Inetetamab combined with pyrotinib and chemotherapy in the treatment of breast cancer brain metastasis: A case report.

BACKGROUND: Breast cancer brain metastasis (BCBM) is an advanced breast disease that is difficult to treat and is associated with a high risk of death. Patient prognosis is usually poor, with reduced quality of life. In this context, we report the case of a patient with HER-2-positive BCBM treated with a macromolecular mAb (inetetamab) combined with a small molecule tyrosine kinase inhibitor (TKI). CASE SUMMARY: The patient was a 58-year-old woman with a 12-year history of type 2 diabetes. She was compliant with regular insulin treatment and had good blood glucose control. The patient was diagnosed with invasive carcinoma of the right breast (T3N1M0 stage IIIa, HER2-positive type) through aspiration biopsy of the ipsilateral breast due to the discovery of a breast tumor in February 2019. Immunohistochemistry showed ER (-), PR (-), HER-2 (3+), and Ki-67 (55-60%+). Preoperative neoadjuvant chemotherapy, i.e., the AC-TH regimen (epirubicin, cyclophosphamide, docetaxel-paclitaxel, and trastuzumab), was administered for 8 cycles. She underwent modified radical mastectomy of the right breast in November 2019 and received tocilizumab targeted therapy for 1 year. Brain metastasis was found 9 mo after surgery. She underwent brain metastasectomy in August 2020. Immunohistochemistry showed ER (-) and PR. (-), HER-2 (3+), and Ki-67 (10-20%+). In November 2020, the patient experienced headache symptoms. After an examination, tumor recurrence in the original surgical region of the brain was observed, and the patient was treated with inetetamab, pyrotinib, and capecitabine. Whole-brain radiotherapy was recommended. The patient and her family refused radiotherapy for personal reasons. In September 2021, a routine examination revealed that the brain tumor was considerably larger. The original systemic treatment was continued and combined with intensity-modulated radiation therapy for brain metastases, followed by regular hospitalization and routine examinations. The patient's condition is generally stable, and she has a relatively high quality of life. This case report demonstrates that in patients with BCBM and resistance to trastuzumab, inetetamab combined with pyrotinib and chemotherapy can prolong survival. CONCLUSION: Inetetamab combined with small molecule TKI drugs, chemotherapy and radiation may be an effective regimen for maintaining stable disease in patients with BCBM.

[Community structure and species composition of typical Quercus variabilis natural secondary forest at the northern foothills of the Qinling Mountains, China]. / ç§¦å²­åŒ—éº“å ¸åž‹æ “çš®æ Žå¤©ç„¶æ¬¡ç”Ÿæž—ç¾¤è½ç»“æž„ä¸Žç‰©ç§ç»„æˆ.

We investigated species composition and community structure of a typical Quercus variabilis natural secondary forest in the northern foothills of the Qinling Mountains, within the dynamic monitoring plot of deciduous broad-leaved forest at the Louguantai experimental forest farm in Zhouzhi County, Shaanxi Province. The results showed that there were 3162 individual woody plants with diameter at breast height ≥1 cm in the plot, which were belonged to 42 species, 36 genera, and 25 families. The community genus's areal type was dominated by the temperate component, which accounted for 44.4%, and followed by the tropical component. The community was dominated by several tree species. The top three species with respect to importance value were Q. variabilis, Pinus tabuliformis, and Quercus aliena, with the sum of their importance value being 64.7%. The average DBH of all woody plants was 7.58 cm. The distribution of all individuals and dominant species in the tree layer was approximately normal, with more medium-size individuals. The community structure was stable. The community was poorly renewed, with a trend of population decline. Biodiversity indices varied considerably among different plots, being lower than those of subtropical broad-leaved evergreen forests. There was a significant correlation between community species distribution and environmental factors. Soil and topography explained 42.4% of the variation in community distribution. Altitude and soil alkali hydrolysable nitrogen had a significant effect on community distribution. Altitude, soil total phosphorus, and organic matter content significantly affected the species diversity of Q. variabilis communities. The stronger adaptability of Q. variabilis populations allowed them to become dominant in low-nutrient environments, which limited species diversity in the community.

[Reflections on supervision strategies of new Tibetan drug registration].

