Abstract:Antiphospholipid syndrome (APS) is an autoimmune disease affecting multiple organs and systems. The combination of APS with maternal hemodynamic changes during pregnancy can put the body in a hypercoagulable state, making it highly susceptible to placental thrombosis. In addition, the effect of antiphospholipid antibody (aPL) on trophoblast cell function can cause preeclampsia, fetal growth restriction, intrauterine fetal death, and other adverse outcomes. It is called obstetric antiphospholipid syndrome (OAPS) when patients with APS develop obstetric complications. This article provides a literature review on the diagnosis and staging of OAPS, the correlation with adverse pregnancy outcomes, the current status of diagnosis and treatment, and long-term follow-up, with the aim of providing guidance for clinical work.

Abstract:Aspirin is a cyclooxygenase inhibitor with anti-inflammatory and anti-platelet properties. As indicated by several national guidelines, low-dose aspirin (LDA) use in obstetrics and assisted reproduction has recently increased, particularly for the prevention of preeclampsia. At the same time, LDA can effectively improve the placental hypoperfusion by inhibiting the activity of cyclooxyge-nase to exert the effect of anti-platelet aggregation, and its indications for fetal growth restriction, preterm birth, obstetric antiphospholipid syndrome, assisted reproductive technology, and other conditions have been gradually expanded. This article reviews the recommendations and research progress of various guidelines on the application of low-dose aspirin in obstetrics and assisted reproduction.

Abstract:Cesarean scar pregnancy (CSP) is a special ectopic pregnancy, which mainly shows that the gestational sac and/or placenta are implanted in the scar of the previous cesarean section (limited to gestational weeks≤12 weeks). With the progress of medical imaging, CSP is becoming more and more common, with an incidence of about 1∶1 800. In the past decades, with the increase of cesarean section in China, the incidence of CSP has also risen, and especially after the implementation of the two-child policy in China, the harm of CSP to women has been gradually exposed. CSP is a kind of iatrogenic disease, which may cause serious complications during and after the operation, such as uncontrollable massive bleeding, uterine rupture, peripheral organ damage and even hysterectomy, which seriously threaten the reproductive health and even life of patients. Therefore, early diagnosis and treatment are essential for women. At present, there are different opinions on the pathogenesis of CSP, there are no normalized standards and guidelines and good evidence-based medical evidence at home and abroad for the selection of CSP treatment schemes, and there is a lack of randomized controlled studies with large sample size. Therefore, this article will review the etiology and treatment progress of CSP, in order to provide some reference for the selection of CSP treatment.

Abstract:Objective:　To investigate the prenatal diagnosis, clinical features and perinatal outcomes of placenta accreta spectrum (PAS) in different positions of the placenta. Methods:　All pregnant women who delivered at Ｔhe First Affiliated Hospital of Chongqing Medical University from January 2012 to December 2021 and were finally diagnosed with PAS were included. They were divided into three groups depending on the placenta location (anterior, posterior, lateral/uterine fundus). Prenatal diagnosis rate, clinical features and perinatal outcomes among the three groups were compared. Results:　A total of 2 070 pregnant women were included. In terms of basic characteristics, gravidity, parity, placenta previa rate, cesarean section times≥2 and previous history of placenta previa was significantly higher in the anterior placenta group (P<0.05). The placental accreta rate, multiple pregnancy, in vitro fertilization, vaginal delivery rate and delivery gestational age in the posterior group were higher than those in the anterior placenta group (P<0.05). In terms of grade of PAS and prenatal diagnosis rate, the incidence of placental increta and percreta in anterior wall was significantly higher than that in posterior wall, and the overall prenatal diagnosis rate of PAS was significantly higher than the other two groups (P<0.05) ; further comparison showed that the prenatal diagnosis rate of placental accreta in anterior wall was significantly higher than the other two groups (P<0.05) , and the diagnosis rate of placental increta in anterior wall was also higher than posterior wall (P<0.05) , and there was no statistically significant difference among the three groups in comparison of placenta percreta. Compared with the preoperative procedure, the abdominal aortic balloon, uterine packing, uterine binding, hysterectomy, and postoperative uterine artery embolization were higher in anterior placenta group (P<0.05). In terms of perinatal outcomes, 24 hours blood loss, transfusion of blood products, other organ damage, transfer to intensive care unit (ICU) and postoperative hospital stay were significantly higher in the anterior placenta group (P<0.05). The mean birth weight of neonates in the posterior placenta group was higher than that in the anterior placenta group (P<0.05). Conclusion:　The prenatal diagnosis rate of PAS in non-anterior placenta is low, but the rate of severe placenta accreta is higher in anterior placenta, and perinatal outcomes is much worse in anterior placenta. On the one hand, it is necessary to be more vigilant about the occurrence of PAS in posterior placenta, and if necessary, further diagnosis can be made by magnetic resonance imaging (MRI). On the other hand, active multidisciplinary management of pregnant women with prenatal diagnosis of PAS is necessary to improve the perinatal outcomes of these women.

