Effects of Zishen Yutai Pills on in vitro Fertilization-Embryo Transfer Outcomes in Patients with Diminished Ovarian Reserve: A Prospective, Open-Labeled, Randomized and Controlled Study / 中国结合医学杂志

OBJECTIVE@#To explore the effects of Zishen Yutai Pills (ZYPs) on the quality of oocytes and embryos, as well as pregnancy outcomes in patients with diminished ovarian reserve (DOR) receiving in vitro fertilization-embryo transfer (IVF-ET). The possible mechanisms, involving the regulation of bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9), were also investigated.@*METHODS@#A total of 120 patients with DOR who underwent their IVF-ET cycle were randomly allocated to 2 groups in a 1:1 ratio. The patients in the treatment group (60 cases) received ZYPs from the mid-luteal phase of the former menstrual cycle by using gonadotropin-releasing hormone (GnRH) antagonist protocol. The patients in the control group (60 cases) received the same protocol but without ZYPs. The primary outcomes were the number of oocytes retrieved and high-quality embryos. Secondary outcomes included other oocyte or embryo indices as well as pregnancy outcomes. Adverse events were assessed by comparison of the incidence of ectopic pregnancy, pregnancy complications, pregnancy loss, and preterm birth. Contents of BMP15 and GDF9 in the follicle fluids (FF) were also quantified with enzyme-linked immunosorbent assay.@*RESULTS@#Compared with the control group, the numbers of oocytes retrieved and high-quality embryos were significantly increased in the ZYPs group (both P<0.05). After treatment with ZYPs, a significant regulation of serum sex hormones was observed, including progesterone and estradiol. Both hormones were up-regulated compared with the control group (P=0.014 and 0.008), respectively. No significant differences were observed with regard to pregnancy outcomes including implantation rates, biochemical pregnancy rates, clinical pregnancy rates, live birth rates, and pregnancy loss rates (all P>0.05). The administration of ZYPs did not increase the incidence of adverse events. The expressions of BMP15 and GDF9 in the ZYPs group were significantly up-regulated compared with the control group (both P<0.05).@*CONCLUSIONS@#ZYPs exhibited beneficial effects in DOR patients undergoing IVF-ET, resulting in increments of oocytes and embryos, and up-regulation of BMP15 and GDF9 expressions in the FF. However, the effects of ZYPs on pregnancy outcomes should be assessed in clinical trials with larger sample sizes (Trial reqistration No. ChiCTR2100048441).

Mitochondrial Function Reveals Connotation of "Seven-Seven" Theory of Huangdi's Internal Classic and Mechanism of Herbal Intervention for Elderly Women Undergoing IVF-ET / 中国实验方剂学杂志

ObjectiveTo study the changes of mitochondrial function of ovarian granulosa cells in women of different ages and the effect of Erzhi-Tiangui prescription on in vitro fertilization-embryo transfer （IVF-ET） outcomes for elderly women， so as to verify the connotation of the "Seven-Seven" theory in the Huangdi's Internal Classic （《黄帝内经》）. MethodA total of 150 infertility patients undergoing IVF-ET at the Reproductive and Genetic Center of Integrative Medicine， Affiliated Hospital of Shandong University of Traditional Chinese Medicine were recruited and assigned into "hree-Seven/Four-Seven （30 cases）， Five-Seven （60 cases）， and Six-Seven （60 cases） groups according to the "Seven-Seven" theory. The Five-Seven and Six-Seven groups were further assigned into control and Chinese medicine subgroups using the random number plus envelope method， and the Chinese medicine group was administrated with Erzhi Tiangui prescription from the start day of controlled ovulation stimulation cycle to the trigger day. The IVF outcome was observed， and Western blot was employed to determine the levels of mitofusin 1 （MFN1）， mitofusin 2 （MFN2）， and dynamin-related protein 1 （Drp1） in the ovarian granulosa cells. ResultCompared with the Three-Seven/Four-Seven group， the control subgroups of the Five-Seven and Six-Seven groups showed decreased retrieved oocytes， two pronuclear （2PN） embryos， available embryos， high-quality embryos， clinical pregnancy rate， and live birth rate （P<0.05）. Moreover， the control subgroup of the Six-Seven group showed decreased fresh embryo transfer rate（P<0.05）. Compared with the control subgroup of the Five-Seven group， that of the Six-Seven group showed reduced retrieved oocytes， 2PN embryos， available embryos， high-quality embryos， and clinical pregnancy rate （P<0.05）. The Chinese medicine subgroup had more retrieved oocytes， 2PN oocytes， and available embryos than the control subgroup in the Five-Seven groups （P<0.05）. The Chinese medicine subgroup had more retrieved oocytes， than the control subgroup in the Six-Seven groups （P<0.05）. The control subgroup of the Six-Seven group showed lower expression levels of Mfn1 and Mfn2 and higher level of Drp1 than the control subgroup of the Five-Seven group （P<0.05）， which indicated that the levels of Mfn1 and Mfn2 in ovarian granulosa cells were down-regulated while the expression of Drp1 was up-regulated with aging （P<0.05）. The Chinese medicine subgroup had higher Mfn2 level and lower Drp1 level than the control subgroup in the Five-Seven group （P<0.05）， and the Chinese medicine subgroup had higher Mfn1 and Mfn2 levels and lower Drp1 level than then control subgroup in the Six-Seven group （P<0.05）. ConclusionsThe prognosis of IVF in women after "Five-Seven" became worse with aging， and the mitochondria in ovarian granulosa cells showed decreased fusion ability and increased fission， which verified the connotation of the "Seven-Seven" theory from the mitochondrial function. Erzhi Tiangui prescription can regulate the mitochondrial function of ovarian granulosa cells in elderly women， up-regulate the expression levels of Mfn1 and Mfn2 to promote mitochondrial fusion， and down-regulate the expression of Drp1 to reduce mitochondrial fission， thus alleviating the ovarian hypofunction caused by aging， improve the development potential of oocytes， and improve the IVF outcomes of elderly women. However， this prescription has limited efficacy for the elderly women in the age range of "Six-Seven".

