Precise Post-Synthetic Modification of Heterometal-Organic Capsules for Selectively Encapsulating Tetrahedral Anions.

Post-synthetic modification plays a crucial role in precisely adjusting the structure and functions of advanced materials. Herein, we report the self-assembly of a tubular heterometallic Pd3Cu6L16 capsule that incorporates Pd(II) and CuL1 metalloligands. This capsule undergoes further modification with two tridentate anionic ligands (L2) to afford a bicapped Pd3Cu6L16L22 capsule with an Edshammer polyhedral structure. By employing transition metal ions, acid, and oxidation agents, the bicapped capsule can be converted into an uncapped one. This uncapped form can then revert back to the bicapped structure on the addition of Br- ions and a base. Interestingly, introducing Ag+ ions leads to the removal of one L2 ligand from the bicapped capsule, yielding a mono-capped Pd3Cu6L16L2 structure. Furthermore, the size of the anions critically influences the precise control over the post-synthetic modifications of the capsules. It was demonstrated that these capsules selectively encapsulate tetrahedral anions, offering a novel approach for the design of intelligent molecular delivery systems.

Self-Assembly of Two Tubular Metalloligand-Based Palladium-Organic Cages as Hosts for Polycyclic Aromatic Hydrocarbons.

Herein we report two tubular metal-organic cages (MOCs), synthesized by the self-assembly of bidentate metalloligands with different lengths and PdII. These two MOCs feature Pd4L8-type square tubular and Pd3L6-type triangular cage structures, respectively. Both MOCs have been fully characterized by NMR spectroscopy, mass spectrometry, and theoretical calculation. Both cages can be employed for encapsulating polycyclic aromatic hydrocarbons and show high binding affinity toward coronene.

Preliminary experience of gasless transoral vestibular robotic thyroidectomy / 中华耳鼻咽喉头颈外科杂志

Objective: To explore the feasibility and safety of the gasless transoral vestibular robotic thyroidectomy using skin suspension. Methods: The clinical data of 20 patients underwent gasless transoral vestibular robotic thyroidectomy in the Department of Otorhinolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University from February 2022 to May 2022 were retrospectively analyzed. Among them, 18 were females and 2 were males, aged (38.7±8.0) years old. The intraoperative blood loss, operation time, postoperative hospital stay, postoperative drainage volume, postoperative pain visual analogue scale (VAS) score, postoperative swallowing function swallowing impairment score-6 (SIS-6), postoperative aesthetic VAS score, postoperative voice handicap index-10 (VHI-10) voice quality, postoperative pathology and complications were recorded. SPSS 25.0 was used for statistical analysis of the data. Results: The operations were successfully completed without conversion to open surgery in all patients. Pathological examination showed papillary thyroid carcinoma in 18 cases, retrosternal nodular goiter in 1 case, and cystic change in goiter in 1 case. The operative time for thyroid cancer was 161.50 (152.75, 182.50) min [M (P25, P75), the same below] and the average operative time for benign thyroid diseases was 166.50 minutes. The intraoperative blood loss 25.00 (21.25, 30.00) ml. In 18 cases of thyroid cancer, the mean diameter of the tumors was (7.22±2.02) mm, and lymph nodes (6.56±2.14) were dissected in the central region, with a lymph node metastasis rate of 61.11%. The postoperative pain VAS score was 3.00 (2.25, 4.00) points at 24 hours, the mean postoperative drainage volume was (118.35±24.32) ml, the postoperative hospital stay was 3.00 (3.00, 3.75) days, the postoperative SIS-6 score was (4.90±1.58) points at 3 months, and the postoperative VHI-10 score was 7.50 (2.00, 11.00) points at 3 months. Seven patients had mild mandibular numbness, 10 patients had mild cervical numbness, and 3 patients had temporary hypothyroidism three months after surgery and 1 patient had skin flap burn, but recovered one month after surgery. All patients were satisfied with the postoperative aesthetic effects, and the postoperative aesthetic VAS score was 10.00 (10.00, 10.00). Conclusion: Gasless transoral vestibular robotic thyroidectomy using skin suspension is a safe and feasible option with good postoperative aesthetic effect, which can provide a new treatment option for some selected patients with thyroid tumors.