Abstract:Objective:　To explore the influencing factors of adverse pregnancy outcomes in preeclampsia (PE) and build a risk prediction model. Methods:　The retrospective selection of PE patients admitted to the Ninth Affiliated Hospital of Suzhou University and the Affiliated Hospital of Nantong University from June 2018 to December 2020 as the modeling set (model development). According to whether the patients had adverse pregnancy outcomes within 48 hours of admission, they were divided into adverse group and nonadverse group. Single factor screening was performed for each index of the two groups. Multivariate logistic regression analysis was performed to analyze the influencing factors of adverse pregnancy outcomes in PE. Based on the filtered results, R language was used to build a risk prediction nomogram model. Receiver operating characteristic curve analysis and goodness-of-fit bias tests were used to evaluate model performance. Bootstrap method (self-sampling method) was used to verify and make calibration chart. A decision curve was used to evaluate the clinical benefit rate of the model. The PE patients admitted to Suzhou Ninth Hospital affiliated to Suzhou University from January 2021 to March 2022 were taken as the validation set. Results:　A total of 381 PE patients were included as the modeling set. Among them, 126 cases had adverse pregnancy outcomes, and 255 cases had no adverse pregnancy outcomes. A total of 102 PE patients were included as the validation set, among which, 34 had adverse pregnancy outcomes, and 68 had no adverse pregnancy outcomes. Logistic regression analysis showed: that the smaller the gestational age at admission (OR=2.672, 95%CI=1.495-5.153) , the more the number of clinical symptoms (OR=2.643, 95%CI=1.394-4.917) , and the higher the 24-hour proteinuria (OR=3.662, 95%CI=1.982-7.604) , lower platelet count (OR=2.396, 95%CI=1.307-4.653) , higher D-dimer (OR=2.929, 95%CI=1.728-5.843) , higher miR-21 expression levels (OR=4.302, 95%CI=2.426-9.185) were all influencing factors of adverse pregnancy outcomes in PE patients (P<0.05). Based on the above six factors, a risk prediction nomogram model was constructed. The area under the curve (AUC) of the model was 0.912 (95%CI=0.864-0.956) , the optimal cutoff value (the threshold probability) was 0.32, and the sensitivity and specificity at this time were 0.889 and 0.845, respectively; goodness-of-fit bias test ( χ²=4.214, P=0.837) ; the mean absolute error of the bias calibration curve was 0.013. The AUC of the validation set was 0.904 (95%CI=0.842-0.936) ; the sensitivity and specificity were 0.874 and 0.823, respectively; goodness-of-fit bias test (χ²=3.720, P=0.729) ; The mean absolute error of the bias calibration curve was 0.021. When the threshold probability value in the decision curve was set to 32.0%, clinical benefit rates for the modeling set and validation set were 69% and 76%, respectively. Conclusion:　Adverse pregnancy outcomes in PE patients are related to gestational age at admission, number of clinical symptoms, 24-h proteinuria, platelet count, D-dimer, and miR-21 expression. Risk prediction nomogram model constructed in this way has high prediction performance.

Abstract:Objective:　To explore the best placement time and effect evaluation of dinoprostone suppository for full-term pregnancy induction with different Bishop’s cervical scores. Methods:　Full-term pregnant women were divided into ≤3 groups, 4 groups and 5 groups according to Bishop’s cervical score. According to the placement time of dinoprostone suppository, each score group was divided into morning group (08:00-12:59) , afternoon group (13:00-17:59) and evening group (18:00-22:59) , and the effective rates of cervical ripening, stages of labor and pregnancy outcomes of all groups were retrospectively analyzed. Results:　A total of 1 139 pregnant women were enrolled, and the effective rate of cervical ripening was 93.59%. The effective rates of cervical ripening were 95.75%, 92.93% and 90.12% in each group with cervical score ≤3, 4 and 5 points before induction of labor (P<0.05). In the effective group, the incidence of amniotic fluid fecal contamination was 11.07%, fetal distress was 1.13%, and postpartum hemorrhage was 2.16%. Among the vaginal delivery women, when the Bishop score of cervix was less than or equal to 3, the primipara’s time from delivery to vaginal delivery was the shortest (4.82 h, P=0.005). The time from parturient to vaginal delivery was also the shortest (4.01 h, P=0.044). There was no significant difference in other indexes between groups. Conclusion:　Dinoprostolone suppository is safe and effective for induction of labor in full-term pregnancy. For pregnant women with cervical score≤3, dinoprostone suppository can be placed at night to induce labor. For those with cervical score > 3, it can be placed at a time when medical staff are energetic, convenient to operate and can observe closely.