Prevention and Treatment of Age-related Ovarian Hypofunction with Traditional Chinese Medicine： A Review / 中国实验方剂学杂志

Age-related ovarian hypofunction includes a decrease in follicle quantity and quality as well as alterations in the ovarian microenvironment，the mechanisms of which are mainly related to mitochondrial dysfunction，free radical and antioxidant systems，telomere and telomerase alterations，and apoptosis，and is one of the major factors contributing to infertility in advanced maternal age （AMA）. Despite the tremendous progress in assisted reproductive technology in recent decades，few breakthroughs have been made in alleviating age-related ovarian hypofunction and improving reproductive outcomes for AMA. In recent years，there has been an increasing number of studies on the multi-level and multi-targeted mechanisms of traditional Chinese medicine （TCM） to improve age-related ovarian hypofunction by modulating mitochondrial homeostasis，alleviating oxidative stress，and inhibiting apoptosis，while more high-quality randomized controlled trials have demonstrated the clinical efficacy of TCM in assisted reproductive technology. Given this，this article presented a systematic review of recent research and randomized controlled trials on the mechanism of Chinese medicine active ingredients，single Chinese medicine， and Chinese medicine compounds in delaying age-related ovarian hypofunction，to clarify the current status and shortcomings of the research. This paper provides medication management of TCM for effectively alleviating age-related ovarian hypofunction and improving reproductive outcomes for AMA.

Research progress in prevention and treatment of repeated implantation failure by TCM compounds based on "Yu Pei Qi Sun" theory / 国际中医中药杂志

Women undergoing in vitro fertilization-embryo transfer (IVF-ET) may experience repeated implantation failure (RIF). Under the guidance of "Yu Pei Qi Sun" theory, Traditional Chinese Medicine (TCM) compounds can improve the quality of sperm and eggs of both husband and wife by anti-oxidative stress, improving mitochondrial function and reducing excessive apoptosis before IVF-ET to obtain high-quality embryos; TCM compounds can also promote angiogenesis, anti-oxidative stress, regulation of estrogen and progesterone receptor content, regulate immunity to improve female endometrial receptivity to facilitate embryo implantation; it can also invigorate the spleen and kidney after transplantation and caring for the fetus to help implantation, as well as alleviate the anxiety of patients during transplantation.

Clinical Efficacy and Mechanism of Erzhi Tiangui Prescription in Treatment of Patients with Repeated Implantation Failure of Kidney Deficiency Syndrome Based on sPD-1 and Th17/Treg Cytokines / 中国实验方剂学杂志