Tibetan medicine is an essential part of Chinese medicine and has unique theoretical experience and therapeutic advantages. According to the development principle of inheriting the essence, sticking to the truth, and keeping innovative, the supervision department should give clear and reasonable guidance considering the characteristics of Tibetan medicine, establish a standard system for quality control, clinical verification and evaluation, and accelerate the research and commercialization of new drugs. In view of the needs of drug supply-side reform and the current situation of Tibetan medicine and new pharmaceutical research, we ponder and provide suggestions on the confusion faced by the current supervision of Tibetan drug registration, hoping to contribute to the supervision strategy of Tibetan drug registration and the high-quality development of Tibetan medicine industry.

Photochromic Semiconductors: Bottom-Up Strategy to Construct Type II-Stacking Viologen π-Aggregates.

Semiconductor conductivities depend largely on the crystal structures and the associated electronic structures. If the electronic structures can be switched reversibly in the same crystal structure, then a drastic conductivity change may be controllable. The effect of electron transfer (ET) on semiconductor conductivity remained elusive so far. In this work, a series of two pillared inorganicorganic hybrid photochromic semiconductors (PSCs), [(CQ)Pb3X6(H2O)]·2H2O [X = Cl (1) and Br (2), CQ = N-4,4'-bipyridiniopropionate (viologen)], with II-stacking viologen π-aggregates, are constructed by a bottom-up self-assembly strategy through inorganic skeleton-directed intercalation and intermolecular noncovalent interaction. The conductivities are abnormally "invariant" after photoinduced ET, breaking the convention that the generation of radicals favors conductivity. The abnormally "invariant" conductivities are mainly derived from approximate electronic couplings before and after ET between II-stacking viologen π-aggregates.

High expression of long noncoding RNA plasmacytoma variant translocation 1 is an independent risk factor for recurrence after radiofrequency ablation in atrial fibrillation patients.

Atrial fibrillation (AF) is a common arrhythmia. Radiofrequency ablation (RFA) is the major AF treatment. Long noncoding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) is related to AF diagnosis. This study explored the clinical roles of PVT1 in AF. Totally, 168 AF patients and 100 healthy controls were selected. Plasma lncRNA PVT1 in AF patients before/after RFA was detected and the diagnostic efficacy and postoperative recurrence prediction value in AF were analyzed. Effects of plasma PVT1 expression on AF recurrence and its correlation with transforming growth factor beta 1 (TGF-ß1) in the recurrence and non-recurrence groups were analyzed by Pearson coefficient. The risk factors of AF recurrence were evaluated. Plasma PVT1 was highly expressed in AF patients and diminished after RFA. PVT1 level >1.255 assisted AF diagnosis. The plasma PVT1 level in the recurrence group was higher than that of the non-recurrence group. PVT1 level >1.525 assisted the prediction for postoperative recurrence. AF postoperative recurrence incidence in high PVT1 expression group was clearly higher than that in low PVT1 expression group, and plasma PVT1 expression in patients of the recurrence and non-recurrence groups was positively correlated with TGF-ß1 content. High PVT1 expression was an independent risk factor for postoperative recurrence. Briefly, high PVT1 level assisted AF diagnosis and recurrence evaluation after RFA and was an independent risk factor for AF postoperative recurrence.

Multi-omics characterization of the unsaturated fatty acid biosynthesis pathway in colon cancer.

The biosynthesis of unsaturated fatty acids is involved in the initiation and progression of colon adenocarcinoma (COAD). In this study, we aimed to investigate the multi-omics characteristics of unsaturated fatty acid biosynthesis-related genes and explore their prognostic value in colon cancer by analyzing the data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. An unsaturated fatty acid biosynthesis pathway related-genes enrichment score (BUFAS) was constructed utilizing the single sample gene set enrichment analysis (ssGSEA). We discovered that a high BUFAS was associated with longer overall survival (OS) in both the training and the validation sets. Multivariable analysis including the clinical characteristics further verified the independent prognostic value of the BUFAS in both the TCGA-COAD and the GSE39582 datasets. In addition, GSEA analysis revealed that BUFAS was positively associated with several signaling pathways, including MTORC1, peroxisome, and pathways related to fatty acid metabolism, while was negatively associated with other signaling pathways, such as hedgehog, NOTCH, and Wnt/beta-catenin pathway. Furthermore, in the COAD cell lines of the Genomics of Drug Sensitivity in Cancer (GDSC) database, we found that BUFAS was positively correlated with the drug sensitivities of cisplatin, gemcitabine, camptothecin, lapatinib, and afatinib, while was negatively correlated with that of ponatinib. Moreover, in the COAD single-cell transcriptomic dataset (GSE146771), the BUFAS varied among different cell types and was enriched in mast cells and fibroblasts. Taken together, the BUFAS we constructed could be used as an independent prognostic signature in predicting the OS and drug resistance of colon cancer. Unsaturated fatty acid biosynthesis pathway might serve as potential therapeutic targets for cancer treatment.