Abstract:Objective:　To explore the optimal gestational weight gain (GWG) of twin pregnant women with different pre-pregnancy body mass index (BMI) through the range of uncomplicated twin pregnant women. Methods:　We divided pregnant women with twin pregnancies who delivered in Chongqing Maternal and Child Health Care Hospital into excellent outcome group and poor outcome group. Then, according to the pre-pregnant BMI, they were classified as underweight (BMI<18.5 kg/m²) , normal (18.5≤BMI<24.0 kg/m²) , overweight (24.0≤BMI<28.0 kg/m²) , and obese (BMI≥28.0 kg/m²). We used two methods to determine the optimal range of GWG. The first was a statistics-based approach: calculating the interquartile range of GWG for different BMIs in the excellent outcome group. The second method was the outcome-based method. To verify the rationality of optimal weekly GWG, we calculated the GWG rate (GWGR, total gestational weight gain/gestational weeks) and compared the incidence of maternal complications within and outside the optimal GWGR. Results:　The optimal GWG calculated in this study was lower than the GWG recommended by the Institute of Medicine (IOM). Except for the obese group, the overall incidence in the other three BMI groups within the optimal GWG was lower than that outside the optimal GWG. Insufficient GWGR increased the risk of gestational diabetes, premature rupture of membranes, preterm birth, and fetal growth restriction. Excessive GWGR increases the risk of gestational hypertension and preeclampsia. Conclusion:　Due to the limited sample size, except for the obese group, we provide preliminary recommendations for the optimal GWG in double chorionic twin pregnancies in China (16.0-21.0 kg for underweight, 14.5-21.0 kg for normal, and 13.0-20.0 kg for overweight).

Abstract:Objective:　To analyze the therapeutic effect and influencing factors of single dose methorexate (MTX) on tubal pregnancy patients with low and medium level β-hCG, and to provide some basis for clinical selection of reasonable treatment plans. Methods:　A retrospective study was carried out in 214 cases of tubal pregnancy with serum β-hCG lower than 1 500 IU/L using single dose MTX treatment and 80 cases of serum β-hCG 1 000-1 500 IU/L undergoing operation during the same period in our department from January to December 2020. According to the level of serum β-hCG before single dose MTX initial treatment, they were divided into three subgroups: group A (β -hCG<500 IU/L) ; group B (500 IU/L≤β-hCG<1 000 IU/L) ; group C (1 000 IU/L≤β-hCG<1 500 IU/L) , comparing the clinical efficacy and analyzing the factors of influencing the therapeutic effect. Results:　①There were no significant differences in mass size, pelvic effusion depth and hospital day among the three groups (P >0.05). Patients in group C had the highest hospitalization cost and transfer rate of surgery, and the lowest success rate of initial treatment (P<0.05) , but no statistically significant differences in hospitalization cost, transfer rate of surgery and success rate between group A and group B (P >0.05). There were no significant differences in the incidence of adverse reactions and persistent ectopic pregnancy among the three groups after single dose MTX treatment (P >0.05). The time from the first time to normal blood β-hCG in the three groups was statistically significant different (P<0.05) , with the shortest in group A and the longest in group C. ②In patients with serum β-hCG in the range of 1 000-1 500 IU/L, the mass size and pelvic ef-fusion depth were significant different between surgical treatment group and single dose MTX treatment group (P<0.05) , the length of hospital stay and the time for serum β-hCG to return to normal were shorter in the surgical treatment group than in the single dose MTX treatment group (P<0.05). ③For single dose MTX treatment patients, there were no significant differences in age and depth of pelvic effusion between successful group and failed group (P >0.05) , but there were significant differences in β-hCG level and mass size between two groups (P<0.05). ④In multivariate logistic regression analysis, 1 000 IU/L≤serum β-hCG<1 500 IU/L (OR=3.714, 95%CI=1.439-9.583) , and mass>3.5 cm (OR=3.022, 95%CI=1.298-7.037) was a risk factor for failure of single dose MTX therapy. Conclusion:　Patients with β-hCG≥1 000 IU/L have a higher failure rate of single-dose MTX treatment, and serum β-hCG≥1 000 IU/L and mass>3.5 cm are independent risk factors for the success rate of single dose MTX treatment. Surgical treatment seems to be more cost-effective for patients with β-hCG≥1 000 IU/L.

