of restraint stress on the 97^th postnatal day （PD97）， the mice were fed with Erxian decoction mixed with diet. The anxiety state of mice was evaluated by open field test and elevated O-maze test. The content of plasma corticosterone （CORT） in mice was detected by enzyme-linked immunosorbent assay （ELISA）. The expression levels of protein kinase B （Akt1）， mammalian target of rapamycin （mTOR）， brain-derived neurotrophic factor （BDNF）， postsynaptic density-95 （PSD95）， and synaptophysin in the hippocampus of mice were detected by Western blot and real-time quantitative polymerase chain reaction （Real-time PCR）. ResultNinty-seven active components and 227 action targets of Erxian decoction were obtained. There were 3 863 targets related to anxiety disorder， with 161 drug-disease intersection targets. Among these intersection targets， core targets such as Akt1， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， tumor necrosis factor （TNF）， and mTOR were presumedly closely related to anxiety disorder. The results of KEGG pathway analysis showed that Erxian decoction mainly treated anxiety disorder through phosphatidylinositol 3-kinase （PI3K）/Akt， mitogen-activated protein kinase （MAPK）， and neuroactive ligand-receptor interaction signaling pathways. The results of animal experiments showed that compared with the model group， the Erxian decoction group significantly increased the time of mice spent in the central zone and central crossing times and time spent in the opened arm and opened arm crossing times， with significantly increased expression levels of p-Akt1， p-mTOR， BDNF， PSD95， and synaptophysin （Syp）. ConclusionErxian decoction has the multi-target and multi-pathway characteristics in the treatment of anxiety disorder， and its mechanism may be related to the improvement of synaptic plasticity and neuroinflammation by affecting Akt1， IL-1β， IL-6， TNF， mTOR， and other core targets and modulating PI3K/Akt， MAPK， as well as neuroactive ligand-receptor interaction signal pathways.

ObjectiveTo predict the molecular mechanism of Erxian decoction and Wenshen prescription （modified Erxian decoction） in the treatment of depression based on network pharmacology and explore the feasibility of Wenshen prescription in the treatment of depression by comparing the efficacy and mechanism of the two decoctions based on a depression model induced by maternal separation combined with chronic restraint stress. MethodActive components and targets of Erxian decoction and Wenshen prescription were collected through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and Bioinformatics Analysis Tool for Molecular mechanism of Traditional Chinese Medicine （BATMAN-TCM）. Targets related to depression were screened out from databases such as GeneCards， Online Mendelian Inheritance in Man database （OMIM）， and DrugBank. Common targets of drugs and disease were obtained and imported to Cytoscape 3.8.2 to plot the drug-active component-target-disease network. STRING platform was used to construct a protein-protein interaction （PPI） network and core targets and related core components were screened out. Gene Ontology （GO） enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） functional enrichment analysis were performed on common targets through Metascape platform. The depression model was induced in mice by maternal separation combined with chronic restraint stress. From the 21st day of maternal separation （PD21） to the 111th day of restraint stress completion （PD111）， mice were fed with the diet mixed with Erxian decoction or Wenshen prescription for intervention. The depressive state of mice was evaluated according to the sucrose preference test， tail suspension test， open field test， and elevated O-maze test. The expression of ionized calcium-binding adapter molecule 1 （Iba1） in the microglia was observed by immunohistochemistry （IHC）. Western blot and Real-time fluorescence-based quantitative polymerase chain reaction （Real-time PCR） were used to detect the expression levels of protein kinase B1（Akt1）， brain-derived neurotrophic factor （BDNF）， postsynaptic density-95 （PSD95）， and synaptophysin （Syn）. ResultA total of 126 and 118 targets of Erxian decoction and Wenshen prescription in the treatment of depression were screened out， with only eight more targets of Erxian decoction than Wenshen prescription. The two decoctions shared the same core targets， mainly including Akt1， interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α）. KEGG pathway enrichment analysis predicted that Erxian decoction and Wenshen prescription mainly treated depression through the phosphatidylinositol-3 kinase （PI3K）/Akt signaling pathway， mitogen-activated protein kinase （MAPK） signaling pathway， and neuroactive ligand-receptor interaction pathway. Animal experiments showed that compared with the results in the model group， Erxian decoction and Wenshen prescription could up-regulate the sucrose preference index， prolong the time spent in the central zone， increase the number of crossings， prolong the time spent in opened arm， increase the number of crossings in the opened arm， elevate the expression levels of p-Akt1， BDNF， PSD95， and Syn （P<0.05， P<0.01）， shorten the immobility time of tail suspension， and reduce the expression level of Iba-1 in the hippocampal microglia （P<0.05， P<0.01）. No significant difference between the two decoctions was found. ConclusionUnder the pathogenesis and syndrome law of depression dominated by kidney yang deficiency， Wenshen prescription modified from Erxian decoction is feasible in the treatment of depression. The mechanism may be attributed to the fact that both decoctions can improve neuroinflammation and synaptic plasticity in the hippocampus by affecting Akt1， IL-1β， IL-6， TNF-α， and other core targets and regulating the PI3K/Akt， MAPK， and neuroactive ligand-receptor interaction signaling pathways.

