Analysis of Antidepressant Quality Markers of Bupleuri Radix Before and After Vinegar-processing Based on UPLC-Q-TOF-MS and Network Pharmacology / 中国实验方剂学杂志

ObjectiveTo analyze the antidepressant quality markers（Q-Marker） of Bupleuri Radix（BP） before and after vinegar-processing by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）， multivariate statistical analysis and network pharmacology. MethodUPLC-Q-TOF-MS was used to analyze the chemical basis of raw and vinegar-processed products of BP， and principal component analysis（PCA） orthogonal partial least squares-discriminant analysis（OPLS-DA） were used to identify the differential components in BP that changed significantly before and after vinegar-processing， which were regarded as candidate quality markers（Q-Marker）. Then the disease-drug-component-target network related to antidepressant effect of BP was constructed by network pharmacology， and the antidepressant Q-Marker of raw and vinegar-processed products of BP was determined. Rats were randomly divided into blank group， model group， fluoxetine group（2.67 mg·kg-1） and total saponin group（0.72 mg·kg-1）， except the blank group， rats in the other groups were subjected to chronic unpredictable mild stress（CUMS）. Three weeks after the start of modeling， rats in each administration group were given the corresponding dose of drugs once a day for 4 weeks， and rats in the blank and model groups were given normal saline with dose of 10 mL·kg-1. At 1 day before modeling， 21 days and 28 days after administration， body mass weighing， sucrose preference test and open field test were performed on each group . After 28 days of administration， real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） was used to detect the mRNA expression levels of phosphatidylinositol 3-kinase（PI3K）， protein kinase B（Akt）， mammalian target of rapamycin（mTOR）， glycogen synthase kinase-3β（GSK-3β）， forkhead box transcription factor O3a（FoxO3a） and β-catenin in hippocampal tissues of rats in each group， while protein expression levels of PI3K， Akt， mTOR and FoxO3a in hippocampal tissues of rats in each group were detected by Western blot. ResultThere were 19 components in BP showed significant changes before and after vinegar-processing， and 9 components such as saikosaponin A， saikosaponin B1， saikosaponin B2， saikosaponin C and saikosaponin D were identified as potential Q-Marker through S-plot differential marker screening. Combined with the disease-drug-component-target network， saikosaponin A， saikosaponin B1， saikosaponin B2 and saikosaponin D were identified as antidepressant Q-Marker of raw and vinegar-processed products of BP. According to the results of pharmacodynamic tests， after 28 d of administration， compared with the blank group， the body mass， sucrose preference index and open field total score of rats in model group， fluoxetine group and total saponin group decreased significantly（P<0.01）. Compared with the model group， the body mass， sucrose preference index and open field total score in total saponin group increased significantly（P<0.01）. Compared with the blank group， mRNA expression levels of PI3K， Akt， mTOR and β-catenin in hippocampus of rats in the model group decreased significantly（P<0.05）， while mRNA expression levels of GSK-3β and FoxO3a increased significantly（P<0.05）. Compared with the model group， mRNA expression levels of PI3K， Akt， mTOR and β-catenin in hippocampus of rats in the total saponin group were increased significantly（P<0.05）， while mRNA expression levels of GSK-3β and FoxO3a decreased significantly（P<0.05）. Compared with the blank group， the protein expression levels of Akt and mTOR in hippocampus of the model group decreased significantly（P<0.01）， while the protein expression levels of PI3K and FoxO3a increased significantly（P<0.01）. Compared with the model group， the expression level of Akt in hippocampus of the total saponin group increased significantly（P<0.01）， the mTOR expression level was increased but not statistically significant， while the protein expression levels of PI3K and FoxO3a decreased significantly（P<0.01）. ConclusionThe chemical constituents of BP changed greatly after vinegar-processing， and the antidepressant Q-Marker of raw and vinegar-processed products of BP was determined by chemical basis， pharmacodynamics， network pharmacology and signaling pathway， which provided a reference for further research on quality control， pharmacodynamic substance basis and processing mechanism of BP.