A Game of Infection - Song of Respiratory Viruses and Interferons.

Humanity has experienced four major pandemics since the twentieth century, with the 1918 Spanish flu, the 2002 severe acute respiratory syndrome (SARS), the 2009 swine flu, and the 2019 coronavirus disease (COVID)-19 pandemics having the most important impact in human health. The 1918 Spanish flu caused unprecedented catastrophes in the recorded human history, with an estimated death toll between 50 - 100 million. While the 2002 SARS and 2009 swine flu pandemics caused approximately 780 and 280,000 deaths, respectively, the current COVID-19 pandemic has resulted in > 6 million deaths globally at the time of writing. COVID-19, instigated by the SARS - coronavirus-2 (SARS-CoV-2), causes unprecedented challenges in all facets of our lives, and never before brought scientists of all fields together to focus on this singular topic. While for the past 50 years research have been heavily focused on viruses themselves, we now understand that the host immune responses are just as important in determining the pathogenesis and outcomes of infection. Research in innate immune mechanisms is crucial in understanding all aspects of host antiviral programmes and the mechanisms underpinning virus-host interactions, which can be translated to the development of effective therapeutic avenues. This review summarizes what is known and what remains to be explored in the innate immune responses to influenza viruses and SARS-CoVs, and virus-host interactions in driving disease pathogenesis. This hopefully will encourage discussions and research on the unanswered questions, new paradigms, and antiviral strategies against these emerging infectious pathogens before the next pandemic occurs.

Plasticity of the spinal glymphatic system in male SD rats with painful diabetic neuropathy induced by type 2 diabetes mellitus.

The glymphatic system is a recently discovered glial-dependent macroscopic interstitial waste clearance system that promotes the efficient elimination of soluble proteins and metabolites from the central nervous system. Its anatomic foundation is the astrocytes and aquaporin-4 (AQP4) water channels on the endfeet of astrocytes. The aim of this study is to evaluate the plasticity of the spinal glymphatic system in male SD rats with painful diabetic neuropathy (PDN) induced by type 2 diabetes mellitus. PDN rats were modeled under a high-fat and high-glucose diet with a low dose of streptozotocin. MRI was applied to observe the infiltration and clearance of contrast to indicate the functional variability of the glymphatic system at the spinal cord level. The paw withdrawal threshold was used to represent mechanical allodynia. The numerical change of glial fibrillary acidic protein (GFAP) positive astrocytes was assessed and the polarity reversal of AQP4 protein was measured by immunofluorescence. As a result, deceased contrast infiltration and clearance, enhanced mechanical allodynia, increased number of GFAP positive astrocytes, and reversed polarity of AQP4 protein were found in the PDN rats. The above molecular level changes may contribute to the impairment of the spinal glymphatic system in PDN rats. This study revealed the molecular and functional variations of the spinal glymphatic system in PDN rats and for the first time indicated that there might be a correlation between the impaired spinal glymphatic system and PDN rats.

Triple-Wavelength Lasing with a Stabilized ß-LaBSiO5:Nd3+ Crystal.

