Optimization and identification of a low density and high purity method for primary hippocampal neuron culture from fetal rats / 解剖学报

Objective To establish a low density, high purity and high stability in vitro culture method of primary hippocampal neurons of fetal rats by co-culturing hippocampal and cortical cells, so as to obtain higher purity and better vitality of primary hippocampal neurons disease. Methods The fetal rat hippocampal tissue was isolated from 16-18 days pregnant SD rats, then cut and digested by 0.125% trypsin. The obtained cell suspension was filtered by 200 mesh cell sieve, and then the obtained cell suspensions were then inoculated into the inner layer and outer ring of the culture plate in a surrounding form. They were co-cultured in DMEM/F12 medium containing 10% horse serum. After 4-6 hours of cell adhesion, the culture medium was changed to maintenance medium (Neurobasal+2% B27+0.5 mmol/L glutamine). Then the cell viability was detected with CCK-8 kit and the purity of hippocampal neurons was detected by immunofluorescent staining. Results Hippocampal neurons grew well and formed crisscross neural networks after 5 days. And it could survive for 3 weeks. The purity of hippocampal neurons was up to 98%. Conclusion The method of co-culturing hippocampal and cortical cells can obtain high-purity, high activity, high survival rate, and high stability primary hippocampal neurons from fetal rats, which can provide certain experimental conditions for the study of hippocampal neuron related diseases in the nervous system and is worthy of promotion and application.

Effects of transient receptor potential vanilloid 4 inhibitor HC067047 on anxiety-like behavior in mice induced by lipopolysaccharide / 解剖学报

Objective To investigate the effect of transient receptor potential vanilloid 4 (TRPV4) inhibitor HC067047 on anxiety-like behavior in mice induced by lipopolysaccharide (LPS). Methods Totally 48 male C57BL/6 mice were randomly divided into control group (NS), model group (LPS) and drug intervention group (HC + LPS). Anxiety mouse model was established by intraperitoneal injection of 0.83 mg/kg LPS. The HC + LPS group was intraperitoneally injected with HC067047 (10 mg/kg) 30 minutes before LPS injection, and the NS group and LPS group were injected with equal volume of normal saline. Open field test and social interaction experiments were used to detect anxiety-like behaviors in each group of mice; Immunohistochemical chemistry and Western blotting were used to detect the expression of TRPV4, inducible nitric oxide synthase (iNOS), neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS) in the hippocampus. Results Immunohistochemical and Western blotting experiments showed that, compared with the NS group, the expression of TRPV4 in the hippocampus of the LPS group was significantly up-regulated (P<0.0001); In the open field test, compared with the NS group, the total distance (P < 0.0001), the distance in the central area (P<0.01) and the time of in the central area mice in the LPS group reduced significantly (P< 0.01). HC067047 intervention reversed the activities of LPS model mice total distance (P < 0.05), the distance of activities in the central area (P < 0.001) and the time of in the central area (P < 0.01); In the social interaction test, compared with the NS group, the interaction time the unfamiliar mice reduced significantly in LPS group (P<0.01), which was reversed by HC067047 treatment (P< 0.01); Western blotting detection revealed that the expression of hippocampal iNOS (P<0.05), nNOS (P < 0.001), and eNOS (P < 0.001) in the LPS group were significantly higher than the NS group, which reduced remarkably by HC067047 treatment (iNOS P < 0.05, nNOS P < 0.01 and eNOS P < 0.01). Conclusion Inhibiting the expression of TRPV4 can improve the anxiety-like behavior, and this process may be related to anti-oxidative stress.

Application of "major scientific issues and engineering technology difficulties in traditional Chinese medicine(2019-2021)" in national science and t echnology layout / 中国中药杂志

In order to judge the future development trend of science and technology, plan ahead and lay out the frontier technology fields and directions, China Association of Chinese Medicine(CACM) has launched consultation projects for collecting "major scienti-fic issues and engineering technology difficulties in traditional Chinese medicine(TCM)" for the industry for three consecutive years since 2019. Up to now, 18 projects have been selected as major issues for research, and some experience and achievements have been made. These projects have been applied in important scientific and technological work such as scientific and technological planning and deployment at all levels of national, local, and scientific research institutions, the selection and cultivation of major national scientific and technological projects, and the construction of innovation bases, giving full play to the role of the think tank advisory committee of CACM. This study reviewed the selection of major issues for the first time, systematically combed its application in the national layout of science and technology, and put forward the existing problems and improvement suggestions, aiming to provide new ideas for further improving the selection of major issues and research direction, providing a theoretical basis and decision support for the national scientific and technological layout in the field of TCM, and promoting scientific and technological innovation to facilitate the high quality development of TCM.