Abstract:Objective:　To observe the effects of a series of interventions to protect female fertility after surgical treatment of missed abortion in early pregnancy and the benefits in this population. Methods:　A total of 293 cases of missed abortion in early pregnancy were treated with standardized perioperative treatment and post-abortion care (PAC) services the complications such as bleeding and uterine perforation were observed, and the postoperative recovery, rebirth and unintended pregnancy were followed up. Results:　By standardized perioperative operation, the incidence of intraoperative complications was very low, and the clinical effect was positive. Among those having willness of fertility desire, 20.22% of them had the fertility intention to have a second pregnancy within 6 months after operation, and 46.45% had a second pregnancy within 1 year after operation. With the high quality PAC service in perioperative period, the contraceptive awareness of postoperative patients was significantly improved, and the unintended pregnancy rate was 1.82% in patients without family planning within one year. Conclusion:　The standardized operation and high quality PAC service in perioperative period can reduce the incidence of intraoperative complications, improve the recurrence rate of missed abortion in early pregnancy, reduce unintended pregnancy, and protect female fertility.

Abstract:As a common reproductive endocrine disease, premature ovarian insufficiency (POI) endangers women’s reproductive health and quality of life. Excessive apoptosis of ovarian granulosa cells has been confirmed to affect the development of follicles, which may be the pathogenesis of POI. It has been found that apoptosis of granulosa cells is related to PI3K/Akt/NF-κB signal pathway and the expression of apoptotic protein. Kidney-tonifying prescriptions can inhibit granulosa cell apoptosis, improve ovarian function, and regulate the expression of signal molecules related to PI3K/Akt/NF-κB signaling pathway. Therefore, combined with relevant literature reports, it is speculated that kidney-tonifying prescriptions may inhibit ovarian granulosa cell apoptosis by regulating PI3K/Akt/NF-κB signaling pathway to provide ideas and methods for basic research and clinical diagnosis and treatment of POI.

Abstract:Even though the infection of hepatitis B virus (HBV) has been reduced by the vaccination and the improvement of human health awareness, and the gradual development of antiviral drugs. So far, the elimination of HBV is still a serious problem. Hence, the accurate detection rate of HBV is extremely important. The traditional serum makers HBV DNA and hepatitis B surface antigen (HBsAg) have certain limitations in assessing the anti-HBV efficacy and accurately reflecting the transcriptional activity of covalently closed circular DNA (cccDNA). In order to solve this situation, novel HBV serum markers have been developed, such as HBV surface antigen, HBV RNA, HBV core related antigen, and HBV large surface protein. Based on the different reference values of different markers in disease diagnosis, this article briefly summarizes the clinical applications and limitations of these markers, which aims to provide references for the efficient and accurate detection of HBV and clinical prognosis.

Abstract:Chronic spontaneous urticaria (CSU) is a common allergic skin disease in clinical practice. Its pathogenesis is complex and has not been fully elucidated. According to the popular theory of helper T lymphocyte 1 (Th1) /Th2 cytokine imbalance in recent years, Th2 cytokines can directly or indirectly induce allergic diseases, and their abnormal secretion is closely related to the occurrence, development, and prognosis of CSU. In addition, in recent years, Th17 cytokines have also attracted the attention of researchers, and more and more evidence has shown that it plays an important role in CSU. The drug treatment for related cytokines has also made unprecedented progress. Therefore, this paper reviews the roles of Th2 and Th17-related cytokines in the occurrence and development of CSU, and provides references for subsequent research and treatment.

Abstract:Tuberculosis (TB) is one of the main causes of infectious diseases-related death in the whole world, which spreads worldwide and can invade widely all organs of the body, which poses a great threat to human health. Its occurrence and development are affected by many factors. Besides traditional environmental factors, genetic polymorphism has been paid more and more attention. Studies with interferon-γ (IFNG) , P2X7, vitamin D receptor (VDR) and other gene polymorphisms have been found to be significantly associated with the susceptibility of tuberculosis, and related research is bound to bring new ideas for tuberculosis prevention and treatment. In this paper, we systematically summarizes the genes related to the genetic susceptibility of tuberculosis, providing reference for tuberculosis prevention in the future.