Time dependent expression profiling of PTK2B and its relationship with Aβ, Tau and LRP-1 in hippocampus and blood of APPswe/PS1dE9 double-transgenic mouse / 中国应用生理学杂志

Objective: To uncover the time-dependent expression pattern of ptk2b gene and ptk2b-encoded protein, protein tyrosine kinase 2 beta(PTK2B), in the brain tissues of transgenic animal models of Alzheimer's disease (AD) and its relationship with the levels of Aβ1-42, phosphorylation of Tau (p-Tau) and low density lipoprotein receptor-related protein-1(LRP-1) in blood and brain tissues. Methods: In this study, 5-, 10- and 15-month-old APPswe/PS1dE9 double-transgenic mice harboring the genotype of AD confirmed by the gene test were divided into the 5-, 10- and 15-month-old experiment groups, and simultaneously, age-matched C57BL/6J mice were placed into the corresponding control groups, with 8 mice in each group. All mice were subjected to the Morris Water Maze for test of cognitive and behavioral ability. Expression profiles of PTK2B, Aβ1-42, p-Tau/Tau and LRP-1 in the hippocampus or blood of mice were quantified by using the immunohistochemistry staining, Western blot or enzyme-linked immunosorbent assay (ELISA), while the mRNA expression of ptk2b in the hippocampus was quantified by using the real-time quantitative polymerase chain reaction (qRT-PCR). Results: Results of experiment groups demonstrated that as mice aged, the expression levels of PTK2B, ptk2b mRNA, Aβ1-42 and p-Tau/Tau in the hippocampus were increased, and the expression of LRP-1 was decreased gradually. While in the blood, the level of Aβ1-42 was decreased, and the cognitive and behavioral ability was decreased in an age-dependent manner (all P＜ 0.05). However, comparisons among the control groups, only the age-dependent downregulation of LRP-1 were observed in hippocampus(P＜0.05), but other indicators had no significant differences (P＞0.05). Conclusion: In the hippocampus of APP/PS1 double-transgenic mice, the expressions of PTK2B, Aβ1-42 and p-Tau/Tau are upregulated, LRP-1 is downregulated, while cognitive and behavioral ability is decreased, and such changes are presented in a time-dependent manner.

Construction of a nomogram prediction model for pathological complete response (pCR) of ipsilateral supraclavicular lymph node after neoadjuvant chemotherapy for breast cancer with first diagnosis of ipsilateral supraclavicular lymph node metastasis / 中华肿瘤杂志

Objective: To develop a predictive model for pathologic complete response (pCR) of ipsilateral supraclavicular lymph nodes (ISLN) after neoadjuvant chemotherapy for breast cancer and guide the local treatment. Methods: Two hundred and eleven consecutive breast cancer patients with first diagnosis of ipsilateral supraclavicular lymph node metastasis who underwent ipsilateral supraclavicular lymph node dissection and treated in the Breast Department of Henan Cancer Hospital from September 2012 to May 2019 were included. One hundred and forty two cases were divided into the training set while other 69 cases into the validation set. The factors affecting ipsilateral supraclavicular lymph node pCR (ispCR)of breast cancer after neoadjuvant chemotherapy were analyzed by univariate and multivariate logistic regression analyses, and a nomogram prediction model of ispCR was established. Internal and external validation evaluation of the nomogram prediction model were conducted by receiver operating characteristic (ROC) curve analysis and plotting calibration curves. Results: Univariate logistic regression analysis showed that Ki-67 index, number of axillary lymph node metastases, breast pCR, axillary pCR, and ISLN size after neoadjuvant chemotherapy were associated with ispCR of breast cancerafter neoadjuvant chemotherapy (P<0.05). Multivariate logistic regression analysis showed that the number of axillary lymph node metastases (OR=5.035, 95%CI: 1.722-14.721, P=0.003), breast pCR (OR=4.662, 95%CI: 1.456-14.922, P=0.010) and ISLN size after neoadjuvant chemotherapy (OR=4.231, 95%CI: 1.194-14.985, P=0.025) were independent predictors of ispCR of breast cancer after neoadjuvant chemotherapy. A nomogram prediction model of ispCR of breast cancer after neoadjuvant chemotherapy was constructed using five factors: number of axillary lymph node metastases, Ki-67 index, breast pCR, axillary pCR and size of ISLN after neoadjuvant chemotherapy. The areas under the ROC curve for the nomogram prediction model in the training and validation sets were 0.855 and 0.838, respectively, and the difference was not statistically significant (P=0.755). The 3-year disease-free survival rates of patients in the ispCR and non-ispCR groups after neoadjuvant chemotherapy were 64.3% and 54.8%, respectively, with statistically significant differences (P=0.024), the 3-year overall survival rates were 83.8% and 70.2%, respectively, without statistically significant difference (P=0.087). Conclusions: Disease free survival is significantly improved in breast cancer patients with ispCR after neoadjuvant chemotherapy. The constructed nomogram prediction model of ispCR of breast cancer patients after neoadjuvant chemotherapy is well fitted. Application of this prediction model can assist the development of local management strategies for the ipsilateral supraclavicular region after neoadjuvant chemotherapy and predict the long-term prognosis of breast cancer patients.