ObjectiveTo investigate the clinical efficacy and possible mechanism of Erzhi Tiangui prescription on repeated implantation failure （RIF） of kidney deficiency syndrome. MethodSeventy patients with RIF of kidney deficiency syndrome who underwent natural cycle frozen-thawed embryo transfer （FET） in the Reproductive and Genetic Center of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine were enrolled and randomly divided into a treatment group （35 cases） and a control group （35 cases）. Patients in the treatment group took oral Erzhi Tiangui prescription from the third day of each menstrual cycle two months before the FET cycle and continued to take it until the day of transplantation from the third day of the menstrual cycle in the month of transplantation. Those in the control group did not accept traditional Chinese medicine （TCM）. In addition，10 patients who successfully achieved clinical pregnancy after the first natural cycle FET were screened from the reproductive medical record bank of this hospital and assigned to the normal group. Peripheral blood samples of patients in the three groups on the day of embryo transfer were collected from the specimen bank of the Reproductive and Genetic Center. Serum soluble programmed death molecule-1 （sPD-1），soluble programmed death molecule-ligand 1 （sPD-L1），transforming growth factor-β （TGF-β），interleukin-17 （IL-17）， and interleukin-10 （IL-10） levels were measured by enzyme-linked immunosorbent assay （ELISA）. The changes in kidney deficiency syndrome scores， the final biochemical pregnancy rates， clinical pregnancy rates， and embryo implantation rates of the treatment group and the control group before and after treatment were observed. ResultCompared with the normal group，the model group showed increased serum levels of sPD-1 and IL-17（r=0.347，P<0.05），decreased levels of IL-10 and TGF-β （P<0.01），and non-significant change in sPD-L1 level. Serum sPD-1 was positively correlated with IL-17 （P<0.05） and negatively correlated with IL-10（r=-0.521，P<0.01） and TGF-β（r=-0.457，P<0.01） in RIF patients with kidney deficiency syndrome. After TCM treatment，compared with the control group， the treatment group showed improved TCM syndrome score （P<0.05） and increased clinical pregnancy rate and embryo transfer rate（P<0.05），but there was no statistically significant difference in the biochemical pregnancy rate between the two groups. ConclusionAbnormal expression of sPD-1 in patients with RIF of kidney deficiency syndrome breaks the balance of T helper 17 （Th17）/regulatory T cell （Treg），which is not conducive to embryo implantation and pregnancy maintenance. Erzhi Tiangui prescription，a TCM for tonifying the kidney，can significantly improve the symptoms of kidney deficiency in patients with RIF of kidney deficiency syndrome，reduce the concentrations of sPD-1 and IL-17 in the peripheral serum，increase the levels of TGF-β and IL-10，regulate the peripheral Th17/Treg immune balance，and increase the implantation rate and clinical pregnancy rate，which has a high clinical value.

Effect of Electro-acupuncture on Expression of IRS-1/PI3K/GLUT4 Pathway in Ovarian Granulosa Cells of Infertile Patients with Polycystic Ovary Syndrome-Insulin Resistance of Phlegm-Dampness Syndrome / 中国结合医学杂志

OBJECTIVE@#To evaluate the effect of electro-acupuncture (EA) in infertile patients with phlegm-dampness polycystic ovary syndrome-insulin resistance (PCOS-IR).@*METHODS@#Seventy-six PCOS-IR patients who underwnet in vitro fertilization and embryo transfer (IVF-ET) were equally assigned to two groups according to a random digital table: the EA group and the control group, with 38 cases in each group. Before undergoing IVF, the two groups were treated with EA or pseudo-acupuncture, respectively, for 3 menstrual cycles. The intervention was 25 min twice a week until the day of oocyte collection. The selected acupoints were Zhongwan (RN 12), Tianshu (ST 25), Daheng (SP 15), Daimai (GB 26), Qihai (CV 6), Guanyuan (CV 4), and bilateral points including Xuehai (SP 10), Fenglong (ST 40), Zusanli (ST 36), and Yinlingquan (SP 9). Evaluation of phlegm-dampness syndrome score and IR score were carried out before and after treatment. Additionally, the number of oocytes retrieved, transplantable embryo rate, high-quality embryo rate, clinical pregnancy rate and live birth rate were compared between the two groups. Real-time polymerase chain reaction analysis was used to monitor the mRNA expression of the insulin receptor substrate (IRS-1), phosphatidylinositiol 3-kinase (PI3K) and glucose transport factor 4 (GLUT4) in ovarian granulosa cells.@*RESULTS@#EA treatment reduced the phlegm-dampness syndrome score as well as the IR scores compared with the control group (P0.05). Moreover, the transplantable embryo rate [49.0% (284/580) vs. 41.9% (273/652)], high-quality embryo rate [36.6% (104/284) vs. 27.8% (76/273)], and live birth rate [50% (19/38) vs. 26.3% (10/38)] in the EA group were significantly higher than in the control group (P<0.05). Gene expression analyses revealed significantly elevated IRS-1, PI3K and GLUT4 mRNA in ovarian granulosa cells of the EA group compared with the control group (P<0.05).@*CONCLUSIONS@#EA may ameliorate the effects of phlegm-dampness syndrome and ovarian IR in PCOS-IR patients. Mechanistically, this effect might be through an upregulation of the IRS-1/PI3K/GLUT4 signaling pathway, which may result in improved oocyte quality and embryonic development potential. (Registration No. ChiCTR1800015453).