Abstract:The liver is an important metabolism and detoxification organ of the human body. When affected by various pathogenic factors, the normal physiological and biochemical functions of the liver are affected, leading to liver diseases. Leukocyte cell-derived chemotaxin-2 (LECT2) is a basic protein secreted mainly by liver cells, which has many important functions in various systems of the human body, such as controlling and regulating the immune system, changing glucose metabolism, promoting bone growth, controlling cell cycle and division, etc. The clinical significance of changes in LECT2 levels in different disease states is different. In patients with different types of liver diseases, the level of LECT2 in serum and liver tissue is closely related to the decline of liver function and pathological staging. A large number of animal studies and in vitro experiments have shown that the abnormal expression of LECT2 leads to metabolic disorders, liver inflammation, fibrosis and tumors. This article reviews the relevant domestic and foreign literature in recent years, and reviews the molecular concept of LECT2 and its relationship with the occurrence and development of liver diseases, invasion and metastasis, etc., to explore whether LECT2 can be used as a potential target for the treatment of different liver diseases.

Abstract:Objective:　To investigate the protective effect of dexmedetomidine (DEX) on bleomycin (BLM) -induced pulmonary fibrosis in mice and its effect on toll-like receptor 4/myeloid differentiation factor88 (TLR4/MyD88) signaling pathway. Methods:　Experimental mouse pulmonary fibrosis was induced by injection of BLM. The mice were grouped into: saline (Sham) group, BLM group, BLM+DEX group, BLM+PFD group, and BLM+DEX+LPS group. The pathological changes of lung tissue were analyzed by hematoxylin and eosin (HE) and Masson staining; the expression of fibronectin (Fn) , α-smooth muscle actin (α-SMA) and type Ⅰ collagen (collagen Ⅰ) was measured by immunohistochemistry; the apoptosis in lung tissue was measured by TdT mediated dUTP nick end labeling (TUNEL) ; the total cell number and protein content in bronchoalveolar lavage fluid (BALF) were measured; and the TLR4/MyD88 signaling pathway and apoptosis-related protein levels in lung tissue were detected by Western blot. Results:　Compared with the Sham group, the alveolitis score [(2.56±0.24) points vs. (0.15±0.02) points] and Ashcroft score [(5.68±0.52) points vs. (0.09±0.01) points] in lung tissue after BLM stimulation increased significantly, the expression of Fn [(63.63±5.48) % vs. (25.12±2.16) %], α-SMA [(58.63 ± 5.03) % vs. (17.56±1.25) %] and collagenⅠ [(55.32 ± 5.16) % vs. (12.03±1.20) %] increased (P<0.05) , and the degrees of lung inflammation and fibrosis increased. Meantime, the rate of TUNEL positive cells increased, the level of bcl-2 associated X protein (Bax) protein in the cells increased, and the level of B-cell lymphoma-2 (Bcl-2) protein decreased (P<0.05) ; the total cell number [(3.54±0.06) ×10⁵/mL vs. (0.98±0.07) ×10⁵/mL] and protein content [(2.85±0.20) mg/mL vs. (0.29±0.03) mg/mL] increased in BALF (P<0.05) ; the protein levels of TLR4 and MyD88 in lung tissue were increased (P<0.05). DEX treatment attenuated BLM-induced pulmonary fibrosis and inflammation in mice, decreased the rate of TUNEL-positive cells, and reversed the expression of Fn, α-SMA, collagen I, Bax and Bcl-2 (P<0.05) ; meanwhile, DEX also decreased the total cell number and protein content in BLM-induced mouse BALF (P<0.05) ; in addition, DEX reduced TLR4 and MyD88 protein levels in BLM-induced mouse lung tissue (P<0.05). Pirfenidone (PFD) and DEX had similar effects; lipase (LPS) was able to partially reverse the protective effect of DEX on BLM-induced pulmonary fibrosis in mice (P<0.05). Conclusion:　DEX may improve BLM-induced pulmonary fibrosis in mice by inhibiting TLR4/MyD88 signaling pathway.