Multi-wavelength lasers, especially the triple-wavelength laser around 1060 nm, could be produced by the 4F3/2 → 4I11/2 transition of Nd3+ and present numerous challenges and opportunities in the field of optoelectronics. The Nd3+-doped high-temperature phase of LaBSiO5 (ß-LBSO) is an ideal crystal to produce triple-wavelength lasers; however, the crystal growth is challenging because of the phase transition from ß-LBSO to low-temperature phase (α-LBSO) at 162 °C. This phase transition is successfully suppressed when the doping content of Nd3+ is larger than 6.3 at. %, and the Nd3+-doped ß-LBSO is stable at room temperature. The local disorder of BO4 tetrahedra due to Nd3+ doping is essential to the stabilization of ß-LBSO. For the first time, the ß-LBSO:8%Nd3+ crystal with a dimension of 1.8 × 1.8 × 1.8 cm3 is obtained through the top-seeded solution method. The crystal shows strong optical absorption in the range of 785-815 nm, matching well with the commercial laser diode pumping source. The optical emission of 4F3/2 → 4I11/2 splits into four peaks with the highest optical emission cross section of 2.14 × 10-20 cm2 at 1068 nm. The continuous-wave triple-wavelength generation of coherent light at 1047, 1071, and 1092 nm is achieved with the highest output power of 235 mW and efficiency of 12.1%.

Persistence of Antibody and Cellular Immune Responses in Coronavirus Disease 2019 Patients Over Nine Months After Infection.

BACKGROUND: The duration of humoral and T and B cell response after the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains unclear. METHODS: We performed a cross-sectional study to assess the virus-specific antibody and memory T and B cell responses in coronavirus disease 2019 (COVID-19) patients up to 343 days after infection. Neutralizing antibodies and antibodies against the receptor-binding domain, spike, and nucleoprotein of SARS-CoV-2 were measured. Virus-specific memory T and B cell responses were analyzed. RESULTS: We enrolled 59 patients with COVID-19, including 38 moderate, 16 mild, and 5 asymptomatic patients; 31 (52.5%) were men and 28 (47.5%) were women. The median age was 41 years (interquartile range, 30-55). The median day from symptom onset to enrollment was 317 days (range 257 to 343 days). We found that approximately 90% of patients still have detectable immunoglobulin (Ig)G antibodies against spike and nucleocapsid proteins and neutralizing antibodies against pseudovirus, whereas ~60% of patients had detectable IgG antibodies against receptor-binding domain and surrogate virus-neutralizing antibodies. The SARS-CoV-2-specific IgG+ memory B cell and interferon-γ-secreting T cell responses were detectable in more than 70% of patients. CONCLUSIONS: Severe acute respiratory syndrome coronavirus 2-specific immune memory response persists in most patients approximately 1 year after infection, which provides a promising sign for prevention from reinfection and vaccination strategy.

A Tellurium-Substituted Heteropolyniobate with Unique π-π Stacking and Ionic Conduction Property.

A tetratellurium-substituted heteropolyoxoniobate with the formula K2H[Cu(phen)(H2O)]4[Cu(phen)]2[(LiNb8Te4O40)]·34H2O (1; phen = 1,10-phenanthroline) was hydrothermally prepared and structurally characterized. The compound represents the first hexavalent tellurium-substituted Keggin-type polyoxometalate (POM) so far. What is more, the POM cluster in 1 can elaborately self-assemble into a stable supramolecular framework with an ion conduction property through unique intermolecular π-π stacking.

[Characteristics of extreme precipitation in Ansai District of Yan'an City, China.] / 延安市安塞区极端降水变化特征.

The extreme precipitation characteristics of Ansai District in 40 years was analyzed from the perspective of precipitation intensity and precipitation frequency with 11 extreme precipitation indices, based on daily precipitation data of Ansai Meteorological Station from 1980 to 2019. The trend of extreme precipitation in the future was predicted. The results showed that the extreme precipitation indicators generally showed a downward trend during 1980-2019. The downtrend of heavy precipitation days and simple daily precipitation intensity reached significant level, with their climate tendency slopes being -0.65 d·(10 a)-1, -0.32 mm·d-1·(10 a)-1, respectively. Except for consecutive wet days and extremely wet day precipitation, the other extreme precipitation indices had mutation points. After the mutation, most of them had a downward trend, with significant decreases of annual precipitation, moderate precipitation days, heavy precipitation days, very heavy precipitation days, very wet day precipitation, simple daily precipitation intensity. The correlation between the consecutive dry days and other indicators was low and negatively correlated with some indicators, while the consecutive wet days were only correlated with a few indicators. In addition, other extreme precipitation indicators were significantly correlated. Results of the Hurst index analysis showed that the trend of extreme precipitation in Ansai District was sustainable.