Efficacy and peripheral immunity analysis of allogeneic natural killer cells therapy in patients with hepatocellular carcinoma / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the safety and efficacy of allogeneic natural killer (NK) cells in the treatment of primary hepatocellular carcinoma (HCC), and to elucidate the mechanism of NK cells therapy.@*METHODS@#Twenty-one patients with primary HCC treated with allogeneic NK cells at the Fifth Medical Center of the PLA General Hospital were followed up for 1 year. Peripheral blood mononuclear cells (PBMCs) were isolated from patient-related donors and cultured in vitro for 15 days and infused to the patients in two consecutive days. Clinical data and laboratory data were collected and analyzed, including survival, clinical features, imaging changes, hematology, immunology, and biochemical indicators to evaluate the safety and efficacy of allogeneic NK cell therapy. The changes of peripheral blood lymphocyte subsets after treatment were also analyzed to explore the possible anti-tumor mechanisms.@*RESULTS@#(1) Of the 21 patients with primary HCC, 11 patients were treated once, 5 patients were treated twice, and 5 patients were treated 3 times. After allogeneic NK cells infusion, 10 patients had fever, 1 patient had slight hepatalgia and 1 patient had slight headache, no other adverse events occurred including acute and chronic graft-versus-host disease (GVHD). They resolved spontaneously within 8 hours without other treatment. (2) The total disease control rate was 76.2% during one-year follow-up. Among them, the patients with Barcelona clinic liver cancer (BCLC) stage A had a disease control rate of 100%, stable disease (SD) in 10 cases; BCLC stage B patients had a disease control rate of 60%, partial response (PR) in 1 case, and SD 2 in cases; BCLC stage C patients had a disease control rate of 50%, complete response (CR) in 1 case, and 2 cases of PR. (3) The frequencies of NK cells and CD8+ T cells in peripheral blood were significantly lower than that before at 24 hours after treatment, and the frequencies of CD4+ T cells and CD4/CD8 were significantly higher than the baseline.@*CONCLUSION@#Allogeneic NK cells have good safety and efficacy in the treatment of primary HCC. The anti-tumor effect of the allogeneic NK cells may play an important role in the activation of the patient's natural immune system and delay disease progression, suggesting that allogeneic NK cells combined with sorafenib may be a very effective treatment for advanced HCC, and further large-sample multicenter randomized controlled clinical trials are needed to validate this result.

Distribution and drug resistance of clinically isolated pathogenic bacteria at a tertiary care hospital in Haikou, China

Objective: To analyze the distribution and drug resistance of clinical isolated pathogens to provide reference for rational use of antimicrobial agents. Methods: We retrospectively analyzed the distribution and drug resistance data of clinical bacterial isolates from the Second Affiliated Hospital of Hainan Medical University from Jan 2018 to Dec 2018 and their clinical distribution and drug resistance were analyzed. Results: The results of comprehensive analysis of 7 897 non-repetitive bacteria showed that 5 044 strains (63.87%) were Gram-negative bacteria, 1 818 strains (23.02%) were Gram-positive bacteria, and 1 035 strains (13.11%) were fungi. Gram-negative bacteria mainly were Pseudomonas aeruginosa (15.44%), Escherichia coli (12.79%) and Acinetobacter baumannii (8.66%). Gram-positive bacteria mainly were Staphylococcus aureus (6.43%), Enterococcus faecium (4.89%) and Enterococcus faecalis (4.65%). The main fungi were Candida albicans (6.34%). Most of the collected and tested samples were urine (32.87%), followed by sputum (30.10%) and wound secretion (13.54%). In emergency department, intensive care unit and urology department, the detection rate of pathogens was most frequently found among three departments. Escherichia coli had higher resistance to ampicillin, tetracyclin and piperacillin, but were sensitive to imipenem and meropenem. Pseudomonas aeruginosa were sensitive to amikacin, tobramycin and gentamycin. Acinetobacter baumannii had higher resistance to cefotaxime, cefepime, and they were sensitive to minocycline. Among Staphylococcus aureus, a total of 123 strains of MRSA (24.21%) were more resistant to penicillin, azithromycin and erythromycin, but sensitive to vancomycin, linezolid and taicoplanin. Conclusions: The problem of drug resistance of clinical isolated pathogens was serious. The hospital should strengthen the dynamic monitoring of drug resistant bacteria. Antibiotics should be used rationally to reduce the spread of drug resistant strains and effective measures must be taken to prevent infections.

Effects of Electroacupuncture on Expression of PI3K/Akt/Foxo3a in Granulosa Cells from Women with Shen (Kidney) Deficiency Syndrome Undergoing in vitro Fertilization-Embryo Transfer / 中国结合医学杂志