ObjectiveTo observe the behavioral and pain threshold alterations， as well as the changes in indexes related to depression and pain in the serum and central system in mice stressed by maternal separation and chronic neuropathic pain， and explore the underlying mechanism of Wenyang prescription （WY）， Jieyu prescription （JY）， and Wenyang Jieyu prescription （WYJY） in improving depression and pain sensitivity. MethodThe birth date of mice was recorded as PD0. After birth， the mice were divided into a blank group and an experimental group. The neonatal mice in the experimental group underwent maternal separation in PD5-14 at 8 h·d^-1. After ablactation， the mice were divided into a maternal separation group， a WY group （Erxian decoction， 5.84 g·kg^-1）， a JY group （Xiaoyaosan， 12.00 g·kg^-1）， a WYJY group （16.68 g·kg^-1）， and a fluoxetine group （2.60 mg·kg^-1）， with 15 mice in each group. Meanwhile， 15 male mice of the same age without maternal separation were assigned to the normal control group. Mice in the blank group and the maternal separation group were fed on a regular chow diet in PD21-PD90， while the remaining groups were fed on the corresponding drugs. In PD91， sciatic nerve ligation was performed to induce a model of maternal separation and chronic neuropathic pain. The open field test was used to observe the depression-like behaviors of mice in each group， and the mechanical and temperature pain thresholds were measured to detect the pain sensitivity of mice in each group. The serum levels of corticosterone （CORT）， substance P， and β-endorphin （β-EP） were determined by enzyme-linked immunosorbent assay （ELISA）， and the expression of the glucocorticoid receptor （GR） in the amygdala and β-EP protein in the hypothalamus was detected by immunohistochemistry. The mRNA expression levels of amygdala GR gene （Nr3c1）， FK506 binding protein 5 gene （FKBP5）， metabolic glutamate receptor 5 gene （GRM5）， and brain-derived neurotrophic factor （BDNF） were detected by real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）. ResultCompared with the blank group， the maternal separation group showed reduced stay time and total distance traveled in the 5-min open field test （P<0.01）， reduced mechanical pain threshold （P<0.01）， increased serum CORT and β-EP （P<0.01）， declining FKBP5 mRNA expression （P<0.01）， and increased hypothalamic β-EP expression （P<0.05）. Compared with the maternal separation group， the groups with drug intervention showed prolonged stay time （P<0.05， P<0.01） and up-regulated pain thresholds to different degrees. The total distance traveled in the 5-min open field test increased in the WY group， the WYJY group， and the fluoxetine group （P<0.05， P<0.01）. The JY group showed decreased serum CORT （P<0.01）， reduced β-EP ， and increased BDNF mRNA （P<0.01）. Nr3c1 and GRM5 mRNA decreased in the WY group （P<0.05， P<0.01）. The WYJY group showed decreased serum CORT （P<0.05）and decreased Nr3c1， GRM5， and BDNF mRNA （P<0.05， P<0.01）. The levels of β-EP expression were elevated to different degrees in the groups with drug intervention， but the differences were not significant. The levels of GR expression in the WY group， the JY group， and the WYJY group increased （P<0.05）. ConclusionWYJY can inhibit central pain sensitization and regulate hypothalamic-pituitary-adrenal gland （HPA） axis function by enhancing the expression of GR in the amygdala and inhibiting neuroplasticity and excitability in the amygdala to relieve depression-like behaviors and improve somatic hyperalgesia.