Precise application of Beichaihu and Nanchaihu in classical formulas / 中国中药杂志

To maintain the precision and stability of the efficacy of classical formulas, this study compared the origins and specifications of Bupleuri Radix and revealed the precise application regularity of Bupleurum chinense(Beichaihu) and Bupleurum scorzonerifolium(Nanchaihu) in classical formulas. The efficacy and indications of formulas with Bupleuri Radix as the sovereign drug in the Treatise on Cold Damage and Miscellaneous Diseases(Shang Han Za Bing Lun) were investigated. The difference in the efficacy of Bupleuri Radix as well as the differences in the chemical composition, and liver-protecting and lipid-lowering effects of the decoctions of Beichaihu and Nanchaihu were analyzed with LC-MS technology based on the CCl_4-induced liver injury model in mice and sodium oleate-induced HepG2 hyperlipidemia cell model. The results showed that seven classical formulas with Bupleuri Radix as the sovereign drug in the Treatise on Cold Damage and Miscellaneous Diseases were mainly used in the treatment of digestive, metabolic, immune, circulatory, and other diseases. Bupleuri Radix mainly played the functions of protecting the liver, benefiting the gallbladder, and lowering the lipid, and had different focuses in different formulas. There were 14 differential components in the decoctions of Beichaihu and Nanchaihu, and the chemical structures of 11 components were identified, including 10 saponins and one flavonoid. The results of the liver-protecting efficacy experiment showed that compared with the Nanchaihu decoction, Beichaihu decoction could reduce the serum aspartate aminotransferase(AST) activity in liver injury model mice(P<0.01). The results of the lipid-lowering efficacy experiment proved that Beichaihu and Nanchaihu decoctions both showed highly significant differences in lowering the total cholesterol(TC) and triglyceride(TG) content in HepG2 cells(P<0.01), and Nanchaihu decoction was superior to Beichaihu decoction in lowering the lipid. The results of this study preliminarily proved that there were differences in chemical composition, and liver-protecting and lipid-lowering effects of Beichaihu and Nanchaihu decoctions, indicating that it was necessary to determine the precise origin of Bupleuri Radix in the clinical formulation of traditional Chinese medicine. The study provides a scientific basis for both precise clinical medication and purpose-based accurate quality evaluation of traditional Chinese medicine in clinical application.

Systematic review and Meta-analysis of efficacy and safety of Tangmaikang Granules in treatment of diabetic peripheral neuropathy / 中国中药杂志

This study aimed to explore the efficacy and safety of Tangmaikang Granules in the treatment of diabetic peripheral neuropathy(DPN). PubMed, Cochrane Library, EMbase, SinoMed, CNKI, Wanfang and VIP were retrieved for randomized controlled trial(RCT) of Tangmaikang Granules in the treatment of DPN. Cochrane handbook 5.3 was used to evaluate the quality of the inclu-ded studies, and RevMan 5.4.1 and Stata 15.1 were employed to analyze data and test heterogeneity. GRADEpro was used to assess the quality of each outcome index. Clinical effective rate was the major outcome index, while the improvement in numbness of hands and feet, pain of extremities, sluggishness or regression of sensation, sensory conduction velocity(SCV) and motor conduction velocity(MCV) of median nerve and peroneal nerve, fasting blood glucose(FBG), 2 h postprandial blood glucose(2hPBG), and glycated hemoglobin(HbA1c) and incidence of adverse reactions were considered as the minor outcome indexes. A total of 19 RCTs with 1 602 patients were eventually included. The Meta-analysis showed that the improvements in clinical effective rate(RR=1.45, 95%CI[1.32, 1.61], P<0.000 01), pain of extremities(RR=1.70, 95%CI[1.27, 2.27], P=0.000 3), MCV of peroneal nerve(MD=4.08, 95%CI[3.29, 4.86], P<0.000 01) and HbA1c(SMD=-1.23, 95%CI[-1.80,-0.66], P<0.000 1) of Tangmaikang Granules alone or in combination in the experimental group were better than those in the control group. Compared with the conditions in the control group, numbness of hands and feet(RR=1.42, 95%CI[1.12, 1.80], P=0.003), sluggishness or regression of sensation(RR=1.41, 95%CI[1.05, 1.91], P=0.02), SCV of median nerve(MD=4.59, 95%CI[0.92, 8.27], P=0.01), SCV of peroneal nerve(MD=4.68, 95%CI[3.76, 5.60], P<0.000 01) and MCV of median nerve(MD=5.58, 95%CI[4.05, 7.11], P<0.000 01) of Tangmaikang Granules in combination in the experimental group were improved by subgroup analysis. The levels of FBG(MD=-0.57, 95%CI[-1.27, 0.12], P=0.11) and 2hPBG(MD=-0.69, 95%CI[-1.70, 0.33], P=0.18) in the experimental group were similar to those in the control group after treatment with Tangmaikang Granules alone or in combination. There was no difference in the safety(RR=1.28, 95%CI[0.58, 2.82], P=0.54) of Tangmaikang Granules in the treatment of DPN between the experimental group and the control group. Tangmaikang Granules could significantly increase clinical effective rate and nerve conduction velocity as well as improve symptoms of peripheral nerve and blood glucose level, and no serious adverse reactions were identified yet. Further validation was needed in future in large-sample, multicenter, high-quality RCTs.