Analgesic effect of auricular point acupressure for acute pain in patients with dementia: study protocol for a randomized controlled trial.

BACKGROUND: Common and frequent as acute pain is, it is often underestimated and undertreated in older people with dementia in nursing homes and inadequate pain management remains an issue. METHODS: The study is designed to be a randomized, sham-controlled trial and is underway in nursing homes located in China. A total of 206 dementia patients are being recruited from nursing homes in Yinchuan, China. They are randomly allocated to an intervention or a controlled group in a 1:1 ratio. The intervention group will be treated with true APP therapy, while the other group will receive APP at sham point stimulation therapy. The patients will be assessed at baseline (T0), at 5 min during performing the intervention (T1), and at 5 min after completion of the intervention (T2). The primary outcome is the level of pain relief at T1 and T2. Physiological parameters, side effects and additional use of analgesics during the procedure, satisfaction from caregivers, and acceptance of patients are evaluated as secondary outcomes. DISCUSSION: The results of this study are expected to verify the analgesic effect of APP for acute pain in patients with mild dementia in nursing homes. It has the potential to prompt APP therapy to be implemented widely in dementia patients with acute pain in nursing homes. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100047932 . Registered on 27 June 2021. Currently, patient recruitment is ongoing. Recruitment is expected to take place from December 2020 to December 2021.

Self-Assembly of a Pd4Cu8L8 Cage for Epoxidation of Styrene and Its Derivatives.

Herein we report a discrete heterometallic Pd4Cu8L8 cage with a tubular structure, which was synthesized by the assembly of copper metalloligands and PdII ions in a stepwise manner. The Pd4Cu8L8 cage has been unequivocally characterized by single-crystal X-ray diffraction, electrospray ionization-mass spectroscopy, and energy dispersive spectroscopy. The cage showed excellent catalytic activity in the epoxidation of styrene and its derivatives under conditions without using additional solvent, providing potential material for catalyzing the oxidation reactions.

SoySNP618K array: A high-resolution single nucleotide polymorphism platform as a valuable genomic resource for soybean genetics and breeding.

Innovations in genomics have enabled the development of low-cost, high-resolution, single nucleotide polymorphism (SNP) genotyping arrays that accelerate breeding progress and support basic research in crop science. Here, we developed and validated the SoySNP618K array (618,888 SNPs) for the important crop soybean. The SNPs were selected from whole-genome resequencing data containing 2,214 diverse soybean accessions; 29.34% of the SNPs mapped to genic regions representing 86.85% of the 56,044 annotated high-confidence genes. Identity-by-state analyses of 318 soybeans revealed 17 redundant accessions, highlighting the potential of the SoySNP618K array in supporting gene bank management. The patterns of population stratification and genomic regions enriched through domestication were highly consistent with previous findings based on resequencing data, suggesting that the ascertainment bias in the SoySNP618K array was largely compensated for. Genome-wide association mapping in combination with reported quantitative trait loci enabled fine-mapping of genes known to influence flowering time, E2 and GmPRR3b, and of a new candidate gene, GmVIP5. Moreover, genomic prediction of flowering and maturity time in 502 recombinant inbred lines was highly accurate (>0.65). Thus, the SoySNP618K array is a valuable genomic tool that can be used to address many questions in applied breeding, germplasm management, and basic crop research.

Effect of Qinggan Zishen Prescription on Metabolic Disorder in Obesity-related Hypertension and Its Mechanism Based on Network Pharmacology / 中国实验方剂学杂志