OBJECTIVE@#To observe the effects of electroacupuncture (EA) on reproductive outcomes in women with Shen (Kidndy) deficiency syndrome after in vitro fertilization-embryo transfer (IVF-ET), and explore the underlying molecular mechanism.@*METHODS@#Sixty-six infertile patients with Shen deficiency syndrome undergoing IVF-ET were divided into EA or control groups according to a random table, 33 cases in each group. Before undergoing IVF, patients in the EA and control groups received EA therapy and placebo needle puncture, respectively, for 3 menstrual cycles. Shen deficiency syndrome scores were assessed. Other outcome measures included the number of retrieved oocytes and fertilization, high-quality embryo and clinical pregnancy rates. Follicular fluid was collected on the day of oocyte retrieval, and granulosa cell expression of phosphatidylinositide 3-kinases (PI3K), serine-threonine kinase (Akt) and forkhead box O3 (Foxo3a) mRNA were measured by reverse transcribed and quantitative real-time polymerase chain reaction.@*RESULTS@#Syndrome scores for pre- versus post-treatments decreased significantly (16.53±1.75 to 8.67±1.61) in the EA group (P<0.05), but showed no significant change in the control group (17.18±1.58 to 14.74±1.58). A significant difference in score change was found between the EA and control groups (P<0.05). High-quality embryo and clinical pregnancy rates were both increased in the EA group compared with the control group [69.15% (195/282) vs. 60.27% (176/292) and 66.67% (22/33) vs. 42.42% (14/33), respectively, P<0.05]. The fertilization rate was equivalent in EA and control groups. No difference was found in the number of retrieved oocytes between the two groups. Granulosa cell expression levels of PI3K and Akt mRNA were significantly increased in the EA group compared with the control group, while the expression of Foxo3a was reduced (all P<0.05).@*CONCLUSIONS@#For infertile patients with Shen deficiency syndrome undergoing IVF, EA for tonifying Shen as an adjunct treatment may alleviate clinical symptoms and improve the high-quality embryo rate. The EA-induced mechanism may involve regulation of PI3K/Akt/Foxo3a expression in granulosa cells to improve the developmental microenvironment of oocytes and inhibit granulosa cell apoptosis, possibly contributing to the improved clinical pregnancy rate (Registration No. ChiCTR 1800016217).

Clinical significance of serum prealbumin-bilirubin score (PALBI) in predicting posthepatectomy liver failure in patients with HBV-related hepatocellular carcinoma / 中华肝胆外科杂志

Objective To study the value of serum prealbumin-bilirubin score (PALBI) in predicting posthepatectomy liver failure (PHLF) for patients with HBV related hepatocellular carcinoma (HCC).Methods A retrospective study was conducted on 919 HBV-related HCC patients who underwent hepatectomy from September 2013 to December 2016 at the Affiliated Tumor Hospital of Guangxi Medical University.These patients were divided into a training cohort (n =689) and a validation cohort (n =230) using the 3 ∶ 1 matching principle.The training cohort was divided into the control group (n=546) and the PHLF group (n=143) according to whether PHLF occurred.The multivariate logistic regression model was used to analyze the factors related to PHLF in the training cohort,and then the PALBI score was established.The ability of the PALBI score to predict PHLF was evaluated by the area under the receiver operating characteristic curve (AUC) and compared with the Child-Pugh,model for end-stage liver disease (MELD),and albumin-bilirubin (ALBI) scores.Results Univariate and multivariate logistic regression analyses showed the factors including HBV-DNA≥ 103 IU/ml,total bilirubin,prealbumin,platelet count,AST,prothrombin time,intraoperative blood loss ≥400 ml and major liver resection were closely related to PHLF.The ability of the PALBI score (AUC =0.733) to predict PHLF preoperatively was superior to the ChildPugh score (AUC =0.562),the MELD score (AUC =0.652) and the ALBI score (AUC =0.683) in the entire training cohort.Similar results were obtained in the entire validation cohort (AUC:0.752 vs.0.599 vs.0.641 vs.0.678).To eliminate the effect of a small residual liver volume on PHLF,the ability of each of these scores in the training and validation cohorts to predict PHLF was calculated respectively in these 2 cohorts of patients who underwent only minor liver resection,and similar results were obtained.Conclusion The PALBI score was significantly superior to the Child-Pugh,MELD and ALBI scores in predicting PHLF in patients with HBV-related HCC who underwent liver resection.The PALBI score is a simple,non-invasive and reliable novel model in predicting PHLF.

Study on the dynamic changes of endothelial progenitor cells in peripheral blood and cognitive ability of rats with different degrees of traumatic brain injury / 天津医药

Objective To observe the dynamic changes of endothelial progenitor cells(EPCs)in peripheral blood and cognitive ability of rats with different degrees of traumatic brain injury (TBI). Methods A total of 28 male SD rats were randomly divided into 4 groups:sham group,mild traumatic brain injury group,moderate traumatic brain injury group and severe traumatic brain injury group,seven rats in each group.A hole was drilled on the right parietal skull(4.0 mm posterior from bregma and 3 mm lateral to the sagittal suture,hippocampal region)to expose the dura.Rats were subjected to different degrees of traumatic brain injury of 0.9,2.1,3.2 atm(1 atm=101.325 kPa).The dynamic changes of EPCs,white blood cell count(WBC)and platelets(PLT)in the circulating blood were measured before(0 h)and after TBI(3,6,24,48,72,168,240 and 336 h after trauma). Morris water maze (MWM) test was performed to record the escape latency and target quadrant change on day 21-25 after TBI in four groups. Results The number of circulating EPCs kept stable throughout the experiment in the sham group.The numbers of EPCs were significantly lower at 3 h after injury in mild,moderate and severe traumatic brain injury groups(17.4±3.1,15.6±5.0 and 23.6±3.0)than those in the sham group(53.6±7.9,P<0.05).The numbers of EPCs at 6 h after injury were increased rapidly,and which were significantly higher in the mild and moderate TBI group than those in sham group(P<0.05).Then the number of EPCs dropped to the normal level on 48 h after injury.The changes of EPCs was inconsistent with the WBC and PLT during the whole experiment.The positioning cruise experiment showed that the escape latency shortened over time in each group.The escape latency was longer in TBI group than that in sham group during the same period. The spatial probe test showed that the percentages of the target quadrant were significantly lower in the moderate and severe TBI groups than those in the sham group and the mild TBI group. Conclusion With the severity of traumatic brain injury,the cognitive ability reduces in model rats.The level of endothelial progenitor cells in circulating blood is related to the severity of the traumatic brain injury,and can be used as a marker to judge the prognosis.