Recent research on the relationship between pulmonary microbiome and asthma endotypes in children / 中国当代儿科杂志

Bronchial asthma is not considered a singular disease, but rather a collection of syndromes with multiple phenotypes and mechanisms that involve various signaling pathways. It typically emerges during the preschool years, and its etiology is intricate and diverse. In recent years, the advancement of high-throughput sequencing technology has revealed that early alterations in lung microbiota may be associated with asthma incidence and progression. Moreover, significant variations in lung microbiota have been observed among different airway inflammation profiles, known as asthma endotypes. Hence, a comprehensive understanding of the characteristics of lung microbiota in children with asthma can aid in managing disease progression and improving long-term prognosis. Additionally, such insights may spark novel approaches to diagnosing and treating childhood asthma.

Effect of Yunkang Oral Solution on pregnant mice with spleen deficiency syndrome / 中国中药杂志

This study aimed to investigate the therapeutic effect of Yunkang Oral Solution on the improvement of spleen deficiency and pregnancy outcomes in pregnant mice with spleen deficiency syndrome induced by irregular diet and over consumption of cold and bitter foods. To simulate human irregular diet and over consumption of cold and bitter foods leading to spleen deficiency, the pregnant mice with spleen deficiency syndrome were prepared using an alternate-day fasting and high-fat diet combined with oral administration of Sennae Folium. During the experiment, spleen deficiency-related indicators and diarrhea-related parameters were measured. Gastric and intestinal motility(gastric emptying rate and intestinal propulsion rate) were evaluated. The levels of serum ghrelin, growth hormone(GH), gastrin(Gas), total cholesterol(TC), low-density lipoprotein cholesterol(LDL-c), chorionic gonadotropin β(β-CG), progesterone(P), and estradiol(E_2) were measured. Intestinal barrier function in pregnant mice with spleen deficiency syndrome was assessed. Conception rate, ovarian coefficient, litter-bearing uterine coefficient, number of live fetuses, average fetal weight, and fetal length were calculated. The results showed that Yunkang Oral Solution significantly improved spleen deficiency-related indicators and diarrhea in pregnant mice with spleen deficiency syndrome, increased gastric emptying rate and intestinal propulsion rate, elevated the levels of gastrointestinal hormones(ghrelin, GH, and Gas) in the serum, and reduced lipid levels(TC and LDL-c), thereby improving lipid metabolism disorders. It also improved colonic tissue morphology, increased the number of goblet cells, and promoted the mRNA and protein expression of occludin and claudin-1 in colonic tissues, thereby alleviating intestinal barrier damage. Yunkang Oral Solution also regulated the levels of pregnancy hormones(β-CG, P, and E_2) in the serum of pregnant mice with spleen deficiency syndrome. Moreover, it increased the conception rate, ovarian coefficient, litter-bearing uterine coefficient, number of live fetuses, average fetal weight, and fetal length. These findings suggest that Yunkang Oral Solution can improve spleen deficiency-related symptoms in pregnant mice before and during pregnancy, regulate pregnancy-related hormones, and improve pregnancy outcomes.

Esketamine reduces inflammatory damage in HT22 cells and ferroptosis mechanisms / 中国药理学通报

Aim To investigate the effect of esketamine(ESK)on lipopolysaccharide(LPS)-induced damage to HT22 cells(mouse hippocampal neuron cells)and the underlying mechanism. Methods After ESK pretreatment for 2 h and then LPS treatment for 24 h, Western blot was used to detect high mobility group box-1(HMGB1), long chain acyl CoA synthetase 4(ACSL4), prostaglandin-endoperoxide synthase 2(PTGS2), transferrin receptor 1(TFR1), ferroportin(FPN)and ferritin expression. ELISA was used to detect the expression of inflammatory protein interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α). DHE fluorescent was probed to detect the changes in intracellular reactive oxygen species(ROS). MDA kit was used to detect intracellular lipid oxidation levels. FerroOrange fluorescent was probed to detect intracellular divalent iron ion levels. Electron microscopy was used to observe the changes in mitochondrial ultrastructure. Results Compared with the normal group, the levels of ROS, lipid peroxidation and Fe

Early predictive value of high density lipoprotein cholesterol for secondary acute kidney injury in sepsis patients / 中华烧伤杂志