ObjectiveTo explore the effect of Qinggan Zishen prescription on metabolic disorders in obesity-related hypertension （OBH） patients and analyze the potential pharmacological mechanism based on network pharmacology. MethodA total of 85 eligible OBH patients who were treated in the outpatient or wards of Jiangsu Province Hospital of Chinese medicine from September 2018 to January 2020 were selected and randomized into the observation group （45 cases） and control group （40 cases）. All patients were treated with western medicine during a four-week introduction period， and then the observation group was treated with Qinggan Zishen prescription on the basis of western medicine. The study lasted 6 months， and indicators， such as triglycerides （TG）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， glycosylated hemoglobin （HbA1c）， fasting blood glucose （FBG）， fasting insulin （FINS）， waist circumference （W）， hip circumference （H） were detected and homeostasis model assessment of insulin resistance （HOMA-IR），body mass index （BMI）， waist-hip ratio （WHR） were calculated before and after intervention. At the same time， the regulation network of the Qinggan Zishen prescription was visualized and the protein-protein interaction （PPI） network was constructed. The core targets of the network were obtained for Gene Ontology （GO） term enrichment and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis. ResultAfter intervention for 6 months， the levels of W， H， WHR， FINS， and HOMA-IR in the observation group were reduced as compared with those in the control group （P<0.05， P<0.01）. According to network pharmacology， the main components of Qinggan Zishen prescription in treating OBH were luteolin， quercetin， and berberine and the key targets were amyloid precursor protein （APP）， vascular endothelial growth factor A （VEGFA）， and estrogen receptor 1 （ESR1）. Moreover， the key biological pathway was advanced glycation end product （AGE）/advanced glycation end product receptor （RAGE） signaling pathway. ConclusionQinggan Zishen prescription can improve the metabolic disorder of OBH patients through multiple components， multiple targets， and multiple pathways， which provides new mindset for follow-up studies.

Transoral robotic nasopharyngectomy for local recurrent nasopharyngeal carcinoma / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the safety, efficacy, locally control and survival results of transoral Da Vinci robotic surgery for salvage treatment of locally recurrent nasopharyngeal carcinoma. Methods: This retrospective study included 33 patients with locally recurrent nasopharyngeal carcinoma (stage rT1-2, partial rT3) underwent transoral Da Vinci robotic surgery between October 2017 and January 2020. There were 20 males and 11 females, with an average age of (47.9±10.5) years. The lesions were localized in nasopharyngeal cavity in 14 cases, with extending to parapharyngeal space in 6 cases and the floor of sphenoid sinus in 13 cases. Transnasal endoscopy was used to assist surgery if necessary. SPSS 25.0 statistical software was used for statistical analysis. Results: Transoral robotic nasopharyngectomy was successfully performed in all cases without conversion to open surgery, of which 13 cases were combined with transnasal endoscopic surgery. The average operation time was (126.2±30.0) min, ranging from 90 to 180 min. The postoperative pathological margin was R0 (31 cases) and R1 (2 cases), with no tumor residue. Complications of surgery mainly included symptoms of headache, nasal dryness and velopharyngeal insufficiency without nasopharyngeal hemorrhage. Follow-up time was from 3 to 54 months. One case had tumor recurrence 11 months after operation, 1 case had ipsilateral cervical lymph node metastasis 27 months after operation, 2 cases had distant metastasis and 1 case died of nasopharyngeal hemorrhage 3 months after operation. The 1-year, 2-year and 3-year overall survival rates were 97.0%, 96.0% and 92.9%, respectively and the local recurrence free rates were 97.0%, 95.7% and 91.7%, respectively. Conclusion: Transoral robotic nasopharyngectomy is safe and feasible for local recurrent nasopharyngeal carcinoma in selected patients, with higher local control rate and quality of life.

Outcome evaluation of non-penetrating trabecular surgery combined with suture trabeculotomy for the treatment of primary congenital glaucoma / 中华实验眼科杂志

