Personalized 3D Printed Tooth-Supported Template as a Novel Strategy for Radiofrequency Thermocoagulation for Trigeminal Neuralgia After the Failure of CT-Guided Puncture.

Background: Trigeminal neuralgia (TN) is a common form of craniofacial pain, and Radiofrequency thermocoagulation (RFT) has become a commonly utilized treatment modality for TN. However, the complex anatomical configuration of the maxillofacial region and the difficulties inherent in positioning the neck in a hyperextended manner can present challenges for CT-guided punctures. Aim: The objective of this study is to assess the effectiveness and safety of 3D printed tooth-supported template(3D-PTST) guided RFT in patients who have previously undergone unsuccessful CT-guided puncture. Methods: Patients with TN undergoing RFT at the Department of Pain Medicine, PLA General Hospital, from January 2018 to January 2023, were assessed. 3D-PTST guided RFT was employed as an alternative when percutaneous puncture failed. Clinical, demographic, and follow-up data were collected. The duration of the procedure was determined by subtracting the time of anesthesia administration from the time of surgical drape removal. Pain intensity was assessed using the Numerical Rating Scale-11 scale. Treatment effects were evaluated utilizing the Barrow Neurological Institute scale. Incidences of complications related to RFA were documented. Results: Six TN patients underwent 3D-PTST guided RFT. With tooth-supported template guidance, five patients achieved therapeutic target puncture in one attempt with one CT scan. One patient required two attempts with two CT scans. Operation duration ranged from 18 to 46 mins (mean 30 mins). All completed 3D-PTST-guided RFT without difficulty, significantly improving pain symptoms. Four patients had no pain recurrence at 12, 18, 36 and 37 months follow-up, respectively. Recurrence occurred in two patients (at 1 and 13 months). No serious treatment-related complications were observed. Conclusion: 3D-PTST guided RFT is an effective, repeatable, safe, and minimally invasive treatment method for patients with TN who have failed due to difficulty in puncture.

How incubation temperature affects hatchling performance in reptiles: an integrative insight based on plasticity in metabolic enzyme.

Evaluating the effects of temperature variations on animals plays an important role in understanding the threat of climate warming. The effects of developmental temperature on offspring performance are critical in evaluating the effects of warming temperatures on the fitness of oviparous species, but the physiological and biochemical basis of this developmental plasticity is largely unknown. In this study, we incubated eggs of the turtle Pelodiscus sinensis at low (24 °C), medium (28 °C), and high (32 °C) temperatures, and evaluated the effects of developmental temperature on offspring fitness, and metabolic enzymes in the neck and limb muscles of hatchlings. The hatchlings from eggs incubated at the medium temperature showed better fitness-related performance (righting response and swimming capacity) and higher activities of metabolic enzymes (hexokinase, HK; lactate dehydrogenase, LDH) than hatchlings from the eggs incubated at high or low temperatures. In addition, the swimming speed and righting response were significantly correlated with the HK activities in limb (swimming speed) and neck (righting response) muscles, suggesting that the developmental plasticity of energy metabolic pathway might play a role in determining the way incubation temperature affects offspring phenotypes. Integrating the fitness-related performance and the activities of metabolic enzymes, we predict that the P. sinensis from high latitude would not face the detrimental effects of climate warming until the average nest temperatures reach 32 °C.

Salidroside ameliorates acute liver transplantation rejection in rats by inhibiting neutrophil extracellular trap formation.

Acute rejection is an important factor affecting the survival of recipients after liver transplantation. Salidroside has various properties, including anti-inflammatory, antioxidant, and hepatoprotective properties. This study aims to investigate whether salidroside can prevent acute rejection after liver transplantation and to examine the underlying mechanisms involved. An in vivo acute rejection model is established in rats that are pretreated with tacrolimus (1 mg/kg/d) or salidroside (10 or 20 mg/kg/d) for seven days after liver transplantation. In addition, an in vitro experiment is performed using neutrophils incubated with salidroside (1, 10, 50 or 100 µM). Hematoxylin-eosin staining, terminal deoxynucleotidyl transferase dUTP nick-end labeling staining, immunosorbent assays, immunofluorescence analysis, Evans blue staining, and western blot analysis are performed to examine the impact of salidroside on NET formation and acute rejection in vitro and in vivo. We find that Salidroside treatment reduces pathological liver damage, serum aminotransferase level, and serum levels of IL-1ß, IL-6, and TNF-α in vivo. The expressions of proteins associated with the HMGB1/TLR-4/MAPK signaling pathway (HMGB1, TLR-4, p-ERK1/2, p-JNK, p-P38, cleaved caspase-3, cleaved caspase-9, Bcl-2, Bax, IL-1ß, TNF-α, and IL-6) are also decreased after salidroside treatment. In vitro experiments show that the release of HMGB1/TLR-4/MAPK signaling pathway-associated proteins from neutrophils treated with lipopolysaccharide is decreased by salidroside. Moreover, salidroside inhibits NETosis and protects against acute rejection by regulating the HMGB1/TLR-4/MAPK signaling pathway. Furthermore, salidroside combined with tacrolimus has a better effect than either of the other treatments alone. In summary, salidroside can prevent acute liver rejection after liver transplantation by reducing neutrophil extracellular trap development through the HMGB1/TLR-4/MAPK signaling pathway.