Objective: To investigate the changes of high density lipoprotein cholesterol (HDL-C) in sepsis patients and its early predictive value for secondary acute kidney injury (AKI) in such patients. Methods: A retrospective case series study was conducted. From June 2019 to June 2021, 232 sepsis patients who met the inclusion criteria were admitted to the Second Hospital of Hebei Medical University, including 126 males and 106 females, aged 24 to 71 years. According to whether complicating secondary AKI, the patients were divided into non-AKI group (n=158) and AKI group (n=74). Data of patients between the two groups were compared and statistically analyzed with independent sample t test or chi-square test, including the sex, age, body mass index (BMI), body temperature, heart rate, primary infection site, combined underlying diseases, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score and sepsis-related organ failure assessment (SOFA) score at admission, and the serum levels of C-reactive protein (CRP), procalcitonin, creatinine, cystatin C, and HDL-C measured at diagnosis of sepsis. The multivariate logistic regression analysis was performed on the indicators with statistically significant differences between the two groups to screen the independent risk factors for developing secondary AKI in 232 sepsis patients, and the joint prediction model was established based on the independent risk factors. The receiver operating characteristic (ROC) curve of the independent risk factors and the joint prediction model predicting secondary AKI in 232 sepsis patients were drawn, and the area under the curve (AUC), the optimal threshold, and the sensitivity and specificity under the optimal threshold were calculated. The quality of the above-mentioned AUC was compared by Delong test, and the sensitivity and specificity under the optimal threshold were compared using chi-square test. Results: The sex, age, BMI, body temperature, heart rate, primary infection site, combined underlying diseases, and CRP level of patients between the two groups were similar (P>0.05). The procalcitonin, creatinine, cystatin C, and scores of APACHE Ⅱ and SOFA of patients in AKI group were all significantly higher than those in non-AKI group (with t values of -3.21, -16.14, -12.75, -11.13, and -12.88 respectively, P<0.01), while the HDL-C level of patients in AKI group was significantly lower than that in non-AKI group (t=6.33, P<0.01). Multivariate logistic regression analysis showed that creatinine, cystatin C, and HDL-C were the independent risk factors for secondary AKI in 232 sepsis patients (with odds ratios of 2.45, 1.68, and 2.12, respectively, 95% confidence intervals of 1.38-15.35, 1.06-3.86, and 0.86-2.56, respectively, P<0.01). The AUCs of ROC curves of creatinine, cystatin C, HDL-C, and the joint prediction model for predicting secondary AKI in 232 sepsis patients were 0.69, 0.79, 0.89, and 0.93, respectively (with 95% confidence intervals of 0.61-0.76, 0.72-0.85, 0.84-0.92, and 0.89-0.96, respectively, P values all below 0.01); the optimal threshold were 389.53 μmol/L, 1.56 mg/L, 0.63 mmol/L, and 0.48, respectively; the sensitivity under the optimal threshold were 76.6%, 81.4%, 89.7%, and 95.5%, respectively; the specificity under the optimal threshold values were 78.6%, 86.7%, 88.6%, and 96.6%, respectively. The AUC quality of cystatin C was significantly better than that of creatinine (z=2.34, P<0.05), the AUC quality and sensitivity and specificity under the optimal threshold of HDL-C were all significantly better than those of cystatin C (z=3.33, with χ2 values of 6.43 and 7.87, respectively, P<0.01) and creatinine (z=5.34, with χ2 values of 6.32 and 6.41, respectively, P<0.01); the AUC quality and sensitivity and specificity under the optimal threshold of the joint prediction model were all significantly better than those of creatinine, cystatin C, and HDL-C (with z values of 6.18, 4.50, and 2.06, respectively, χ2 values of 5.31, 7.23, 3.99, 6.56, 7.34, and 4.00, respectively, P<0.05 or P<0.01). Conclusions: HDL-C level in sepsis patients with secondary AKI is significantly lower than that in patients without secondary AKI. This is an independent risk factor for secondary AKI in sepsis patients with a diagnostic value being superior to that of creatinine and cystatin C. The combination of the aforementioned three indicators would have higher predicative valuable for secondary AKI in sepsis patients.

Application of acellular bovine pericardium patch in implant based immediate breast reconstruction / 中华外科杂志