Objective:To investigate the efficacy and safety of non-penetrating trabecular surgery combined with nearly 360-degree suture trabeculotomy for the treatment of primary congenital glaucoma (PCG).Methods:An observational case series study was conducted.A total of 29 cases (50 eyes) with PCG, including 21 males (35 eyes) and 8 females (15 eyes), were enrolled in Jiangsu Province Hospital and Nanjing Children's Hospital from January to November, 2019.The age of subjects ranged from 1 month to 4 years, and the median age was 6 months.Non-penetrating trabecular surgery was first performed in order to open the Schlemm canal.The cannulation and nearly 360-degree suture trabeculotomy were then performed with the twisted 6-0 polypropylene suture.Intraocular pressure (IOP), corneal diameter, cup-to-disc ratio (c/d) and complications were recorded preoperatively and 1 week, 1 month, 3 months, 6 months, 9 months, 12 months, and 24 months postoperatively, and the proportion of sutures successfully passed through the Schlemm canal and the success rate of operation were recorded.This study followed the Declaration of Helsinki.The study protocol was approved by an Ethics Committee of The First Affiliated Hospital of Nanjing Medical University (No.2019-SR-198). Written informed consent was obtained from the guardian of each subject prior to entering the study cohort.Results:Circumferential cannulation by suture was successfully performed in 90% of the subjects.The Harms trabeculotomy probe was applied in failed cases.Mean IOP was significantly lowered from preoperative (35.0±9.5) mmHg (1 mmHg=0.133 kPa) to (9.9±4.4), (10.0±4.2), (9.7±4.4), (9.0±2.9), (9.4±4.2), (9.3±3.3) and (9.5±3.8) mmHg at postoperative 1 week, 1 month, 3 months, 6 months, 9 months, 12 months and 24 months, respectively ( F=141.56, P<0.01). Mean corneal diameter was significantly reduced from preoperative (13.7±1.4) mm to (13.3±1.4), (12.9±1.4), (12.8±1.3), (12.7±1.2), (12.6±1.1), (12.6±1.1) and (12.8±0.4) mm at postoperative 1 week, 1 month, 3 months, 6 months, 9 months, 12 months and 24 months, respectively ( F=4.55, P<0.01). Mean c/d was significantly reduced from preoperative 0.81±0.15 to 0.55±0.22, 0.48±0.23, 0.45±0.22, 0.43±0.21, 0.41±0.20, 0.40±0.21 and 0.31±0.19 at postoperative 1 week, 1 month, 3 months, 6 months, 9 months, 12 months and 24 months, respectively ( F=21.07, P<0.01). Forty-two eyes (93.3%) achieved complete success and 45 eyes (100%) achieved qualified success at postoperative 12 months.No severe complications were observed during or after surgery. Conclusions:Non-penetrating trabecular surgery combined with nearly 360-degree suture trabeculotomy can effectively treat patients with PCG without any severe complications.

Self-assembly of a Mixed Valence Copper Triangular Prism and Transformation to Cage Triggered by an External Stimulus.

A triangular prismatic metal-organic cage based on mixed valence copper ions has been designed and synthesized by using metallocycle panels and pillar ligands. The triangular prism will be quickly transformed to a 10-nuclear cage upon an external chemical stimulus, which features a bicapped square antiprism structure. This prismatic cage can act as a catalyst for oxidation of aromatic alcohols to their corresponding aromatic aldehydes with high yields at room temperature under O2 atmosphere.

Pre-mixed nitrous oxide/oxygen mixture treatment of pain induced by postoperative dressing change for perianal abscess: Study protocol for a randomized, controlled trial.

AIM: This study aims to evaluate the safety and analgesic efficacy of pre-mixed nitrous oxide/oxygen mixture treatment of pain induced by dressing change for perianal abscess. DESIGN: This protocol is a randomized, double-blind, placebo-controlled trial. METHODS: This study will be implemented in the Hospital of Traditional Chinese Medicine. Subjects enrolled in this study are hospitalized patients who suffered from moderate to severe pain due to dressing change after incision and drainage. Two hundred patients will be selected and randomly assigned to either an intervention or a control group. The intervention group will get routine pain treatment plus pre-mixed nitrous oxide/oxygen mixture treatment and the control group will be treated with routine pain management plus medical air treatment. All these patients, medical staff and investigators are blind to the nature of the gas in each cylinder, which is randomized. Data will be collected at baseline (T0), 5 min (T1) after the starting of intervention and 5 min post intervention (T2) for each group. The primary outcome is the level of pain relief at T1 and T2. The secondary outcomes cover physiological parameters, adverse events, satisfaction of patients and health professionals and the acceptance from patients. DISCUSSION: Results of this study will be discussed and the safety and effect of nitrous oxide/oxygen treatment of pain induced by dressing change will be proven. IMPACT: When the finding of this study has an active effect on the treatment of pain caused by dressing change, it may provide more options for nursing staff to choose nurse-led analgesia techniques and then improving the level and quality of pain care as well as patients' overall satisfaction with the Anorectal Department in China.

Functionality is not an independent prognostic factor for pancreatic neuroendocrine tumors.