Design of Eu3+-Doped Fluoride Phosphor with Zero Thermal Quenching Property Based on Density Functional Theory.

Although being applied in various fields, white light emitting diodes (WLEDs) still have drawbacks that urgently need to be conquered: the luminescent intensity of commercial phosphors sharply decreases at working temperature. In this study, we calculated the forming energy of defects and confirmed that the VNa defect state can stably exist in ß-NaGdF4, by density functional theory (DFT) calculation. Furthermore, we predicted that the VNa vacancies would provide a zero thermal quenching (ZTQ) property for the ß-NaGdF4-based red-light phosphor. Then, a series of ß-NaGdF4:xEu3+ and ß-NaGdF4:0.25Eu3+,yYb3+ red-light phosphors were synthesized by the hydrothermal method. We found that ß-NaGdF4:0.25Eu3+ and ß-NaGdF4:0.25Eu3+,0.005Yb3+ phosphors possess ZTQ properties at a temperature range between 303-483 K and 303-523 K, respectively. The thermoluminescence (TL) spectra were employed to calculate the depth and density of the VNa vacancies in ß-NaGdF4:0.25Eu3+ and ß-NaGdF4:0.25Eu3+,0.005Yb3+. Combining the DFT calculation with characterization results of TL spectra, it is concluded that electrons stored in VNa vacancies are excited to the exited state of Eu3+ to compensate for the loss of Eu3+ luminescent intensity. This will lead to an increase of luminescent intensity at high temperatures and facilitate the samples to improve ZTQ properties. WLEDs were obtained with CRI = 83.0, 81.6 and CCT = 5393, 5149 K, respectively, when phosphors of ß-NaGdF4:0.25Eu3+ and ß-NaGdF4:0.25Eu3+,0.005Yb3+ were utilized as the red-light source. These results indicate that these two phosphors may become reliable red-light sources with high antithermal quenching properties for WLEDs.

Amide proton transfer imaging has added value for predicting extraprostatic extension in prostate cancer patients.

Background: Prostate cancer invades the capsule is a key factor in selecting appropriate treatment methods. Accurate preoperative prediction of extraprostatic extension (EPE) can help achieve precise selection of treatment plans. Purpose: The aim of this study is to verify the diagnostic efficacy of tumor size, length of capsular contact (LCC), apparent diffusion coefficient (ADC), and Amide proton transfer (APT) value in predicting EPE. Additionally, the study aims to investigate the potential additional value of APT for predicting EPE. Method: This study include 47 tumor organ confined patients (age, 64.16 ± 9.18) and 50 EPE patients (age, 61.51 ± 8.82). The difference of tumor size, LCC, ADC and APT value between groups were compared. Binary logistic regression was used to screen the EPE predictors. The receiver operator characteristic curve analysis was performed to assess the diagnostic performance of variables for predicting EPE. The diagnostic efficacy of combined models (model I: ADC+LCC+tumor size; model II: APT+LCC+tumor size; and model III: APT +ADC+LCC+tumor size) were also analyzed. Results: APT, ADC, tumor size and the LCC were independent predictors of EPE. The area under the curve (AUC) of APT, ADC, tumor size and the LCC were 0.752, 0.665, 0.700 and 0.756, respectively. The AUC of model I, model II, and model III were 0.803, 0.845 and 0.869, respectively. The cutoff value of APT, ADC, tumor size and the LCC were 3.65%, 0.97×10-3mm2/s, 17.30mm and 10.78mm, respectively. The sensitivity/specificity of APT, ADC, tumor size and the LCC were 76%/89.4.0%, 80%/59.6%, 54%/78.9%, 72%/66%, respectively. The sensitivity/specificity of model I, Model II and Model III were 74%/72.3%, 82%/72.5% and 84%/80.9%, respectively. Data conclusion: Amide proton transfer imaging has added value for predicting EPE. The combination model of APT balanced the sensitivity and specificity.

Long-Term Follow-Up of Ultrasound-Guided Glossopharyngeal Nerve Block Treatment for Glossopharyngeal Neuralgia: A Retrospective Clinical Study of 43 Cases.