Effects of Huaiqihuang Granules on airway inflammation in bronchiolitis / 中国基层医药

Objective:To investigate the effects of Huaiqihuang Granule on airway inflammation and wheezing reattack in bronchiolitis. Methods:A total of 120 patients with bronchiolitis presenting airway inflammation and wheezing reattack who received treatment in Zaozhuang Municipal Hospital and Yicheng Hospital of Traditional Chinese Medicine between January 2018 and October 2019 were included in this study. These patients randomly underwent either conventional treatment (control group, n = 60) or conventional treatment + Huaiqihuang Granule treatment (experimental group, n = 60). They received pulmonary function examinations and laboratory tests for evaluating serum and urinary inflammatory factors at admission and 2 months after discharge. They were followed up by telephone 3 months and 1 year after onset. Results:The ratio of time to reach the peak tidal expiratory flow over total expiratory time (TPTEF/TE) and the volume to peak tidal expiratory flow to total expiratory volume (VPTEF/VE) were significantly higher in the experimental group compared with those in the control group ( t = 3.13, 3.60, all P < 0.01). The ratio of tidal peak flow to tidal expiratory flow when 25% of tidal volume remains in the lungs (PF/TEF25) and functional residual capacity/kg (FRCp/kg) significantly decreased in the experimental group compared with those in the control group ( t = 3.88, 3.74, all P < 0.01). Interleukin-4 level and the ratio of interleukin-4/γ-interferon levels were significantly lower in the experimental group than in the control group ( t = 5.70, 8.93, all P < 0.01). Gamma-interferon level was significantly higher in the experimental group than in the control group ( t = 3.85, P < 0.01). There was no significant difference in urinary leukotriene E4 level post-treatment between the two groups ( t = 1.18, P > 0.05). The number of patients who had a wheezing attack again within 3 months post-treatment and the number of patients who had ≥3 wheezing attacks were significantly lower in the experimental group compared with those in the control group ( χ2 = 5.18, 6.98, P < 0.01 or 0.05). Conclusion:Huaiqihuang granule can effectively regulate the balance of the Th 1/Th 2 ratio, inhibit airway inflammation in bronchiolitis, improve pulmonary function, and reduce the number of wheezing reattacks.

Rethinking the marketing strategy of anti-tumor drugs by single-arm trials supported / 中华肿瘤杂志

Single-arm trial refers to a clinical trial design that does not set up parallel control group, adopts open design, and does not involve randomization and blind method. These features, on the one hand, speed up the process of clinical trials, significantly shorten the time to market and meet the needs of patients with advanced malignancies, but also lead to the uncertainty of single-arm clinical trials themselves. Recently, the US Food and Drug Administration held a meeting of the oncologic drug advisory committee to discuss six tumor indications that have been accelerated approved, which once again triggered the discussion of single-arm trials. The basis of accelerated approval by single-arm trial is actually a compromise on the level of evidence-based medical evidence requirements after assessing the benefit risk. Therefore, the sponsor should strictly grasp the applicable conditions of single-arm trial in anti-tumor drugs and conduct single-arm trial scientifically. Post-marketing clinical trial should be implement as early as possible to ensure the benefit of patients. Based on the characteristics of single-arm trial, combined with two guidance relevant to single-arm trial issued by National Medical Products Administration recently, this article is supposed to propose and summarize the strategy of single-arm trial supporting the marketing of anti-tumor drugs.

Application and thinking of cohort study in clinical research of acupuncture and moxibustion / 中国针灸

Cohort study has been greatly considered and widely used in clinical research of traditional Chinese medicine in China, but it is seldom applied in the field of acupuncture and moxibustion. This paper introduces the development background, basic concepts, advantages and limitations of cohort study, analyzes the existing problems in the evaluation of acupuncture and moxibustion curative effect and development status of cohort study in the cycle of acupuncture and moxibustion, explores the feasibility and value of such method in clinical research of acupuncture and moxibustion and proposes the methodological suggestions on rigorous design, control of selective bias, control of cohort migration and reduction of loss to follow

Progress of circulating RNA in liquid biopsy of cervical cancer / 中华检验医学杂志

Cervical cancer poses a major threat to public health worldwide, early diagnosis of cervical cancer can improve the survival rate of patients. The detection rate of the existing cervical cancer screening methods is not very stable, and there is no reliable non-invasive index to predict the recurrence, metastasis and prognosis of cervical cancer. We searched literaruture for cervical cancer-related diagnostic and prognostic indicators and included 20 related literature, confirming that liquid biopsy is expected to replace and supplement the existing methods of screening and testing. Circulating nucleotides are an important part of liquid bioassays, including circulating cell-free DNA (cfDNA) and circulating cell-free RNA (cfRNA), among which cfRNA is a potentially rich source of tumor biomarkers, especially in the early diagnosis of cervical cancer. It has unique specificity and great potential value in the early diagnosis.