Objective:To investigate the status and influencing factors of enteral nutrition support in late preterm infants (34-36 +6 gestational weeks) treated in different grades of hospitals in Beijing. Methods:This was a prospective study involving late preterm infants treated in 25 hospitals in Beijing from October 2015 to October 2017. Data about nutritional management and nutrition-related complications were recorded. Exclusive breastfeeding status of the infants by gestational age(GA) and hospital levels was analyzed. The achievement of full enteral feeding and the potential influencing factors were also analyzed. t-test, Mann-Whitney U test, analysis of variance (ANOVA), Kruskal-Wallis test and Chi-square test were used for statistical analysis. Logistic regression and Cox regression analysis were used in multivariate analysis. Results:(1) A total of 1 463 late preterm infants with GA of 35.6±0.8 (ranging from 34.9 to 36.1) weeks was enrolled in this study. Compared with the infants with GA of 35-35 +6 and 36-36 +6 weeks, those born at 34-34 +6 gestational weeks had longer hospital stay [10 (8-13) vs 8 (7-10) and 7 (6-9) d, both P<0.05], greater loss of minimum weight [4.3% (2.6%-6.3%) vs 3.8% (2.0%-5.6%) and 3.3% (1.9%-5.5%), both P<0.05], higher incidence of apnea [5.3% (20/369) vs 2.1% (12/566) and 1.3% (7/528), both P<0.05] and respiratory distress syndrome (RDS) [7.1% (28/369) vs 3.0% (17/566) and 3.2% (17/528), both P<0.05], and lower percentage of failure to regain birth weight at discharge [32.5% (120/369) vs 38.7% (219/566) and 47.9% (253/528), both P<0.05]. Only the incidence of premature rupture of membranes among all maternal complications during pregnancy had statistical difference between 34-34 +6, 35-35 +6 and 36-36 +6 GA groups [6.2% (23/369) vs 12.7% (72/566) and 11.9% (63/528), χ2=10.244, P=0.007]. (2) The rate of enteral feeding increment in hospital was 13.7 (10.5-17.3) ml/(kg·d) and 46.0% (673/1 463) of the infants were fed formula. The exclusive breastfeeding rate increased from 4.5% (66/1 463) during hospitalization to 14.4% (211/1 463) at discharge. The breastfeeding rate at discharge varied widely among the 25 hospitals ( χ2=327.893, P<0.001) ranging from 32% to 0. (3) Logistic regression analysis demonstrated that gestational diabetes mellitus ( OR=2.426, 95% CI: 1.075-5.437, P=0.033) and premature rupture of membranes ( OR=8.726, 95% CI: 1.193-63.802, P=0.033) were the prenatal risk factors influencing the exclusive breastfeeding in late preterm infants. Enteral nutrition achieving 150 ml/(kg·d) and 120 kcal/(kg·d) (1 kcal=4.184 kJ) were noted for 28.4% (416/1 463) and 19.2% (281/1 463) of the late preterm infants at discharge, respectively. Cox regression analysis showed that hospital grades ( HR=1.470, 95% CI: 1.030-2.098, P=0.034), the length of hospital stay ( HR=1.162, 95% CI: 1.097-1.231, P<0.001), birth weight ( HR=0.946, 95% CI: 0.898-0.995, P=0.003), exclusive breastfeeding ( HR=2.354, 95% CI:1.031-5.374, P=0.042), feeding intolerance ( HR=3.677, 95% CI: 1.201-11.253, P=0.023), parenteral nutrition ( HR=1.900, 95% CI: 1.379-2.616, P<0.001), and the rate of enteral feeding advancement ( HR=1.426, 95% CI: 1.369-1.484, P<0.001) were independent factors associated with full enteral feeding at discharge. Conclusions:Exclusive breastfeeding rate in late preterm infants is low and enteral nutrition support varies greatly in different hospitals. The rate of enteral feeding increment is slow for hospitalized late preterm infants and most fail to achieve full enteral feeding at discharge. Gestational diabetes mellitus and premature rupture of membranes are prenatal risk factors affecting breastfeeding of late preterm infants. Those with low birth weight, exclusive breastfeeding in hospital, feeding intolerance, parenteral nutrition support, longer hospital stay or rapid enteral feeding advancement are more likely to achieve full enteral feeding at discharge.