Abstract:Objective:　To investigate chemoattractant receptor homologous molecule expressed on Th2 cells (CRTh2) , cysteinyl leukotriene 1 receptor (CysLT1R) and histamine 1 receptor (H1R) expression and clinical significance in peripheral blood CD3⁺CD56⁺ natural killer T cells (NKT) of patients with bronchial asthma (BA). Methods:　The peripheral blood of BA patients (BA group, n=40) and healthy control group (HC group, n=38) in The First Affiliated Hospital of Jinzhou Medical University from September 2020 to September 2021 were collected, and flow cytometry was used to detect the BA group and HC group expression of CRTh2, CysLT1R and H1R on CD3⁺CD56⁺ labeled NKT cells in peripheral blood. At the same time, its correlation with serum total immunoglobulin E (TIgE) , fractional exhaled nitric oxide (FeNO) and lung function forced expiratory volume in the first second/forced vital capacity% (FEV1/FVC%) were analyzed. Results:　The percentage of NKT cells in the peripheral blood of the BA group[22.50 (15.78, 29.20)] was lower than that in the HC group[27.90 (21.50, 32.45)] (P=0.024). And in the further comparison, the percentage of CD3⁺ lymphocytes in the BA group[70.05 (63.20, 78.45)] was lower than that in the HC group[73.70 (69.88, 79.38)] (P=0.035). The percentage of CysLT1R in the BA group[0.08 (0.05, 0.17)] was lower than that in the HC group[0.16 (0.10, 0.34)] (P=0.004). The percentages of CRTH2 and H1R in the BA group[1.12 (0.53, 1.88) ; 5.21 (1.41, 10.10)] were not significantly different from those in the HC group[1.17 (0.60, 4.25) ; 4.61 (1.42, 8.53)] (P=0.234; P=0.697). Additionally, for the further comparison of the mean fluorescence intensity (MFI) of CRTh2 and H1R, BA group[925.52 (623.50, 1 279.25)] CRTh2 MFI was lower than HC group[1 345.50 (891.00, 1 977.75)] (P=0.002) ; there was no significant difference in H1R MFI between BA group[769 (657.50, 975.00)] H1R MFI and HC group[835.00 (560.00, 959.25)] (P=0.834). CD3⁺CD56⁺NKT cells had no significant correlation with serum TIgE and FeNO (r=-0.052; r=0.014) , but was positively correlated with the level of FEV1/FVC% (r=0.402, P=0.01). CRTH2 (r=0.166, r=-0.040) , CysLT1R (r=0.114, r=-0.150) and H1R (r=0.103, r=-0.096) had no significant correlation with TIgE and FeNO. Conclusion:　CD3⁺CD56⁺NKT cells may play an important role in the pathogenesis of bronchial asthma, H1R may not be expressed on CD3⁺CD56⁺NKT cells, and the decreased expression of CRTh2 and CysLT1R on CD3⁺CD56⁺NKT cells in BA patients may provide a basis for accurate clinical diagnosis and treatment.

Abstract:Objective:　To observe the effects of acupuncture plus medication therapy on behavior, intestinal flora, and the expression of 5-hydroxytryptamine (5-HT) and 5-hydroxytryptophan (5-HTP) in depressed rats, and to explore the possible mechanism of acupuncture plus medication in the treatment of depression. Methods:　Thirty-five male SD rats were randomly divided into a blank group, a model group, an electroacupuncture (EA) group, a fluoxetine group, and an acupuncture plus medication group, with 7 rats in each group. The depressed rat model was prepared by exposing to chronic unpredictable mild stress (CUMS). In the EA group and the acupuncture plus medication group, the rats were intervened by EA at "Yaoyangguan" , bilateral "Tianshu" , "Zusanli" , and "Changshu" , 30 minutes each time, once a day for 21 days. In the fluoxetine group and the acupuncture plus medication group, the rats received intragastric administration with 0.2% fluoxetine at 10 mg/kg, once a day for 21 days. The sucrose preference test (SPT) , open field test (OFT) , and forced swimming test (FST) were performed to analyze the behavioral changes of rats. The diversity of intestinal flora was detected by 16S rDNA high-throughput sequencing. The levels of 5-HT in hippocampus, colon, and serum, and 5-HTP in colon and serum were detected by enzyme-linked immunosorbent assay (ELISA). Results:　Compared with the blank group, in the model group, the sugar water consumption of SPT and the total distance of OPT were significantly decreased, the immobility time of FST was significantly increased, the levels of 5-HT in hippocampus, 5-HT and 5-HTP in colon tissue and serum were significantly decreased (P<0.01) , and the species and relative abundance of intestinal beneficial flora were decreased. Compared with the model group, in each intervention groups, the sugar water consumption of SPT and the total distance of OPT were significantly increased, the immobility time of FST was significantly decreased, the levels of 5-HT in hippocampus, 5-HT and 5-HTP in colon tissue and serum were increased (P<0.01, P<0.05) , and the species and relative abundance of intestinal beneficial flora were increased. Compared with the fluoxetine group, in the acupuncture plus medication, the immobility time of FST was decreased, the levels of 5-HT in hippocampus and serum were increased (P<0.05) , and the increasing trend of beneficial flora and the decreasing trend of harmful flora was more obvious. Conclusion:　Acupuncture plus fluoxetine therapy could significantly alleviate the depression-like behavior in CUMS rats. And its mechanism may be related to the increasing the species and relative abundance of intestinal beneficial flora and up-regulating the expression of brain-gut axis 5-HT, 5-HTP and other related molecules.