Analysis of research development of endemic fluorosis in China based on bibliometrics and mapping knowledge domains / 中华地方病学杂志

Objective:To review the research progress of endemic fluorosis in China in the past decade, and to provide references for prevention and control of endemic fluorosis.Methods:Using Wanfang Data Knowledge Service Platform as the information source, research papers in the field of endemic fluorosis from 2008 to 2017 were retrieved, and the publication status, core authors, cooperation status, and research hotspots were analyzed.Results:A total of 2 068 papers were retrieved, with 297 and 298 articles published in 2009 and 2010, while 94 and 103 articles were published in 2016 and 2017, respectively. There were 8 420 authors in 2 068 articles, with an average of 4 authors per article. According to the statistics of the first authors, the number of papers published by the most productive authors was 21. There were 59 first authors who had published more than 4 papers, they had published 371 papers, accounting for 17.94% of the total number of papers. Analysis of the author's cooperation showed that the research teams with larger scale and closer cooperation were from Harbin Medical University, Guizhou Provincial Center for Disease Control and Prevention, Guizhou Medical University, Shandong Institute for Prevention and Control of Endemic Disease, Shaanxi Provincial Institute for Endemic Disease Prevention and Control, Chongqing Center for Disease Control and Prevention, Hulunbuir City Institute for Endemic Disease Prevention and Control of Inner Mongolia Autonomous Region, Qinghai Institute for Endemic Disease Prevention and Control. The hotspots and themes of the study focused on epidemiological investigation of endemic fluorosis, health education, pathogenesis and other related research of endemic fluorosis.Conclusion:In Chinese periodicals, the number of papers published on endemic fluorosis has been reduced, the construction of talent team needs to be strengthened, and the research hotspots and themes are changing steadily.

PTK2B affects the levels of Aβ in blood and brain and behavioral functions via targeting LRP-1 transporter in Aβ-induced cognitive dysfunction mice / 生理学报

The aim of the present study was to explore the correlation between ptk2b/PTK2B (protein tyrosine kinase 2 beta, a ptk2b-encoded protein) and the level of low density lipoprotein receptor-related protein-1 (LRP-1), as well as to uncover the relationship between the changes in beta amyloid protein (Aβ) levels in blood and brain and the expression of ptk2b in Aβ-induced cognitive dysfunction mice. A total of 64 3-month-old C57BL/6J mice were divided randomly into the experimental group and control group. All mice underwent the intracerebroventricular (i.c.v.) intubation. Mice in the experimental group received the i.c.v. infusion of oligomeric Aβ

Development and validation of a nomogram for predicting survival of breast cancer patients with ipsilateral supraclavicular lymph node metastasis / 中华医学杂志(英文版)

BACKGROUND@#Breast cancer patients with ipsilateral supraclavicular lymph node metastasis (ISLNM) but without distant metastasis are considered to have a poor prognosis. This study aimed to develop a nomogram to predict the overall survival (OS) of breast cancer patients with ISLNM but without distant metastasis.@*METHODS@#Medical records of breast cancer patients who received surgical treatment at the Affiliated Cancer Hospital of Zhengzhou University, Jiyuan People's Hospital and Huaxian People's Hospital between December 21, 2012 and June 30, 2020 were reviewed retrospectively. Overall, 345 patients with pathologically confirmed ISLNM and without evidence of distant metastasis were identified. They were further randomized 2:1 and divided into training (n = 231) and validation (n = 114) cohorts. A nomogram to predict the probability of OS was constructed based on clinicopathologic variables identified by the univariable and multivariable analyses. The predictive accuracy and discriminative ability were measured by calibration plots, concordance index (C-index), and risk group stratification.@*RESULTS@#Univariable analysis showed that estrogen receptor-positive (ER+), progesterone receptor-positive (PR+), human epidermal growth factor receptor 2-positive (HER2+) with Herceptin treatment, and a low axillary lymph node ratio (ALNR) were prognostic factors for better OS. PR+, HER2+ with Herceptin treatment, and a low ALNR remained independent prognostic factors for better OS on multivariable analysis. These variables were incorporated into a nomogram to predict the 1-, 3-, and 5-year OS of breast cancer patients with ISLNM. The C-indexes of the nomogram were 0.737 (95% confidence interval [CI]: 0.660-0.813) and 0.759 (95% CI: 0.636-0.881) for the training and the validation cohorts, respectively. The calibration plots presented excellent agreement between the nomogram prediction and actual observation for 3 and 5 years, but not 1 year, OS in both the cohorts. The nomogram was also able to stratify patients into different risk groups.@*CONCLUSIONS@#In this study, we established and validated a novel nomogram for predicting survival of patients with ISLNM. This nomogram may, to some extent, allow clinicians to more accurately estimate prognosis and to make personalized therapeutic decisions for individual patients with ISLNM.