Objective: To examine the clinical effect of acellular bovine pericardium patch in implant based immediate breast reconstruction. Methods: The clinicopathological information of 141 breast cancer patients, who admitted to Department of Breast Reconstruction and Oncoplastic Surgery, Tianjin Medical University Cancer Hospital, underwent immediate mammoplasty with implants combined with acellular bovine pericardium patches were analyzed from June 2016 to October 2019. All patients were female, with the age of (38.8±8.5) years (range: 13 to 60 years). The body mass index was (21.9±2.5) kg/m2 (range: 16.0 to 32.3 kg/m2). There were 39 cases of duct carcinoma in situ, 46 cases of stage Ⅰ, 40 cases of stage Ⅱ and 16 cases of stage Ⅲ. All patients received nipple-areola-sparing mastectomy or skin-sparing mastectomy with sentinel lymph node biopsy or axillary lymph node dissection, and prosthesis implantation with sub-pectoralis combined with breast patch. The correlation of clinicopathological characters and complications was assessed by t test, χ2 test, Fisher's exact probability method and Logistic regression. Pre-and post-operative aesthetic, quality of life scores were recorded. Results: The operation time (M(IQR)) was 3.6(1.5) hours (range: 3.0 to 6.5 hours). The early postoperative complication rate was 22.0% (31/141), prosthesis removal was the main postoperative complication, accounting for 64.5% (20/31) of the total complications, of which 15 cases occurred in the first 30 patients. The follow-up time was 28(8) months (range: 20 to 53 months), The most frequent long-term complications were capsular contracture and implant displacement, with the incidence of 11.2% (14/125) and 10.4% (13/125), respectively. Multivariate analysis showed that prosthesis volume ≥300 ml (OR=8.173, 95%CI: 1.302 to 51.315, P=0.021) and peri-areolar incision (OR=7.809, 95%CI: 2.162 to 28.211, P<0.01) were independent relative factors for the occurrence of short-term postoperative local complications. After 2 years of operation, the score of breast appearance satisfaction was 71.7±15.5, postoperative effect satisfaction was 90.4±9.5, psychological satisfaction was 90.7±17.1, sexual satisfaction was 70.1±25.1. The immediate postoperative satisfaction rate at discharge was 95.4% (134/141), and 17.6% (22/125) of patients had the intention to received revision surgery. Conclusions: Prosthesis volume ≥300 ml and peri-areolar incision were independent realtive factors for short-term local complications after bovine pericardium patch combined with prosthesis implantation in the immediate breast reconstruction. After completing the learning curve, the postoperative complications of the procedure could be decreased.

Association of CDH11 with Autism Spectrum Disorder Revealed by Matched-gene Co-expression Analysis and Mouse Behavioral Studies / 神经科学通报·英文版

A large number of putative risk genes for autism spectrum disorder (ASD) have been reported. The functions of most of these susceptibility genes in developing brains remain unknown, and causal relationships between their variation and autism traits have not been established. The aim of this study was to predict putative risk genes at the whole-genome level based on the analysis of gene co-expression with a group of high-confidence ASD risk genes (hcASDs). The results showed that three gene features - gene size, mRNA abundance, and guanine-cytosine content - affect the genome-wide co-expression profiles of hcASDs. To circumvent the interference of these features in gene co-expression analysis, we developed a method to determine whether a gene is significantly co-expressed with hcASDs by statistically comparing the co-expression profile of this gene with hcASDs to that of this gene with permuted gene sets of feature-matched genes. This method is referred to as "matched-gene co-expression analysis" (MGCA). With MGCA, we demonstrated the convergence in developmental expression profiles of hcASDs and improved the efficacy of risk gene prediction. The results of analysis of two recently-reported ASD candidate genes, CDH11 and CDH9, suggested the involvement of CDH11, but not CDH9, in ASD. Consistent with this prediction, behavioral studies showed that Cdh11-null mice, but not Cdh9-null mice, have multiple autism-like behavioral alterations. This study highlights the power of MGCA in revealing ASD-associated genes and the potential role of CDH11 in ASD.

Isoflavones from Sojae Semen Praeparatum Regulate Lipid Metabolism in Atherosclerotic Mice Through PPARγ/LXRα/ABCA1 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo study the effect of isoflavones from Sojae Semen Praeparatum （ISSP） on lipid metabolism in atherosclerotic mice， and decipher the underlying mechanism via the peroxisome proliferator-activated receptor gamma/liver X receptor alpha/ATP-binding cassette transporter A1 （PPARγ/LXRα/ABCA1） signaling pathway. MethodFifty ApoE-/- mice were randomly assigned into the model group， western medicine （atorvastatin calcium， 3.03 mg·kg-1） group， and low-， medium-， and high-dose ISSP （2.5， 5， 10 mg·kg-1， respectively） groups， with 10 rats in each group. Atherosclerosis model mice were established by bilateral ovariectomy and feeding high-fat diet. Another 10 ApoE-/- mice receiving ovariectomy and high-fat diet were taken as the sham group. Some mice died of postoperative infection， and finally 6 mice were included in each group. One week after operation， each group was administrated with corresponding drugs or equivalent amount of normal saline. After 12 weeks， the levels of triglyceride （TG）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， and non-esterified fatty acids （NEFAs） in serum and liver tissue were measured. The levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in serum were detected by enzyme-linked immunosorbent assay （ELISA）. Hematoxylin-eosin （HE） staining and oil red O staining were used for observation of aortic plaque formation and liver lipid deposition. The mRNA and protein levels of PPARγ， LXRα， ABCA1， and ATP-binding cassette transporter G1 （ABCG1） in liver were determined by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. ResultCompared with the sham group， the modeling of atherosclerosis increased the aortic plaque area （P<0.01）， elevated the serum TC， TG， LDL-C， TNF-α， and IL-6 levels （P<0.01）， decreased the level of HDL-C （P<0.01）， increased the liver index （P<0.05） and the levels of TC， TG， and NEFAs in liver （P<0.01）， and caused obvious hepatic fat vacuoles and lipid deposition. In addition， the modeling down-regulated the mRNA levels of PPARγ， LXRα， ABCA1 in liver （P<0.05， P<0.01），and regulated the mRNA and protein levels of ABCG1（P<0.05， P<0.01）. Compared with the model group， atorvastatin calcium and middle-， high-dose ISSP reduced the serum TC， TG， LDL-C， TNF-α， and IL-6 levels （P<0.01）， decreased the liver index （P<0.01）， alleviated the liver fat vacuoles and lipid deposition， and increased the levels of TC， TG， and NEFAs in the liver （P<0.05， P<0.01）. Furthermore， they up-regulated the mRNA and protein levels of PPARγ， LXRα， ABCA1， and ABCG1 in the liver （P<0.05， P<0.01）. ConclusionISSP may regulate lipid metabolism through PPARγ/LXRα/ABCA1 signaling pathway to down-regulate the expression of inflammatory cytokines in serum and alleviate liver lipid deposition， thereby suppressing the formation of atherosclerotic plaque.