Neuropathologic study of massive subcortical heterotopia / 中华病理学杂志

Objective@#To investigate the clinicpathologic features and probable mechanisms of massive subcortical heterotopia.@*Methods@#Clinical data, histologic features and neuropathologic data were analyzed in five cases of massive subcortical heterotopia collected from Xuanwu Hospital, Capital Medical University from January 2014 to October 2017.@*Results@#All five patients (three males and two females) had a history of refractory epilepsy with a mean period of 15.4 years (range 7 to 21 years). The median age at surgery was 28.6 years(range 20 to 39 years). Magnetic resonance imaging showed that the lesions were located in the temporal lobe (two cases), parietal lobe (one case), both temporal and occipital lobes (one case) and both temporal and parietal lobes (one case). Pathologic examination disclosed that massive gray matter in subcortical and deep white matter with various shape and size. Moreover, one case also showed subpial and periventricular heterotopias and polymicrogyria. Polymicrogyria or hippocampal sclerosis were seen in the remaining three cases. None of the five patients experienced seizure attacks during the follow-up period.@*Conclusions@#Heterotopia is malformations due to abnormal neuronal migration. Massive subcortical heterotopia due to widespread abnormal neuronal migration is relatively rare. The mechanism of heterotopia together with polymicrogyria needs further discussion.

Relationship between quantitative indices of carotid plaque from contrast-enhanced ultrasound and leukocytes in patients with acute large artery atherosclerotic stroke / 上海交通大学学报（医学版）

Objective·To investigate the relationship between quantitative indices of carotid plaques from contrast-enhanced ultrasound and leukocytes, and explore the value in the patients with acute large artery atherosclerotic stroke (LAAS). Methods·A total of 62 patients with LAAS and 48 matched control subjects hospitalized in Shanghai General Hospital, Shanghai Jiao Tong University from June 2016 to June 2017 were enrolled. Obvious carotid plaques were examined by contrast-enhanced ultrasound. The parameters of time-intensity curve i.e. peak (PTIC) and mean (MTIC), and the parameters of fitting curve i.e. peak (PFC), sharpness (SFC), and under the curve area (AUCFC) were obtained. These parameters were compared between the groups using two samples t tests. The correlations between the parameters and leukocyte counts were analyzed by Pearson correlation analysis. Results·① In LAAS group, the total leukocyte and neutrophil counts were higher than those of the control group, while the lymphocyte count was lower than that of the control group (P<0.05). ② The PTIC, MTIC, PFC, SFC and AUCFC were significantly larger in LAAS group than those in the control group, respectively (P<0.05).③ PTIC, MTIC and PFC were negatively correlated with lymphocytes, respectively (r=-0.291, -0.263 and -0.270, P<0.05). SFC and AUCFC were positively correlated with neutrophils, respectively (r=0.261 and 0.298, P<0.05). Conclusion·Quantitative indices of carotid plaques from contrast-enhanced ultrasound are associated with circulating leukocytes, and the association helps assess the vulnerability of the plaques.

Pharmacokinetics and Bioavailability in Vivo Rats of Daidai Flavonoids Lipid-Lowering Dropping Pills / 中国药学杂志

OBJECTIVE: To establish an UPLC-MS method for simultaneously determining the contents medical components of neohespiridin and naringin in rat plasma, meanwhile to investigate the pharmacokinetics for Daidai flavonoids lipid-lowering dropping pills and Daidai flavones extraction were compared in rats. METHODS: We are established an UPLC-MS method to simultaneously determine the content of effective components(neohesperidin and naringin) of Daidai fruit flavones lipid-lowering dropping pills in rat plasma, measured blood drug concentration in rats, fitted medicine curve, analyzed and compared the pharmacokinetic process in vivo of Daidai fruit flavones lipid-lowering dropping pills and Daidai fruit flavonoids extracts, to evaluate the oral bioavailability improvement of Daidai fruit flavones lipid-lowering dropping pills. RESULTS: The pharmacokinetics experimental results of rat gastric drug delivery with Daidai fruit flavonoids extract compared with that of rat with Daidai fruit flavones lipid-lowering dropping pills showed that the ρmax of neohesperidin in medicated serum is(1.68±0.02)extract and (5.54±0.09)dropping pillsmg·L-1, respectively; the ρmax of naringin is(1.50±0.05) extract and(4.83±0.10) dropping pillsmg·L-1, respectively; the ρmax and AUC0~∞ of Daidai fruit flavones lipid-lowering dropping pills were significantly higher than that of Daidai fruit flavonoids extraction(P<0.05), and MRT and t1/2 of Daidai fruit flavones lipid-lowering dropping pills were significantly shorter than that of Daidai fruit flavonoids extracts.With Daidai fruit flavonoids extract as reference, the relative bioavailability of neohesperidin and naringin in dropping pills were 278.52% and 258.59%, respectively. CONCLUSION: Daidai flavones dropping pill can significantly improve the medical components of neohespiridin and naringin oral bioavailability of Daidai flavones extraction.