Advances in researches on neoadjuvant therapy for resectable colorectal liver metastasis / 中华胃肠外科杂志

Surgery is recognized as the core treatment for colorectal liver metastasis (CRLM), while its recurrence rate remains relatively high, even for resectable CRLM. This hints that the efficacy of treatment involves not only technological factors of surgery, but also biological behavior of tumor. For resectable CRLM, neoadjuvant therapy is beneficial to eliminate the micro-metastasis, reduce postoperative recurrence rate, screen tumor biological behavior and improve prognosis. However, questions about which kind of CRLM patients fits for neoadjuvant therapy and what regimen should be used are still debatable. This paper reviews stratified management of resectable CRLM, choice of neoadjuvant regimen, especially the application value of targeted therapy, based on the latest guidelines and studies.

Effects of Mechanical Stimulation on Polarity of Macrophages / 医用生物力学

Objective To explore the effect of mechanical stimulation on polarity of macrophages. Methods RAW264.7 cells were stimulated with tensile stretch at various amplitude and time, then cell viability was assessed with cell count kit-8 (CCK-8) for determining the stimulation parameters. RAW264.7 cells were induced to M1 type, then tensile stretch at 10% amplitude and 2 Hz was applied to M1 cells. CCK-8 and flow cytometry were used to detect the effects of tensile stretch on cell activity and apoptosis. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the effect of tensile stretch on M1 type macrophage related gene expression. Results After stimulation for 3 hours, tensile stretch at 15% or 20% amplitude and 2 Hz significantly inhibited cell viability (P0.05). Tensile stretch at 10% amplitude and 2 Hz neither inhibited viability nor cause apoptosis of M1 type macrophages. The expression of inflammation-related genes including interleukin-1β(IL-1β) and tumor necrosis factor-α (TNF-α) of M1 type macrophages was significantly down-regulated with tensile stretch at 10% amplitude and 2 Hz (P＜0.05). Conclusions Mechanical stimulation at 10% amplitude and 2 Hz can inhibit M1 type macrophages and promote the polarization from M1 to M2. Mechanical stimulation may become a method for treating inflammation-related diseases.

Analysis of clinical efficacy of C expanded half lamina excision combined with unilateral open-door laminoplasty for multiple segmental cervical spinal cord compression syndrome / 中国骨伤

OBJECTIVE@#To explore the clinical efficacy of C expanded half lamina excision combined with unilateral open door laminoplasty for multiple segmental cervical spinal cord compression syndrome.@*METHODS@#The clinical data of 58 patients with multiple segmental cervical spinal cord compression syndrome underwent surgical treatment between September 2014 and May 2018 were retrospectively analyzed. There were 34 males and 24 females with a mean age of 64.4 years old (ranged from 46 to 78 years old). Among them, 28 cases received the surgery of C expanded half lamina excision combined with C-C unilateral open-door laminoplasty (improvedgroup), and 30 cases received a single C-C unilateral open-door laminoplasty (traditional group). Operation time, intraoperative blood loss, complications including C nerve root palsy and axial symptoms were compared between two groups. To evaluate the situation of the imaging indicators by measuring the space available for the spinal cord through cross sectional MRI of cervical spine at the narrowest segment of C (including intervertebral disc levels of C). Pre- and post-operative Japanese Orthopedic Association(JOA) score, Neck Disability Index(NDI) score, and improvement rate of neurological function, were recorded and analyzed between the two groups.@*RESULTS@#All the patients were followed up for 12 to 18 months with an average of(14.5±1.8) months for improved group and (14.5±1.9) months for traditional group, and no significant difference was found between the two groups (>0.05). There was no significant difference in intraoperative blood loss and C nerve root palsy between the two groups (>0.05). The operation time (119±10) min vs (126±12) min and axial symptoms 7.1%(2/28) vs 26.6%(8/30) was significant difference between the two groups (0.05).@*CONCLUSION@#C expanded half lamina excision combined with unilateral open-door laminoplasty is an effective method to treat multiple segmental cervical spinal cord compression syndrome, for it can not only fully relieved spinal cord compression, but also achievedgood effect in preventing complications such as axial symptoms by reducing stripping of muscles from C2 spinous process.