BACKGROUND: Pancreatic neuroendocrine neoplasms (pNENs) that produce hormones leading to symptoms are classified as functional tumors, while others are classified as nonfunctional tumors. The traditional view is that functionality is a factor that affects the prognosis of pNEN patients. However, as the sample sizes of studies have increased, researches in recent years have proposed new viewpoints. AIM: To assess whether functionality is an independent factor for predicting the prognosis of pNEN patients. METHODS: From January 2004 to December 2016, data of patients who underwent surgery at the primary site for the treatment of pNENs from the Surveillance, Epidemiology, and End Results (SEER) database and West China Hospital database were retrospectively analyzed. RESULTS: Contemporaneous data from the two databases were analyzed separately as two cohorts and then merged as the third cohort to create a large sample that was suitable for multivariate analysis. From the SEER database, age (P = 0.006) and T stage (P < 0.001) were independent risk factors affecting the survival. From the West China Hospital database, independent prognostic factors were age (P = 0.034), sex (P = 0.032), and grade (P = 0.039). The result of the cohort consisting of the combined populations from the two databases showed that race (P = 0.015), age (P = 0.002), sex (P = 0.032) and T stage (P < 0.001) were independent prognostic factors. In the West China Hospital database and in the total population, nonfunctional pNETs and other functional pNETs tended to have poorer prognoses than insulinoma. However, functionality was not associated with the survival time of patients with pNETs in the multivariate analysis. CONCLUSION: Functionality is not associated with prognosis. Race, age, sex, and T stage are independent factors for predicting the survival of patients with pNETs.

Cognitive improvements and reduction in amyloid plaque deposition by saikosaponin D treatment in a murine model of Alzheimer's disease.

Alzheimer's disease (AD), is a severe neurodegenerative disease that currently lacks an optimally effective therapeutic agent for its management. Saikosaponin D (SSD) is a component extracted from the herb Bupleurum falcatum that is commonly used in Chinese medicine. Although SSD has been reported to exert neuroprotective effects, its pharmacological role in AD has not been previously elucidated. Therefore, the aim of the present study was to investigate whether SSD treatment improves the cognitive function and pathological features of 3xTg mice, a triple-transgenic mouse model of AD that displays classical pathological features of AD. The effects of SSD treatment on the behavioral, histological and physiological features of the animal were quantified. Results from the behavioral experiments on the SSD-treated 3xTg mice identified a significant reduction in memory impairment. In addition, histological staining results indicated that SSD application could preserve the morphology of neurons, reduce apoptosis and significantly inhibit amyloid-ß deposition in the hippocampus of 3xTg mice. SSD treatment also decelerated the activation of microglia and astrocytes in the hippocampus of 3xTg mice, possibly via the inhibition of the NF-κB signal transduction pathway. Therefore, the present study demonstrated the protective effects of SSD against progressive neurodegeneration and identified the potential underlying pharmacological mechanism. It was speculated that SSD may serve as a possible therapeutic agent in AD treatment in the future.

Optical coherence tomography guided treatment avoids stenting in an antiphospholipid syndrome patient: A case report.

BACKGROUND: Increasing attention has been paid to acute myocardial infarction (AMI) in young female patients for whom secondary factors should be considered during the diagnostic process. Anti-phospholipid syndrome (APS), a rare autoimmune disease that is most common in young female patients, is reportedly related to AMI. To date, coronary interventions, particularly stenting, remains controversial in this special clinical scenario. CASE SUMMARY: A 26-year-old female patient was admitted to hospital for acute chest pain, palpitations, and dyspnea. She had a past medical history of APS and pulmonary embolism. Coronary angiography showed acute occlusion of the proximal left anterior descending artery. After repeated thrombus aspirations, residual thrombus and mild stenosis were found in the proximal left anterior descending artery. Optical coherence tomography (OCT) was done, which confirmed the non-atherosclerosis coronary thrombosis and an intact intima in this patient. Deferring or avoiding stenting based on follow-up intracoronary findings with intensified antithrombotic treatment was chosen. One week later, coronary angiography and OCT confirmed an intact intima with no injury and no residual thrombus. The 3-mo telephone follow-up reported a good prognosis. CONCLUSION: APS can cause acute non-atherosclerosis coronary thrombosis which presents as an AMI in young female patients. Intracoronary OCT findings can guide interventional strategies in this special clinical scenario.

Idiopathic hypereosinophilic syndrome associated with rapid progression of cardiac, pulmonary and skin infiltration.