Objective:To study the clinical and pathologic factors of papillary thyroid microcarcinoma (PTMC) and its significance as a histopathologic subtype of papillary thyroid carcinoma (PTC).Methods:A retrospective study of 719 patients with non-high-risk PTMC who underwent surgery for the first time in the Peking University People′s Hospital from January 2007 to June 2019 was conducted, the relationship between clinicopathologic factors and lymph node metastasis, and the expression of four tumor markers CK19, HMBE1, Galectin-3 and CD56 by immunohistochemistry were evaluated. Some comparisons were made with PTC.Results:The peak patients′ age was 40-49 years for both non-high-risk PTMC and PTC; the lymph node metastasis rate was higher in the 30-39 years age group than the 50-59 years age group ( P<0.05); the lymph nodes metastasis rate was significantly higher for multiple lesions than for single lesion ( P<0.05). Lymph node metastasis rate of PTMC with capsular invasion was significantly higher than those without ( P<0.05). There was no significant correlation between lymph node metastasis of PTMC and patients′ gender, tumor location, tumor size, and lymphocytic thyroiditis. The expression rates of CK19, HMBE1 and Galectin-3 both in PTMC and PTC were 100%, and the expression rates of CD56 were 25.6% (85/332) and 20.0% (70/350) respectively. Conclusion:As the main pathologic subtype of PTC, a variety of clinicopathologic factors of PTMC are related to lymph node metastasis, and it is highly recommended to pay close attention to PTMC. The expression of tumor marker CD56 alone cannot be used as a basis to exclude PTMC and PTC.

Objective: To introduce the methods for sensitivity analysis, discuss and compare the advantages and disadvantages of different methods. Methods: The difference between confounding function method and bounding factor method in accuracy of identifying unmeasured confounding factors in observational studies through simulation trials and actual clinical data was compared. Results: The results of simulation trials and actual clinical data showed that when there was unmeasured confounding between exposure (X) and outcome (Y), the results of confounding function and the bounding factor analysis were similar in terms of the effect of unmeasured confounding factor to lead to the complete change of the magnitude and direction of the observed effect value. However, the confounding function method needed smaller confounding effect to fully interpret the observed effect value than the bounding factor needed. In addition, the bounding factor method needed to analyze two confounding parameters, while only one parameter was needed in the confounding function method. The confounding function method was simpler and more sensitive than the bounding factor method. Conclusion For real-world observational data, the sensitivity analysis process is essential in analyzing the causal effects between exposure (X) and outcome (Y). In terms of the calculation process and result interpretation the sensitivity analysis method of confounding function is worth to recommend.

Objective To study the clinicopathologic features,diagnosis and differential diagnosis of tumors of haematopoietic and lymphoid tissue in the female productive tract. Methods Eleven cases of myeloid sarcoma and leukemia, 9 of non Hodgkin lymphoma(NHL),13 of cervical lymphoma-like lesions were selected from Peking University People′s Hospital from January 2006 to August 2017. According to WHO classification of tumors of haematopoietic and lymphoid tissues(2008)and updated classification(2016),the cases were studied by microscopy,immunohistochemistry and in situ hybridization.Results In 20 cases of tumors of haematopoietic and lymphoid tissue,the mean and median age was 48.5 and 56 years old(range:16-77 years old).In cases of lymphoma-like lesion of uterine cervix,the mean and median age was 45.9 and 48 years old(range:23-62 years old).The patients with neoplasm present as fever,fatigue, hypogastralgia, colporrhagia and mass etc. Eight cases had history of acute myeloid leukemia, and 3 had myeloid leukemia while pregnancy. One case of chronic lymphocytic leukaemia/small lymphocytic lymphoma(CLL/SLL)had history of ovary small cell carcinoma and high grade serous carcinoma resected with chemotherapy.One case of diffuse large B cell lymphoma(DLBCL)had history of renal transplantation. Lactic dehydrogenase(LDH)was elevated in 9 cases(9/18).The cases of lymphoma-like lesion present as contact bleeding in most cases and all located in cervix. Four cases of neoplasm located in vulva, 1 in vagina,4 in cervix, 4 in uterine corpus, 8 in ovary and 2 in placenta.Clinical staging of NHL: 4 case was stageⅠ,1 case of stageⅢ,and 4 cases of stageⅣ.Pathological morphology:9 cases were myeloid sarcoma, 2 cases were placenta invaded by myeloid leukemia. Six cases were DLBCL, and 1 case was CLL/SLL, 1 case was mucosa associated lymphoid tissuse lymphoma(MALToma), and 1 case was anaplastic large cell lymphoma. Resected mass, chemotherapy was performed in tumors of haematopoietic and lymphoid tissue. Five cases of myeloid sarcoma and 2 of NHL died. In 13 cases of lymphoma-like lesion of uterine cervix, the general condition was good as following up. Conclusions The clinical history, pathological morphology and immunohistochemistry are very important for diagnosing tumors of haematopoietic and lymphoid tissue in the female productive tract.Resection with chemotherapy is recommended in treatment. The prognosis of lymphoma-like lesion of uterine cervix is good,and should be differentiated from lymphoma.