Research progress and perspective in metabolism and metabolomics of psoriasis / 中华医学杂志(英文版)

Psoriasis is considered a systemic disease associated with metabolic abnormalities, and it is important to understand the mechanisms by which metabolism affects pathophysiological processes both holistically and systematically. Metabolites are closely related to disease phenotypes, especially in systemic diseases under multifactorial modulation. The emergence of metabolomics has provided information regarding metabolite changes in lesions and circulation and deepened our understanding of the association between metabolic reprogramming and psoriasis. Metabolomics has great potential for the development of effective biomarkers for clinical diagnosis, therapeutic monitoring, prediction of the efficacy of psoriasis management, and further discovery of new metabolism-based therapeutic targets.

Phylogenetic characteristics, virulence and antibiotic resistance of Aeromonas caviae isolated from foodborne and environmental samples / 中华微生物学和免疫学杂志

Objective:To identify 49 Aeromonas caviae strains isolated form foodborne and environmental samples and analyze their virulence and antibiotic resistance. Methods:All strains were identified by VITEK and API 20NE. Two housekeeping genes, gryB and rpoD, were amplified by PCR for phylogenetic analysis. Virulence genes including act, alt, ast, lip, ahp, aerA, hlyA, ompA1 and fla were detected by PCR. In vitro antimicrobial susceptibility of these strains was tested with AST-GN16 kit. Results:Fifty-four Aeromonas caviae/ Aeromonas hydrophila strains were identified by biochemical tests. Phylogenetic analysis revealed that there were 49 Aeromonas caviae strains, four Aeromonas hydrophila strains and one Aeromonas taiwanensis strain. The positive rates of alt, lip, ompA1, fla, act, aerA and hlyA genes were 100.00%, 100.00%, 79.59%, 14.29%, 2.04%, 2.04% and 2.04%, respectively. None of the isolates carried ast or ahp gene. A total of four virulence gene combination patterns were detected, and the predominant pattern was alt/ lip/ ompA1 (32/49). Antibiotic resistance rates of the Aeromonas caviae strains to ampicillin, cefazolin, cefoxitin, amoxicillin/clavulanic acid, ceftriaxone, trimethoprim/sulfamet hoxoazole and aztreonam were 79.59%, 14.29%, 10.20%, 6.12%, 4.08%, 4.08% and 2.04%, respectively. All strains were susceptible to piparacillin/tazobactam, imipenem, amikacin, gentamicin, levofloxacin, tigacycline and nitrofurantoin. Two multidrug-resistant strains were detected. Conclusions:Aeromonas caviae/ Aeromonas hydrophila can be effectively identified by the housekeeping genes gyrB and rpoD, and the closely related Aeromonas caviae and Aeromonas taiwanensis strains can be identified by rpoD. All Aeromonas caviae strains carried two or more virulence genes and one strain isolated from environment was positive for seven virulence genes. Aeromonas caviae strains were generally resistant to penicillin, which was mainly relate to the production of β-lactamase. No strain was resistant to carbapenems, aminoglycosides, fluoroquinolones, tetracyclines or furans. Multidrug-resistant strains were observed in food and drinking water.

Origin and relationship of -well points and Shixuan (EX-UE 11) / 中国针灸

Both the twelve -well points and Shixuan (EX-UE 11) are the commonly used first-aid points. These two kinds of acupoints are located closely and similar in function, hence, they are often confused in application. In order to explore the origin of their location and theory as well as their relationship, the relevant data were retrieved. It has been found that the relationship between -well points and Shixuan (EX-UE 11) is traced at the earliest time to (). It is believed that the -well points refer to the starting points or the ending points of the twelve regular meridians and Shixuan (EX-UE 11) are located at the crossing sites of - related meridians of the regular meridians. These two kinds of acupoints are interconnected, share the same source and are also different from each other. Qiduan (EX-LE 12) is also named as foot-Shixuan. Shixuan (EX-UE 11) and Qiduan (EX-LE 12) can be regarded as the same category, just like -well points. In clinical practice, the -well points are generally selected in treatment of internal diseases, local diseases and those on the running course of meridians. They can be used separately in treatment. Shixuan (EX-UE 11) is the first option, or combined with Qiduan (EX-LE 12) in the emergent treatment of tense syndrome and syncope. The -well points and Shixuan (EX-UE 11) are different even though sharing the same origin. They are mutually benefited and supplemented with each other in clinical practice.