Expression of hypoxia inducible factor 1αand glucose transporter 1 in lung adenocarcinoma and their clinical significances / 肿瘤研究与临床

Objective To investigate the expression of hypoxia inducible factor 1α (HIF-1α) and glucose transporter 1 (GLUT1) in lung adenocarcinoma and its correlation with tumor metastasis. Methods SP immunohistochemistry was used to detect GLUT1 and HIF-1α protein expression in 125 lung adenocarcinoma, including 41 cases without metastasis, 38 cases with lymphatic metastasis and 46 cases with brain metastasis. The correlation of GLUT1 and HIF-1α in lung adenocarcinoma metastasis was analyzed by using x 2 test and Pearson correlation analysis. Results Most lung adenocarcinoma were histologically heterogeneous, which contained more than one adenocarcinoma type. 73.2 % (30/41) cases were acinar predominant adenocarcinoma in lung adenocarcinoma without metastasis; 53.6 % (15/38) cases were acinar predominant adenocarcinoma and 26.3 % (10/38) cases were solid predominant adenocarcinoma in lung adenocarcinoma with lymphatic metastasis; 47.8 % (22/46) cases were papillary predominant adenocarcinoma and 34.8 % (16/46) cases were solid predominant adenocarcinoma in lung adenocarcinoma with brain metastases. The expression level of GLUT1 and HIF-1α in lung adenocarcinoma with lymphatic metastasis group was higher than that of the group without tumor metastasis (P< 0.05); the expression of GLUT1 and HIF-1α were positively correlated (r=0.407, P=0.000). Conclusions Papillary adenocarcinoma is the most histological type in lung adenocarcinoma with brain metastasis, suggesting that papillary adenocarcinoma is more prone to brain metastasis. The expression of GLUT1 and HIF-1α play an important role in lymph node metastasis and brain metastasis of lung adenocarcinoma.

The clinical and pathological features of 85 cases with positive cerebrospinal fluid cytology by thin-layer centrifugal cytological test / 中华内科杂志

Objective To evaluate cytological test of cerebrospinal fluid in the diagnosis of meningeal dissemination of tumor cells.Methods The clinical and imaging features of 85 cases with tumor cells diagnosed by thin-layer centrifugal cytological test of cerebrospinal fluid were retrospectively reviewed.The characteristics of cellular morphology and immunocytochemical staining were analyzed.Results The main presentations of all the patinets was meningeal irritation and neurological dysfunction.The features of the brain MRI were meningeal thicking and enhancement,intracranial abnormal signals and intracranial space occupying lesion in part of the patients.Atypical cells were found in 84 cases (98.8％) with the first sample test and immunocytochemical staining was conducted in 48 cases to identify the tissue origin.Meningeal carcinomatosis was shown to be the majority with lung cancer as the dominated tissue type and adenocarcinoma as the most common histological type.Others were lymphatic hematopoietic system (13 cases),melanomas (5 cases),primitive neuroectodermal tumor (3 cases) and glioma (1 case).In addition,12 cases were only proved to be cancer by cytological test of cerebrospinal fluid.Conclusion The thin-layer centrifugal cytological test of cerebrospinal fluid has a relatively high accuracy for detecting disseminated tumor cells of meninges and could be of great help to identify the source and type of lesion with immunocytochemical staining.