Machine learning to predict high-dose methotrexate-related neutropenia and fever in children with B-cell acute lymphoblastic leukemia.

Methotrexate (MTX), an antimetabolite for the treatment of leukemia, could cause neutropenia and subsequently fever, which might lead to treatment delay and affect prognosis. Here, we aimed to predict neutropenia and fever related to high-dose MTX using artificial intelligence. This study included 139 pediatric patients newly diagnosed with standard- or intermediate risk B-cell acute lymphoblastic leukemia. Fifty-seven SNPs of 16 genes were genotyped. Univariate and multivariate analysis were used to select SNPs and clinical covariates for model developing. Five machine learning algorithms combined with four resampling techniques were used to build optimal predictive model. The combination of random forest with adaptive synthetic appeared to be the best model for neutropenia (sensitivity = 0.935, specificity = 0.920, AUC = 0.927) and performed best for fever (sensitivity = 0.818, specificity = 0.924, AUC = 0.870). By machine learning, we have developed and validated comprehensive models to predict the risk of neutropenia and fever. Such models may be helpful for medical oncologists in quick decision-making.

Effect of low-concentration carbohydrate on patient-centered quality of recovery in patients undergoing thyroidectomy: a prospective randomized trial.

BACKROUND: At present, low-concentration carbohydrate is rarely used in minor trauma surgery, and its clinical efficacy is unknown. The aim of the study was to evaluate the effect of preoperative oral low-concentration carbohydrate on patient-centered quality of recovery in patients undergoing thyroidectomy using Quality of Recovery - 15 (QoR-15) questionnaire. METHODS: One hundred twenty patients were randomized to oral intake of 300 ml carbohydrate solution (CH group) or 300 ml pure water (PW group) 2 h before surgery or fasting for 8 h before surgery (F group). The QoR-15 questionnaire was administered to compare the quality of recovery at 1d before surgery (T0), 24 h, 48 h, 72 h after surgery (T1, T2, T3), and perioperative blood glucose was recorded. RESULTS: Compared to the F group, the QoR-15 scores were statistically higher in the CH and PW group at T1 (P < 0.05), and the enhancement of recovery quality reached the clinical significance at T1 in the CH group compared with the F group. Among the five dimensions of the QoR-15 questionnaire, physical comfort, physiological support and emotional dimension in the CH group were significantly better than the F group (P < 0.05) at T1. Besides, blood glucose of CH group was significantly lower than the PW group and F group at each time point after surgery. CONCLUSIONS: Low-concentration carbohydrate could decrease the incidence of postoperative hyperglycemia and improve the patient-centered quality of recovery on patients undergoing open thyroidectomy at the early stage postoperatively. TRIAL REGISTRATION: ChiCTR1900024731 . Date of registration: 25/07/2019.

A Comprehensive Comparison Between the Semi-sterile and Sterile Technique for Closed Reduction and Percutaneous Pinning of Pediatric Supracondylar Humerus Fractures.

Background: Supracondylar humerus fracture is the most common elbow fracture in children, which often requires closed reduction and percutaneous pinning (CRPP) procedure for full recovery. In addition to the traditional sterile technique with full prep and draping, the semi-sterile technique without sterile gowns and drapes has been suggested to be a viable alternative for CRPP. Methods: Here, we performed a retrospective study over a 3-year period to comprehensively evaluate the outcomes of the semi-sterile and the sterile techniques for CRPP in supracondylar humerus fractured patients. Demographic data, fracture type, nerve injury status and the type of preparation technique (semi-sterile vs. sterile) were recorded. Time of preparation and operation, costs and elbow recovery status were compared. Outcomes of the two techniques were compared with bivariate analysis. Results: In a total of 137 patients, we found that the semi-sterile technique could significantly reduce the total operation room usage time (80 ± 13 min vs. 94 ± 12 min, 15% reduction, P < 0.001) and costs of CRPP. Specifically, anesthesia and medical waste costs were reduced by 139 RMB (1,736 ± 128 vs. 1,875 ± 197, 7.4% reduction, P < 0.001) and 103.0 RMB (14.6 vs. 117.9) per operation, respectively. At the meantime, the infection rate and recovery efficiency (89 ± 10 vs. 91 ± 9 of the Mayo Elbow Performance Score, P = 0.352) were almost unchanged as compared to the sterile technique group. Conclusions: Our study suggests that the semi-sterile technique can be used as a cost-effective alternative for CRPP in supracondylar humerus fracture and even other bone-related non-surgical approaches. Level of Evidence: The present study is a retrospective cohort study with a level III of evidence.