Long-term oncological outcomes of laparoscopic versus abdominal surgery in stage Ⅰa1 （LVSI +）-Ⅰb1 cervical cancer patients with different tumor size: a big database in China / 中华妇产科杂志

Objective:To compare the long-term oncological outcomes between laparoscopic and abdominal surgery in stage Ⅰa1 （lymph-vascular space invasion-positive, LVSI +）- Ⅰb1 cervical cancer patients with different tumor sizes. Methods:Based on the Big Database of Clinical Diagnosis and Treatment of Cervical Cancer in China (1538 project database), patients with stage Ⅰa1 （LVSI +）-Ⅰb1 cervical cancer who treated by laparoscopic or abdominal surgery were included. The 5-year overall survival (OS) and 5-year disease-free survival (DFS) between the two surgical approaches were compared under 1∶1 propensity score matching (PSM) in different tumor diameter stratification. Results:(1) A total of 4 891 patients with stage Ⅰa1 （LVSI +）-Ⅰb1 cervical cancer who underwent laparoscopy or laparotomy from January 1, 2009 to December 31, 2016 were included in the 1538 project database. Among them, 1 926 cases in the laparoscopic group and 2 965 cases in the abdominal group. There were no difference in 5-year OS and 5-year DFS between the two groups before matching. Cox multivariate analysis suggested that laparoscopic surgery was associated with lower 5-year DFS ( HR=1.367, 95% CI: 1.105-1.690, P=0.004). After 1∶1 PSM matching, 1 864 patients were included in each group, and there was no difference in 5-year OS between the two groups （94.1% vs 95.4%, P=0.151）. While, the inferior 5-year DFS was observed in the laparoscopic group (89.0% vs 92.3%, P=0.004). And the laparoscopic surgery was associated with lower 5-year DFS ( HR=1.420, 95% CI: 1.109-1.818, P=0.006). (2) In stratification analysis of different tumor sizes, and there were no difference in 5-year OS and 5-year DFS between the laparoscopic group and abdominal group in tumor size ≤1 cm, >1-2 cm and >2-3 cm stratification (all P>0.05). Cox multivariate analysis showed that laparoscopic surgery were not related to 5-year OS and 5-year DFS ( P>0.05). In the stratification of tumor size >3-4 cm, there was no difference in 5-year OS between the two groups ( P>0.05). The 5-year DFS in the laparoscopic group was worse than that in the abdominal group (75.7% vs 85.8%, P=0.025). Cox multivariate analysis suggested that laparoscopic surgery was associated with lower 5-year DFS ( HR=1.705, 95% CI: 1.088-2.674, P=0.020). Conclusions:For patients with stage Ⅰa1 （LVSI +）-Ⅰb1 cervical cancer, laparoscopic surgery is associated with lower 5-year DFS, and the adverse effect of laparoscopic surgery on oncology prognosis is mainly reflected in patients with tumor size >3-4 cm. For patients with tumor sizes ≤1 cm, >1-2 cm and >2-3 cm, there are no difference in oncological prognosis between the two surgical approaches.

Exploration into the simplex reinforcing-reducing manipulation of acupuncture / 中国针灸

Four controversial types of simplex reinforcing-reducing manipulation of acupuncture and their possible meanings were summarized to explore several key elements of reinforcing-reducing manipulation of acupuncture, in addition, the simplex reinforcing-reducing manipulation of acupuncture was classified by single factor. It is concluded that the definition of simplex reinforcing-reducing manipulation of acupuncture should try not to include other non-manipulative elements. According to single factor, it can be divided into: needle-oriented reinforcing-reducing manipulation, twisting reinforcing-reducing manipulation, lifting and interpolating reinforcing-reducing manipulation, fast and slow reinforcing-reducing manipulation, breathing reinforcing-reducing manipulation, opening and closing reinforcing-reducing manipulation. In addition, after considering the effect and principle of number reinforcing-reducing manipulation, it can be considered.