Idiopathic hypereosinophilic syndrome (IHES) is a rare myeloproliferative disease characterised by multisystem dysfunction and persistent, extreme eosinophilia of unknown cause. Here we present a 42-year-old patient complaining of moderate to severe chest pain and shortness of breath, and typical ischaemic electrocardiography changes were recorded. He was initially suspected of having acute coronary syndrome, however the coronary angiogram excluded coronary abnormalities. Bone marrow biopsy, left ventriculography, transthoracic echocardiography and cardiac magnetic resonance examinations confirmed the diagnosis of IHES and IHES-mediated cardiac involvement. The patient's illness was alleviated during the first hospitalisation, whereas it had rapidly worsened one month after discharge. In addition, simultaneous pulmonary and skin-infiltrating lesions occurred during the second hospitalisation. The patient's condition improved markedly with combined glucocorticoid, hydroxyurea and warfarin therapy, as well as treatment for heart failure. In this report the diagnostic modalities and treatment strategies for IHES are discussed and reviewed.

Self-assembly of mixed-valence and heterometallic metallocycles: efficient catalysts for the oxidation of alcohols to aldehydes in ambient air.

Two mixed-valence CuII/CuI and two heterometallic CuII/AgI metallocycles have been synthesized by the assembly of designed metalloligands and CuI/AgI ions, respectively. The CuII/CuI metallocycle can catalyze the oxidation of alcohols to aldehydes mediated by a co-catalyst, TEMPO (2,2,6,6-tetramethylpiperdine-1-oxyl), with ambient air as an oxidant, while the CuII/AgI metallocycle has no catalytic effect.

Rescue treatment and follow-up intervention of a left main acute myocardial infarction with typical carina shift under 3D optical coherence tomography: A case report.

BACKGROUND: Coronary intervention for bifurcation lesions is still challenging for interventional cardiologists. Left main (LM) bifurcation lesions have a higher risk due to the vast blood supply in this area and treatment choice is difficult. Ostial compromise of the side branch decreases patient prognosis, and its management is still an issue despite the different strategies and devices available. CASE SUMMARY: A 42-year-old male patient was admitted to hospital due to chest pain and syncope. Coronary angiography showed acute LM occlusion. Following thrombus aspiration, a LM bifurcation lesion remained. Coronary angiography was repeated one week later, and at the same time, 3D optical coherence tomography (OCT) was carried out to better show the geometry of the bifurcation, which confirmed that the stenosis in the ostial left circumflex artery was caused by a long carina. After assessment of the plaque characteristics and the minimum lumen area, the cross-over strategy, kissing balloon inflation and proximal optimization technique were chosen to treat the bifurcation lesion. A "moving" carina was found twice during the intervention. Good stent apposition and expansion were confirmed by OCT after proximal optimization technique. The three-month follow-up showed good recovery and normal cardiac function. CONCLUSION: 3D-OCT can facilitate decision-making for coronary interventions in patients with critical bifurcation lesions.

Immersive virtual reality as analgesia for women during hysterosalpingography: study protocol for a randomized controlled trial.

BACKGROUND: Hysterosalpingography (HSG) is an accepted radiologic diagnostic modality for initial infertility workup, and is generally considered uncomfortable and painful. However, the management of pain related to HSG remains inefficient. As an emerging nonpharmacologic and noninvasive pain control strategy, virtual reality (VR) distraction has been successfully used in areas such as burns, blunt force trauma, hospital-based needle procedures, dental/periodontal procedures, and urological endoscopy patients. This study aims to evaluate the analgesic effect of VR during HSG. METHODS/DESIGN: A single-center, parallel-group, randomized controlled trial will be carried out in the Radiology Department of Yinchuan Women and Children Healthcare Hospital, Yinchuan. A total of 200 participants who are scheduled for HSG will be enrolled in this study. The participants will be randomized (1:1) into two groups: a VR group and a blank control group. The VR group will receive routine care plus immersive VR intervention and the blank control group will receive routine care. Outcomes will be monitored at baseline, immediately after HSG and 15 min after HSG for each group. The primary outcome is the worst pain score during HSG by a visual analog scale (VAS). The secondary outcomes include: affective pain, cognitive pain, and anxiety during the HSG procedure; worst pain within 15 min after HSG; patient satisfaction and acceptance with pain management; physiological parameters; adverse effects; HSG results; and immersion perception score of the VR system (for the VR condition only). DISCUSSION: This study will focus on exploring a simply operated, noninvasive and low-cost analgesia during the HSG procedure. The results of this trial will provide data on the feasibility and safety of VR distraction therapy during HSG. TRIAL REGISTRATION: Chinese Clinical Trial Register, ChiCTR1900021342. Registered on 16 February 2019.