Macrophage Polarization and Anti-tumor Mechanism of Chinese Medicine：A Review / 中国实验方剂学杂志

Macrophages are natural immune cells with strong plasticity. The polarization of macrophages mainly responds to stimuli in the microenvironment by changing their phenotype and related functions. In recent years， studies have found that the polarization of macrophages is involved in the occurrence and development of various diseases such as bone arthritis， skin diseases， diabetes， coronary heart disease， breast cancer， colorectal cancer， and lung cancer， especially the metastasis of malignancies and drug resistance， through multiple signaling pathways， including nuclear factor kappa-B（NF-κB）， c-Jun N-terminal kinase（JNK）， protein kinase B （Akt）， mitogen-activated protein kinase （MAPK）， signal transducer and activator of transcription 6 （STAT6）， Wnt/β-catenin， and mammalian target of rapamycin （mTOR） and regulatory factors， such as granulocyte-macrophage colony-stimulating factor （GM-CSF）， interleukin （IL）-4， IL-10， transforming growth factor （TGF）-β， tumor necrosis factor（TNF）-α， and interferon-γ（IFN-γ）. Chinese medicine is also pivotal in the prevention and treatment of malignancies. In recent years， therefore， the specific anti-tumor mechanism of Chinese medicine and its active ingredients has become a research hotspot. The tumor microenvironment is crucial to the occurrence and development of tumors. The polarization of tumor-associated macrophages is involved in the proliferation， apoptosis， and metastasis of tumor cells. Therefore， targeted regulation of the polarization of tumor-associated macrophages is a potential target for clinical treatment of malignancies. Based on the research articles published in the past three years， this article reviewed macrophage polarization and the anti-tumor mechanism of Chinese medicine from four perspectives， i.e.， macrophage polarization， related pathways and regulatory factors of macrophage polarization， macrophage polarization and breast cancer， colorectal cancer， and lung cancer， and macrophage polarization and anti-tumor effects of Chinese medicine， active ingredients of Chinese medicine， and self-formulated prescriptions/classic prescriptions. This study is expected to provide certain ideas for the clinical treatment， basic research， and development of new Chinese medicine in the treatment of tumors.

Efficacy of Qizi Yusi Pill on Pregnancy Outcomes in Women of Advanced Reproductive Age: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial / 中国结合医学杂志

OBJECTIVE@#To evalvate efficacy of Qizi Yusi Pills (QYP), a Chinese medicine compound preparation, on in vitro fertilization-embryo transfer (IVF-ET) in women of advanced reproductive age.@*METHODS@#This multicenter, randomized, double-blind, placebo-controlled trial was conducted from June 2018 to October 2019. A total of 124 patients were randomly allocated to either the QYP group or the placebo group using a stratified block randomization design, with 62 patients in each group. All patients completed controlled ovarian stimulation using a standard gonadotropin-releasing hormone agonist (GnRH-a) long protocol. As the QYP group, QYP was administered while the control group received placebo. QYP and placebo were administered for a total of 24 to 30 days from the day of GnRH-a pituitary downregulation to transvaginal oocyte retrieval. Both medications were taken orally at doses of 10 g three times each day. The primary outcome was cumulative pregnancy rate, and the secondary outcomes were periodic medication, follicular status, serum hormone and endometrial receptivity. Follow-up continued until 4 weeks after delivery. Maternal and neonatal complications, such as gestational diabetes, were also observed.@*RESULTS@#Overall, 119 patients completed the study, 60 in the QYP group and 59 in the placebo group. Per protocol (PP) analysis revealed that 6-month cumulative pregnancy rate in the QYP group was significantly higher than that in the placebo group [43.33% (26/60) vs. 25.42% (15/59), P=0.040). Additionally, more oocytes were retrieved from the QYP group than those from the placebo group (8.95 ± 3.12 vs. 7.85 ± 1.91, P=0.022). Moreover, the endometrial thickness of HCG day in the QYP group was significantly higher than that in the placebo group (11.78 ± 2.27 mm vs. 10.68 ± 2.07 mm, P=0.012). Maternal and neonatal complications between the two groups were not significantly different (P>0.05). Intention-to-treat analysis was in line with PP results.@*CONCLUSIONS@#QYP can enhance ovarian reserve capacity and ovarian response, and possibly promote endometrial receptivity. QYP effectively improves cumulative pregnancy rates in older patients (⩾35 years) undergoing IVF-ET. (Registration No. ChiCTR1800014427).