Abstract:Objective:　To investigate the effect of palatal lift prosthesis (PLP) on the curative effect and nasal flow of patients with dysarthria. Methods:　From April 2020 to January 2021, 18 patients (15 males and 3 females) with dysarthria and severe velopharyngeal insufficiency (VPI) who underwent language training in the Department of Rehabilitation Medicine, Binzhou Medical University Hospital were included in the study, aged from 16 to 59, with an average age of 38.0 years old. The PLP group received PLP and rehabil-itation training (excluding training to overcome nasalization) , and the pure training group only received rehabilitation training, with a treatment course of 20 days. The two groups of patients underwent velopharyngeal lateral X-rays (photostatic and phonation/i/audiovisual each) measurement, and nasal flow tester to test the nasal flow, to determine the longest vocalization time, the speed of vocal rotation and the speech clarity. Results:　In patients with dysarthria and severe VPI, the soft palate movement angle decreased, and the relative VPI rate increased. In the PLP group, the angle of movement of the soft palate was significantly increased compared to before treatment. The shortest distance between the soft palate and the posterior pharyngeal wall and the relative VPI rate were significantly reduced compared with before, the nasal flow was significantly reduced, the longest vocalization time was significantly prolonged, and the pronunciation was alternated. Movement speed was significantly increased, speech clarity was significantly improved, and the above indicators improved more significantly after wearing PLP and undergoing the training. Conclusion:　PLP is an effective method to improve nasalization in patients with dysarthria and severe VPI. It can also improve the patient's longest vocalization time, vocal rotation speed and speech clarity.

Abstract:Objective:　To explore the efficacy and safety of the third-line or above therapy of inetetamab combined with pyrotinib in patients with advanced Her2 positive breast cancer. Methods:　Clinical data of 10 patients with advanced Her2 positive breast cancer treated with inetetamab combined with pyrotinib after the failure of multiline therapy were collected to analyze the short-term efficacy, adverse reactions, and the survival. Results:　The follow-up went until April 1, 2021. The objective response rate was 90% (9/10) , and the median progression-free survival time was 5.87 months. The efficacy of 10 patients with advanced Her2 positive breast cancer was as follows: 0 case of CR; 9 cases of PR, of which 1 PR patient suffered interruption for economic reasons and was remained stable. The progression-free survival time of the other PR patient was 5 months, and then the patient died of the progress of pulmonary metastasis, pleural effusion, and atelectasis, despite emergency rescue efforts. After 9 courses of treatment, 1 PR patient changed the therapy due to "the progression of pulmonary metastasis" , and the condition was still under evaluation. The remaining 6 patients were still in follow-up. One SD patient was treated with advanced fifth-line therapy, and the progression-free survival of the SD patient was 1.5 months. The SD patient died of the progression of pulmonary metastasis, despite emergency rescue efforts. The main adverse reactions during treatment were fatigue, stomach distension, and diarrhea. Of these, 70% (7/10) of patients had grade 2-3 fatigue and stomach distention, and 90% (9/10) of patients had grade 1-2 diarrhea. Most patients had mild bone marrow suppression in the combination with chemotherapy. Conclusion:　The treatment regimen of inetetamab combined with pyrotinib (China double target) in patients with advanced Her2 positive breast cancer after the failure of multi-line therapy has significant short-term efficacy and good safety, which is worthy of further large sample follow-up observation and comparative study.