Tubulin Inhibitors Binding to Colchicine-Site: A Review from 2015 to 2019.

Due to the three domains of the colchicine-site which is conducive to the combination with small molecule compounds, colchicine-site on the tubulin has become a common target for antitumor drug development, and accordingly, a large number of tubulin inhibitors binding to the colchicine-site have been reported and evaluated over the past years. In this study, tubulin inhibitors targeting the colchicine-site and their application as antitumor agents were reviewed based on the literature from 2015 to 2019. Tubulin inhibitors were classified into ten categories according to the structural features, including colchicine derivatives, CA-4 analogs, chalcone analogs, coumarin analogs, indole hybrids, quinoline and quinazoline analogs, lignan and podophyllotoxin derivatives, phenothiazine analogs, N-heterocycle hybrids and others. Most of them displayed potent antitumor activity, including antiproliferative effects against Multi-Drug-Resistant (MDR) cell lines and antivascular properties, both in vitro and in vivo. In this review, the design, synthesis and the analysis of the structure-activity relationship of tubulin inhibitors targeting the colchicine-site were described in detail. In addition, multi-target inhibitors, anti-MDR compounds, and inhibitors bearing antitumor activity in vivo are further listed in tables to present a clear picture of potent tubulin inhibitors, which could be beneficial for medicinal chemistry researchers.

Mechanism of Liuwei Dihuangtang on Learning and Memory in Depressive Rats / 中国实验方剂学杂志

Objective::To investigate the effect and possible mechanism of Liuwei Dihuangtang on memory impairment in rats with chronic depression. Method::Female Wistar rats were randomly divided into normal group (normal saline), chronic unpredictable mild stress (CUMS) model group (normal saline), and low, medium and high-dose Liuwei Dihuangtang groups (2.60, 7.81, 23.50 g·kg-1·d-1). Except for the normal group, all of the other groups were included in the chronic unpredictable mild stress model. Weight were measured every week, changes in their behavioral indicators were observed. The mRNA expressions of G protein-coupled estrogen receptor (GPR30), phosphatidylinositol 3-kinase(PI3K), cyclic adenosine monophosphate response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in the rat hippocampus were determined by real-time fluorescence quantification polymerase chain reaction (Real-time PCR). The concentration of serum estrogen was detected by enzyme-linked immunosorbent assay (ELISA) method. Result::Compared with normal group, model group showed decreases in weight, activity and interest. Liuwei Dihuangtang (2.60, 7.81, 23.50 g·kg-1) significantly increased the sucrose preference of CUMS rats (P<0.01) and standing times in the open field test (P<0.01), doses of 7.81, 23.50 g·kg-1 significantly increased the total distance of the open field test (P<0.05, P<0.01), doses of 2.60, 7.81 g·kg-1 shortened the latency of water maze experiment (P<0.01), and dose of 7.81 g·kg-1 increased serum estrogen concentration (P<0.05). The mRNA expressions of GPR30, PI3K, CREB and BDNF in hippocampus of CUMS model group decreased significantly (P<0.05, P<0.01), but the mRNA expression levels of GPR30, CREB in hippocampus of 2.60 g·kg-1 dose Liuwei Dihuangtang group increased significantly (P<0.05, P<0.01), and the mRNA expression levels of GPR30, PI3K, CREB, BDNF in hippocampus of 7.81 g·kg-1 dose group increased significantly as well (P<0.05, P<0.01). Conclusion::Liuwei Dihuangtang has effect in resisting depression, and reversing depression-like behavior and learning and memory impairment in CUMS rats, with the best effect in the medium-dose Liuwei Dihuangtang group. Its mechanism may be related to increase of serum estrogen and mRNA expressions of GPR30, PI3K, CREB and BDNF in rat hippocampus.