The tumor immune microenvironment transcriptomic subtypes of colorectal cancer for prognosis and development of precise immunotherapy.

BACKGROUND: Biomarkers based on immune context may guide prognosis prediction. T-cell inactivation, exclusion, or dysfunction could cause unfavorable tumor microenvironments, which affect immunotherapy and prognosis. However, none of the immuno-biomarkers reported to date can differentiate colorectal-cancer (CRC) patients. Thus, we aimed to classify CRC patients according to the levels of T-cell activation, exclusion, and dysfunction in the tumor microenvironment. METHODS: RNAseq data of 618 CRC patients from The Cancer Genome Atlas and microarray data of 316 CRC patients from Gene Expression Omnibus were analysed using the Tumor Immune Dysfunction and Exclusion algorithm. Unsupervised clustering was used to classify patients. RESULTS: Based on the expression signatures of myeloid-derived suppressor cells, cancer-associated fibroblasts, M2-like tumor-associated macrophages, cytotoxic T-lymphocytes, and PD-L1, all patients were clustered into four subtypes: cluster 1 had a high level of immune dysfunction, cluster 2 had a low level of immune activation, cluster 3 had intense immune exclusion, and cluster 4 had a high level of immune activation and a moderate level of both dysfunction and exclusion signatures. Compared with cluster 1, the hazard ratios and 95% confidential intervals for overall survival were 0.63 (0.35-1.13) for cluster 2, 0.55 (0.29-1.03) for cluster 3, and 0.30 (0.14-0.64) for cluster 4 in multivariate Cox regression. Similar immune clustering and prognosis patterns were obtained upon validation in the GSE39582 cohort. In subgroup analysis, immune clustering was significantly associated with overall survival among stage I/II patients, microsatellite stable/instability-low patients, and patients not treated with adjuvant therapy. CONCLUSIONS: Our findings demonstrated that classifying CRC patients into different immune subtypes serves as a reliable prognosis predictor and may help to refine patient selection for personalized cancer immunotherapy.

Impact of household quarantine on SARS-Cov-2 infection in mainland China: A mean-field modelling approach.

The novel coronavirus, named SARS-Cov-2, has raged in mainland China for more than three months, and it causes a huge threat to people's health and economic development. In order to curb the SARS-Cov-2 prevalence, the Chinese government enacted a series of containment strategies including household quarantine, traffic restriction, city lockdowns etc. Indeed, the pandemic has been effectively mitigated, but the global transmission is not still optimistic. Evaluating such control measures in detail plays an important role in limiting SARS-Cov-2 spread for public health decision and policymakers. In this paper, based on the cumulative numbers of confirmed cases and deaths of SARS-Cov-2 infection, from January 31st to March 31st, announced by the National Health Commission of the People's Republic of China, we established a mean-field model, considering the substantial contact change under some restrictive measures, to study the dynamics of SARS-Cov-2 infection in mainland China. By the Metropolis-Hastings (M-H) algorithm of Markov Chain Monte Carlo numerical method, our model provided a good fitting to the overall trends of SARS-Cov-2 infections and discovers the transmission heterogeneities by some extreme containment strategies to some extent. The basic reproduction number was approximated to be 2.05 (95% CI [1.35,2.87]); the hospitalized cases arrived at the peak of 29766 (95% CI [29743,29868]) on February 7th (95% CI [Feb.6th, Feb.8th]). Importantly, we identified that the highest risk group of SARS-Cov-2 was the family of four, which has the biggest probability of degree distributions at such node, suggesting that contact patterns play an important role in curtailing the disease spread.

Antinociceptive effects of magnesium sulfate for monitored anesthesia care during hysteroscopy: a randomized controlled study.