Abstract:Objective:　To study the expression of ITGA2 (integrin alpha-2) in pancreatic adenocarcinoma, the relationship between expression and prognosis, the relationship between expression and clinicopathological characteristics, and to further predict the biological function of ITGA2. Methods:　The GEPIA online tool was used to analyze the expression difference of ITGA2 gene in pancreatic adenocarcinoma tissues and normal tissues in The Cancer Genome Atlas (TCGA) database, and the relationship between the expression level and survival prognosis was analyzed retrospectively. The LinkedOmics database was used to screen the list of co-expressed genes of ITGA2 in pancreatic adenocarcinoma, and the biological functions were analyzed in the WebGestalt database. The clinical information and ITGA2 expression data of pancreatic adenocarcinoma patients was downloaded, the relationship between ITGA2 expression and clinicopathological characteristics was analyzed, and the risk factors that would affect survival and prognosis of pancreatic adenocarcinoma was studied. Results:　ITGA2 was significantly highly expressed in pancreatic adenocarcinoma tissues (P<0.05). Compared with patients with low expression, the overall survival of pancreatic adenocarcinoma patients with high ITGA2 expression (log-rank P=0.002) and disease-free survival (log-rank P=0.004) significantly reduced. Using LinkedOmics, 278 genes co-expressed with ITGA2 were identified. Gene Ontology (GO) analysis showed that these genes were mainly involved in biological processes such as cell adhesion, intercellular junction composition, and cytoskeleton formation; Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed significant enrichment in focal adhesions, adhesion junctions, tight junctions, regulation of actin cytoskeleton, tumor proteoglycans and other pathways. The expression level of ITGA2 was significantly correlated with tumor stage (χ²=6.380, P=0.036) , tumor size or invasion range (χ²=5.214, P=0.022) , and degree of tumor differentiation (χ²=11.998, P=0.002). Cox regression analysis showed that the expression level of ITGA2 was an independent risk factor affecting the prognosis of patients with pancreatic cancer (HR=1.888, 95%CI=1.021-3.490, P=0.043). Conclusion:　ITGA2 gene is closely related to the occurrence and development of pancreatic adenocarcinoma, which can be used as a clinical marker to determine the prognosis of pancreatic adenocarcinoma and has the potential to become a tumor treatment target.

Abstract:Objective:　To explore the core genes and pathways of esophageal adenocarcinoma (EAC). Methods:　The differentially expressed genes between EAC tissue and normal esophageal tissue were analyzed with GEO database. A variety of online analysis software were used for functional enrichment, pathway analysis, construction of protein-protein interaction network, and selection of core genes. Combined with TCGA and Oncomine database, the core genes were verified, the ROC curves were drawn and the area under the curve (AUC) was calculated. Results:　A total of 141 core genes were obtained from 4 GEO datasets, which were mainly enriched in the extracellular matrix, mainly in glycolysis/gluconeogenesis pathways, and tyrosine, histidine, phenylalanine and β-alanine metabolic pathways. COL1A2, TIMP1 and MMP1 were screened out in TCGA and Oncomine databases. The AUC of COL1A2 was 0.707-0.954, that of TIMP1 was 0.795-0.984, and that of MMP1 is 0.896-1.000. Conclusion:　Screening out core genes and pathways related to EAC by bioinformatics is helpful for early molecular diagnosis and gene targeted therapy of EAC.

Abstract:Objective:　To explore the mechanisms of colorectal cancer (CRC) metastasis and find the potential biomarkers associated with metastasis and prognosis by analyzing the gene profiles with bioinformatics analysis. Methods:　The gene profiles of GSE41568, GSE68468 were selected from the GEO database; R software with the limma package was used to analyze the data and screen the differentially expressed genes between primary tumors and metastatic tumors, and we got the common differentially expressed genes. ClusterProfiler package was used for the biological function enrichment analysis and visualization; STRING database and Cytoscape software were used to construct protein-protein interaction (PPI) network and identify the key modules; TCGA database was applied for the expression analysis and survival analysis of common differentially expressed genes. Results:　We identified 108 common differentially expressed genes between primary tumors and metastatic tumors. Enrichment analysis indicated that the genes were enriched in complement and coagulation cascades pathways and biological processes, et al. We also found 3 key modules by PPI network analysis. The analysis of common differentially expressed genes based on TCGA data showed that there were significant differences in the expression of CLCA1, COLEC11, FCGBP, PDZD2, SERPINA1, and SPINK4 between the stage Ⅰ-Ⅱ and Ⅲ-Ⅳ of CRC (P<0.05) , with significant correlation with the prognosis of CRC (P<0.05). Conclusion:　With bioinformatics analysis, a total of 108 common differentially expressed genes, 3 key modules and 6 genes associated with prognosis have been screened out, thereby providing the theoretical support for research on mechanisms of metastasis, prognosis prediction and targeted therapies of CRC.

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