The Influence of Diabetes, Hypertension, and Hyperlipidemia on the Onset of Age-Related Macular Degeneration in North China: The Kailuan Eye Study / 生物医学与环境科学（英文）

Objective@#To analyze the prevalence of dry and wet age-related macular degeneration (AMD) in patients with diabetes, hypertension and hyperlipidemia, and to analyze the risk factors for AMD.@*Methods@#A population-based cross-sectional epidemiologic study was conducted involving 14,440 individuals. We assessed the prevalence of dry and wet AMD in diabetic and non-diabetic subjects and analyzed the risk factors for AMD.@*Results@#The prevalence of wet AMD in diabetic and non-diabetic patients was 0.3% and 0.5%, respectively, and the prevalence of dry AMD was 17% and 16.4%, respectively. The prevalence of wet AMD in healthy, hypertensive, hyperlipidemic, and hypertensive/hyperlipidemic populations was 0.5%, 0.3%, 0.2%, and 0.7%, respectively. The prevalence of dry AMD in healthy, hypertensive, hyperlipidemic, and hypertensive/hyperlipidemic populations was 16.6%, 16.2%, 15.2%, and 17.2%, respectively. Age, sex, body mass index, and use of hypoglycemic drugs or lowering blood pressure drugs were corrected in the risk factor analysis of AMD. Diabetes, diabetes/hypertension, diabetes/hyperlipidemia, and diabetes/hypertension/hyperlipidemia were analyzed. None of the factors analyzed in the current study increased the risk for the onset of AMD.@*Conclusion@#There was no significant difference in the prevalence of wet and dry AMD among diabetic and non-diabetic subjects. Similarly, there was no significant difference in the prevalence of wet and dry AMD among subjects with hypertension and hyperlipidemia. Diabetes co-existing with hypertension and hyperlipidemia were not shown to be risk factors for the onset of dry AMD.

Comparison of endogenetic microbial community diversity between wild Cordyceps sinensis,artificial C. sinensis and habitat soil / 中国中药杂志

To obtain the difference of the fungal and bacterial community diversity between wild Cordyceps sinensis, artificial C. sinensis and their habitat soil, Illmina Hiseq high-throughput sequencing technology was applied. The results show that Proteobacteria was the dominant bacterial phylum in C. sinensis, Actinobacteria was the dominant bacterial phylum in soil microhabitat, Ophiocordyceps sinensis was the predominant dominant fungus of C. sinensis. The α diversity analysis showed that the fungal diversity of stroma was lower than other parts, and the fungal diversity of wild C. sinensis was lower than that of artificial C. sinensis. The β diversity analysis showed that the fungal and bacterial community diversity of soil microhabitat samples was significantly different from that of C. sinensis. The fungal community diversity was less different between wild and artificial C. sinensis, especially in sclerotia. LEfSe analysis showed a lot of species diversity between wild and artificial C. sinensis. Those different species between wild C. sinensis, artificial C. sinensis and their habitat soil provide ideas for further research on breed and components of C. sinensis.

A 14-year multi-institutional collaborative study of Chinese pelvic floor surgical procedures related to pelvic organ prolapse / 中华医学杂志(英文版)