Improvement of the oocyte quality with electroacupuncture in infertility patients of kidney deficiency pattern / 中国针灸

<p><b>OBJECTIVE</b>To explore the impact and effect mechanism of electroacupuncture (EA) on oocyte quali ty in the patients with infertility of kidney deficiency pattern.</p><p><b>METHODS</b>Sixty-six cases differentiated as kidney de ficiency and with in vitro fertilization-embryo transplantation (IVF-ET), aged fromnt 35 to 42 years were rando- mized into an observation group and a control group, 33 cases in each one. The IVF-ET therapy of the long proto- col with gonadotrophin releasing hormone agonist was adopted in the two groups. In the observation group. on the 5th day of menstruation in IVF cycle, EA was applied to Sanyinjiao (SP 6). Zigong (EX CA 1), Zhongji (CV 3) and Guanyuan (CV 4). In the control group, the sham-acupuncture was applied to the same acupoints. The treatment was given once every two days till the date of egg collection and the needles were retained for 30 min each time. The change in the score of kidney deficiency syndrome, the high-quality oocyte rate, the high-quality embryo rate and clinical pregnant rate were observed in the two groups. The levels of insulin-like growth factor-i (IGF-1) and IGF-2 in follicular fluid and the serum β-endorphin β-EP) on the date of egg collection and the correlation with oocyte quality were compared bIetween the two groups.</p><p><b>RESULTS</b>1) In the observation group, the kidney deficiency syndrome score after treatment was reduced apparently as compared with that before treatment (P<0. 05), the score after treatment in the observation group was reduced much more apparently as compared with the control group (P<0.05). 2) The high-quality egg rate and the high-quality embryo rate in the observation group were both higher than those in the control group [81.3% (161/198) vs 57.6% (98/170), 59.8% (58/97) vs 37.7% (26/69), both P<0.05]. 3) Compared with the control group. the levels of IGF-1 and IGF-2 in follicular fluid and serum β-EP on the day of egg collection were all increased obviously in the observation group (all P<0. 05). 4) The levels of IGF-1 and IGF-2 in follicular fluid and serum β-EP presented the linear positive correlation with the high-quality egg rate.</p><p><b>CONCLUSION</b>EA effectively improves the expressions of IGF in follicular fluid and serum β-EP, increases the high-quality egg rate and high-quality embryo rate and relieves the symptoms of kidney deficiency.</p>

Evaluation of group clustering synchronization release of Daidai Flavones Dropping Pills based on characteristic spectrum / 中草药

Objective: Based on the advantages of representation of herb components group clustering by characteristic spectrum integrity, to study the in vitro dissolution behavior of Daidai Flavones Dropping Pills (DFDP), and to evaluate the synchronization release situation of group clustering. Methods: Rotating basket method and HPLC characteristic spectrum were employed to evaluate the group clustering dissolution and the release characteristics of DFDP in different dissolution media (pH 1.2 hydrochloric acid solution, pH 4.5 acetic acid-sodium acetate buffer, pH 6.8 phosphate buffer, and distilled water). The single exponential, logarithmic distribution and Weibull equation model were applied to fit the dissolution curves. Results: The similarity factor (f2) of the dissolution curves of nine common peak components in characteristic spectrum of DFDP was over 50; In addition the f2 of neohesperidin and naringin was 94.86, which indicated that the group clustering of DFDP had similar dissolution curves and synchronization release characteristics. Meanwhile the dissolution mechanism of group clustering of nine common peak activity composition was following the Weibull equation model. Conclusion: The established method is simple, rapid, and stable, which provides an experimental basic for in vitro analysis and quality evaluation of DFDP.

Application of light invasive treatment of endometrial in husband sperm intrauterine insemination patients / 中国医师进修杂志

Objective To discuss the effect of light invasive treatment of endometrial in husband sperm intrauterine insemination outcomes.Methods A total of 248 patients receiving husband sperm intrauterine insemination were divided into two groups by random digits table method.The patients in light invasive treatment of endometrial group (138 cases with 246 cycles) were performed with light invasive treatment of endometrial,and the patients in control group (110 cases with 201 cycles) were not perfomed with light invasive treatment of endometrial.Human chorionic gonadotropin day of endometrial thickness,intrauterine insemination tube placed successfully or not,whether fertilization tube bloody and clinical pregnancy rates and so on were compared between two groups.Results There was no significant difference in human chorionic gonadotropin day of endometrial thickness between two groups (P ＞ 0.05).The success rate of intrauterine insemination tube placement in light invasive treatment of endometrial group was 78.5％ (193/246),which was higher than that in control group (65.2％,131/201),and there was significant difference (P ＜ 0.05).The intrauterine insemination tube bloody rate in light invasive treatment of endometrial group was 13.4％ (33/246),which was lower than that in control group (34.8％,70/201),and there was significant difference (P ＜ 0.05).The pregnancy rate in light invasive treatment of endometrial group was 31.9％ (44/138),which was higher than that in control group (18.2％,20/110),and there was significant difference (P ＜ 0.05).There were no significant differences in ectopic pregnancy rate and abortion rate between two groups (P ＞ 0.05).Conclusion Through light invasive treatment of endometrial the husband sperm intrauterine insemination outcomes can be improved.

Research progresses on improving follicle improvement quality by traditional Chinese Medicine / 国际中医中药杂志

According to the relevant literature, combined with the clinical experience of Professor Lianfang, the rule of traditional Chinese medicine in the treatment of abnormal follicular development was studied. The etiology and pathogenesis, syndrome differentiation and treatment, special formula, the combination of traditional Chinese medicine and other therapy for abnormal follicular development were sorted and summarized.