BACKGROUND: Opioids are the most effective antinociceptive agents, they have undesirable side effects such as respiratory depressant and postoperative nausea and vomiting. The purpose of the study was to evaluate the antinociceptive efficacy of adjuvant magnesium sulphate to reduce intraoperative and postoperative opioids requirements and their related side effects during hysteroscopy. METHODS: Seventy patients scheduled for hysteroscopy were randomly divided into 2 groups. Patients in the magnesium group (Group M) received intravenous magnesium sulfate 50 mg/kg in 100 ml of isotonic saline over 15 min before anesthesia induction and then 15 mg/kg per hour by continuous intravenous infusion. Patients in the control group (Group C) received an equal volume of isotonic saline as placebo. All patients were anesthetized under a BIS guided monitored anesthesia care with propofol and fentanyl. Intraoperative hemodynamic variables were recorded and postoperative pain scores were assessed with verbal numerical rating scale (VNRS) 1 min, 15 min, 30 min, 1 h, and 4 h after recovery of consciousness. The primary outcome of our study was total amount of intraoperative and postoperative analgesics administered. RESULTS: Postoperative serum magnesium concentrations in Group C were significantly decreased than preoperative levels (0.86 ± 0.06 to 0.80 ± 0.08 mmol/L, P = 0.001) while there was no statistical change in Group M (0.86 ± 0.07 to 0.89 ± 0.07 mmol/L, P = 0.129). Bradycardia did not occur in either group and the incidence of hypotension was comparable between the two groups. Total dose of fentanyl given to patients in Group M was less than the one administered to Group C [100 (75-150) vs 145 (75-175) µg, median (range); P < 0.001]. In addition, patients receiving magnesium displayed lower VNRS scores at 15 min, 30 min, 1 h, and 4 h postoperatively. CONCLUSIONS: In hysteroscopy, adjuvant magnesium administration is beneficial to reduce intraoperative fentanyl requirement and postoperative pain without cardiovascular side effects. Our study indicates that if surgical patients have risk factors for hypomagnesemia, assessing and correcting magnesium level will be necessary. TRIAL REGISTRATION: ChiCTR1900024596 . date of registration: July 18th 2019.

All-inorganic open frameworks based on gigantic four-shell Ln@W8@Ln8@(SiW12)6 clusters.

A series of POM-based all-inorganic open frameworks, H9[Ln9W8(µ4-O)12(µ2-O)24(H2O)24](SiW12O40)3·60H2O (1-Ln, Ln = La, Pr and Nd), have been fabricated and structurally characterized for the first time. The unique architectures are constructed from nanoscale four-shell Ln@W8@Ln8@(SiW12)6 clusters. Additionally, the porous nature of the frameworks has also been investigated.

Combination of electrical stimulation and bFGF synergistically promote neuronal differentiation of neural stem cells and neurite extension to construct 3D engineered neural tissue.

OBJECTIVE: The construction of in vitro three-dimensional (3D) neural tissue has to overcome two main types of challenges: (1) How to obtain enough number of functional neurons from stem cells in 3D culture; (2) How to wire those lately developed neurons into functional neural networks. Here, we describe the potential of using direct current (DC) electric field (EF) together with basic fibroblast growth factor (bFGF) synergistically in promoting neural stem cell (NSC) neuronal differentiation following by directing neurite outgrowth in the 3D neural tissue construction. APPROACH: By adjusting the electrical stimulation setup in this study, long-term electrical stimulation could be present in vitro. At an EF strength of 150 mV mm-1, cell responses, including cell viability, neuronal differentiation, cell morphology, the length of neuronal processes, synaptic structure and neural network formation, were quantified and analyzed. MAIN RESULTS: Analysis revealed that NSCs showed no significant cell death after certain EF treatments. EF-stimulated NSCs in 3D Matrigel mainly differentiated into neurons, but unlike NSCs in two-dimensional conditions, their processes were flat and stunted. When combined with bFGF, EF stimulation provided appropriate bioactive cues to establish engineered neural tissue with a proper neuronal cell number, highly branched neurites, and a well-developed neuronal network. SIGNIFICANCE: It is for the first time the synergistic effects of EF and bFGF stimulation have been evaluated in inducing the differentiation of NSCs into neurons and the acquisition of long neurites in a culture environment of in vitro 3D model. These optimized conditions may allow a well-developed neuronal network to be established within hydrogel droplets.