BACKGROUND@#It has been a global trend that increasing complications related to pelvic floor surgeries have been reported over time. The current study aimed to outline the development of Chinese pelvic floor surgeries related to pelvic organ prolapse (POP) over the past 14 years and investigate the potential influence of enhanced monitoring conducted by the Chinese Association of Urogynecology since 2011.@*METHODS@#A total of 44,594 women with POP who underwent pelvic floor surgeries between October 1, 2004 and September 30, 2018 were included from 22 tertiary academic medical centers. The data were reported voluntarily and obtained from a database. We compared the proportion of each procedure in the 7 years before and 7 years after September 30, 2011. The data were analyzed by performing Z test (one-sided).@*RESULTS@#The number of different procedures during October 1, 2011-September 30, 2018 was more than twice that during October 1, 2004-September 30, 2011. Regarding pelvic floor surgeries related to POP, the rate of synthetic mesh procedures increased from 38.1% (5298/13,906) during October 1, 2004-September 30, 2011 to 46.0% (14,107/30,688) during October 1, 2011-September 30, 2018, whereas the rate of non-mesh procedures decreased from 61.9% (8608/13,906) to 54.0% (16,581/30,688) (Z = 15.53, P < 0.001). Regarding synthetic mesh surgeries related to POP, the rates of transvaginal placement of surgical mesh (TVM) procedures decreased from 94.1% (4983/5298) to 82.2% (11,603/14,107) (Z = 20.79, P < 0.001), but the rate of laparoscopic sacrocolpopexy (LSC) procedures increased from 5.9% (315/5298) to 17.8% (2504/14,107).@*CONCLUSIONS@#The rate of synthetic mesh procedures increased while that of non-mesh procedures decreased significantly. The rate of TVM procedures decreased while the rate of LSC procedures increased significantly.@*TRIAL REGISTRATION NUMBER@#NCT03620565, https://register.clinicaltrials.gov.

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).

Herb-separated moxibustion on navel combined with / 中国针灸

OBJECTIVE@#To compare the clinical therapeutic effect between herb-separated moxibustion on navel combined with @*METHODS@#A total of 66 patients with non-liquefaction semen of dampness and heat diffusing downward were randomized into an observation group (33 cases, 2 cases dropped off) and a control group (33 cases, 2 cases dropped off). In the control group, @*RESULTS@#After treatment, the time of semen liquefaction was shortened (@*CONCLUSION@#Herb-separated moxibustion on navel combined with

Effect of Bushen Tongluo Prescription on Synaptic Plasticity of Hippocampal Neurons of Vascular Dementia Model Rats Based on PI3K/Akt/mTOR Pathway / 中国实验方剂学杂志

Objective:To explore the effect of Bushen Tongluo prescription （BSTLP） on the synaptic plasticity of hippocampal neurons in vascular dementia （VD） model rats and its mechanism. Method:SD male rats of SPF grade were selected. The rat model of VD was established by permanent bilateral ligation of the common carotid artery several times. The model rats were randomly divided into a model group， an insulin-like growth factor-1 （IGF-1， 20 μg·kg^-1） group， high-dose （3 g·kg^-1）， medium-dose （1.5 g·kg^-1）， and low-dose （0.75 g·kg^-1） BSTLP groups. A sham operation group was also set. Drugs were administered to rats by gavage once a day for four weeks. The model group and the sham operation group received the same volume of normal saline. After the last administration， all the rats were detected for spatial learning and memory by the Morris water maze. The apoptosis of hippocampal neurons was detected by terminal deoxynucleotidyl transferase （TdT） dUTP nick-end labeling （TUNEL） assay. The changes in synaptic morphological structure and the number of dendritic spines in hippocampal neurons were detected by Golgi's method. The expression levels of phosphatidylinositol 3-kinase （PI3K）， protein kinase B （Akt）， mammalian target of rapamycin （mTOR）， synaptophysin （SYP）， and amyloid precursor protein （APP） in hippocampal neurons were detected by Western blot. Result:Compared with the sham operation group， the model group showed prolonged escape latency， lengthened swimming distance， dwindled the number of times for the platform crossing after platform removal （<italic>P</italic><0.05）， increased apoptotic cells （<italic>P</italic><0.05）， declining synaptic dendritic spines （<italic>P</italic><0.05）， down-regulated expression levels of PI3K， Akt， mTOR， and SYP proteins， and up-regulated expression level of APP protein in hippocampal neurons （<italic>P</italic><0.05）. Compared with the model group， the BSTLP groups and the IGF-1 group showed shortened escape latency and swimming distance， increased number of times for the platform crossing after platform removal （<italic>P</italic><0.05），declining apoptotic cells （<italic>P</italic><0.05）， up-regulated expression levels of PI3K， Akt， mTOR， and SYP proteins， and down-regulated expression level of APP protein in hippocampal neurons （<italic>P</italic><0.05）. Compared with the IGF-1 group， the high-dose BSTLP group showed no significant difference in the escape latency， swimming distance， the number of times for the platform crossing after platform removal， apoptotic cells， synaptic dendritic spines， and expression levels of PI3K， Akt， mTOR， SYP， and APP proteins in hippocampal neurons. However， the differences were significant in the medium-dose and low-dose BSTLP groups （<italic>P</italic><0.05）. Conclusion:BSTLP can improve the learning and memory of rats with VD. The mechanism is presumedly related to the activation of thePI3K/Akt/mTOR pathway and improvement of synaptic plasticity of hippocampal neurons.