Effect of added halide ions and pH on the solubility of nebivolol hydrochloride and the evaluation of selected, discriminating dissolution media / 药学学报

The solubility of nebivolol hydrochloride was determined in acidic aqueous media in the absence and presence of different concentration of NaCl, NaBr, or NaI at 37 ℃ in order to facilitate proper selection of dissolution media that have adequate discriminating power for enhancing the likelihood of a generic drug product to successfully pass in-vivo bioequivalence test. In the range of pH 5.0 to pH 1.0, the solubility of nebivolol hydrochloride decreased with the decrease in the pH of aqueous solution, and the solubility of nebivolol hydrochloride further decreased with the increase in the concentration of added sodium chloride. The solubility decrease of a few weakly basic drug molecules in acidic media and in higher concentration of added chloride was published previously by other researchers, and the observed decrease in the solubility in the presence of higher chloride concentration was interpreted in terms of common-ion effect. However, the results in this paper showed that the solubility of nebivolol hydrochloride also decreased when sodium chloride was replaced with sodium bromide or iodide. The approach described in this paper (i.e. substituting sodium chloride with sodium bromide or iodide) provides an effective method to verify whether common-ion effect is the true (or at least the sole) driving force behind the observed decrease in the solubility of nebivolol hydrochloride in the presence of sodium chloride. The solubility decrease reported in this paper can be interpreted in terms of salting-out effect of sodium chloride, bromide, and iodide. For hydrochloride salt of a weakly basic drug molecule like nebivolol hydrochloride, its solubility in an acidic dissolution medium can be purposely decreased to the lower end of sink condition by adding sodium chloride to make the resulting medium more discriminating. As shown in this paper, a medium at pH 1.2 with added sodium chloride is discriminating and this medium is shown to be bio-relevant to the in-vivo data collected under fasting condition (in-vivo study protocol was approved by Institutional Review Board).

Trend in proportion and clinicopathological characteristics of young women with stage Ⅰa2 to Ⅱa2 cervical cancer / 中华妇产科杂志

Objective@#To analyze the 13 years trend in proportion, risks factors and clinicopathological characteristics of young women with stage Ⅰa2 to Ⅱa2 cervical cancer by using multi-center data of cervical cancer in China.@*Methods@#The clinicopathological data of 46 313 patients with cervical cancer treated from 37 hospitals in China were obtained from January 2004 to December 2016. Using clinical and pathologic data, each patient's stage was reclassified by the 2018 International Federation of Gynecology and Obstetrics (FIGO) staging system. A total of 19 041 patients were selected according to the following criteria: FIGO stage Ⅰa2 to Ⅱa2, underwent type B or C radical hysterectomy and pelvic lymphadenectomy. All the patients were divided into two groups: the study group of 1 888 patients aged 35 years or younger and the control group of 17 153 patients aged over 35 years. The 13 years trend in proportion of young women with stage Ⅰa2 to Ⅱa2 cervical cancer, risks factors and clinicopathological characteristics of two groups were retrospectively analyzed.@*Results@#(1) The total number of hospitalized patients with stage Ⅰa2 to Ⅱa2 cervical cancer increased annually. However, a downward trend of patients aged 35 years or younger was observed (P<0.01) . The constituent ratio of patients aged 35 years or younger was significantly greater during 2004—2010 than that during 2011—2016 [12.6% (820/6 484) and 8.5% (1 068/12 557) , respectively; χ2=82.101, P<0.01]. (2) Compared with patients aged over 35 years, patients aged 35 years or younger had an earlier age at menarche, a later age at marriage, lesser gravida and parity (all P<0.01). The positive rate of high-risk HPV infection was not statistically different between two groups (all P>0.05). (3) The proportions of stage Ⅰ, exophytic type and non-squamous histological type in patients aged 35 years or younger were clearly higher than those in patients aged over 35 years (83.4% vs 68.5%, P<0.01; 63.2% vs 56.2%, P<0.01; 13.9% vs 12.0%, P<0.05, respectively). Whereas the poor differentiation ratios of the two groups had no statistical significance (P>0.05). (4) As for the postoperative pathological risk factors, the rate of surgical margin involvement in patients aged 35 years or younger was lower than that aged over 35 years (1.1% vs 1.8%, P<0.05), and the rate of depth of stromal invasion >1/2 in patients aged 35 years or younger was lower than that in patients aged over 35 years (40.1% vs 50.9%, P<0.01). In addition, there were no significant difference in parametrial margin involvement, tumor size and lymph vascular space invasion between two groups (all P>0.05).@*Conclusions@#The trend in proportion among hospitalized patients for stage Ⅰa2 to Ⅱa2 cervical cancer in young women is decreasing yearly. Compared with cervical cancer in middle-aged and elderly women, cervical cancer in young women have an earlier age at menarche, a higher proportion of stage Ⅰ patients and non-squamous histological type. In terms of the postoperative pathological risk factors, the rate of surgical margin involvement and depth of stromal invasion >1/2 in young women with cervical cancer are lower than in middle-aged and elderly women.