Background: Glossopharyngeal neuralgia (GPN) is a rare chronic neuropathic pain disorder that significantly impacts quality of life. Ultrasound-guided glossopharyngeal nerve blocks (UGPNB) have gained popularity due to their various advantages. However, there have been no studies reporting the long-term outcomes of UGPNB in a larger cohort of GPN patients. Aim: This study aims to evaluate the efficacy and safety of UGPNB in patients with GPN. Methods: We reviewed the electronic medical records of patients with GPN who received UGPNB at the Department of Pain Medicine of the First Medical Center, PLA General Hospital between June 1, 2011, and June 1, 2022. The effect of UGPNB was evaluated using the Barrow Neurological Institute (BNI) scale. Improvement was defined as a reduction in pain category by comparing pain categories before and after therapy. Recovery was defined as achieving BNI I after treatment. Patients who responded to treatment but then regressed to the category before therapy were considered to have experienced pain relapse. Results: A total of 43 patients with GPN who received UGPNB were included in the analysis. At discharge, 35 (81.4%) patients experienced pain improvement after treatment, and among them, 13 (30.2%) patients achieved recovery. After discharge, 13 patients (37.1%) out of the 35 effective patients experienced pain relapse at different time intervals: 0.5, 0.7, 1, 1, 3, 3, 4, 12, 15, 36, 45, 63, and 96 months. The cumulative recurrence-free survival rates were 88.85% at month 1, 82.83% at month 3, 77.04% at month 12, 70.31% at month 36, and 54.66% at month 120. Among the 13 patients who experienced relapse, four patients received a second UGPNB treatment, and pain improved in two patients (50%). No severe adverse reactions were documented. Conclusion: UGPNB is an effective, repeatable, safe, and minimally invasive treatment for patients with GPN. It may be preferable to consider UGPNB before undergoing invasive intracranial surgery or neurodestructive methods.

Hippocampal amide proton transfer values are associated with cerebral small vessel disease imaging markers and total burden: a community-based cross-sectional study.

Background: Neurodegeneration has been suggested to be associated with cerebral small vessel disease (CSVD). The association between different CSVD imaging markers and the extent of neurodegeneration could be indirectly confirmed by examining the relationship between CSVD imaging markers and the hippocampal amide proton transfer (APT) values. The associations between hippocampal APT values with CSVD imaging markers and CSVD total load need to be further validated. The aim of this study was to investigate potential variations in hippocampal APT values among individuals with CSVD imaging markers and varying degrees of CSVD total burden. Methods: A cross-sectional study (retrospective analysis of prospectively-acquired data) was conducted at Nanxishan Hospital of Guangxi Zhuang Autonomous Region. From May 2020 to June 2021, 165 individuals (age, 40-76 years; male/female, 103/62) were included in this study. The inclusion criteria for the participants were as follows: The presence of lacunar infarction (LI), and/or cerebral microbleed (CMB); moderate-to-severe enlarged perivascular space (EPVS) (>20); deep white matter hyperintensity (WMH) > Fazekas 2 or periventricular WMH > Fazekas. The exclusion criteria comprised the following: History of craniocerebral operation; Cases with significant pathology incidentally identified during magnetic resonance (MR) scan; Drug or alcohol abuse. The differences of hippocampal APT values between CSVD imaging makers presence or absence groups and different CSVD total burden groups were compared using independent t-test and one-way analysis of variance (ANOVA). The correlations between APT values and CSVD imaging markers were analyzed using Pearson correlation analysis. A mediation analysis model was used to investigate the mediating effect of the hippocampal APT values in the association between CSVD total loads and Montreal Cognitive Assessment (MoCA) score was assessed. Results: The hippocampal APT values among different CSVD total load groups were significantly different (P<0.001). The hippocampal APT values were significantly different between the imaging markers presence and absence groups. The P values for the LI, WMH EPVS, and CMB presence or absence groups were <0.001, <0.001, 0.034, and 0.002, respectively. The hippocampal APT values were significantly correlated with CMB (P<0.01), LI (P<0.01) and WMH (P<0.01). The mediation models demonstrated that the APT values of the hippocampus partially mediated the association between CSVD total load and MoCA score, the proportion of mediation attributable was calculated as 17.50%. Conclusions: Hippocampal APT values were associated with CSVD imaging markers and total burden. Hippocampal APT values may serve as a biomarker for the early detection of neurodegeneration in CSVD patients.

Ano1 regulates embryo transport by modulating intracellular calcium levels in oviduct smooth muscle.

Oviductal smooth muscle exhibits spontaneous rhythmic contraction (SRC) and controls the passage of the ova at the exact time, but its mechanistic regulation remains to be determined. In this study, female mice with Ano1SMKO (smooth muscle-specific deletion of Ano1) had reduced fertility. Deficiency of Ano1 in mice resulted in impaired oviductal SRC function and reduced calcium signaling in individual smooth muscle cells in the oviduct. The Ano1 antagonist T16Ainh-A01 dose-dependently inhibited SRCs and [Ca2+]i in the oviducts of humans and mice. A similar inhibitory effect of SRCs and [Ca2+]i was observed after treatment with nifedipine. In our study, ANO1 acted primarily as an activator or amplifier in [Ca2+]i and contraction of tubal smooth muscle cells. We found that tubal SRC was markedly attenuated in patients with ectopic pregnancy. Then, our study was designed to determine whether chloride channel Ano1-mediated smooth muscle motility is associated with tubal SRC. Our findings reveal a new mechanism for the regulation of tubal motility that may be associated with abnormal pregnancies such as ectopic pregnancies.

Platelet-Derived Growth Factor Nanocapsules with Tunable Controlled Release for Chronic Wound Healing.

Chronic wounds have emerged as an increasingly critical clinical challenge over the past few decades, due to their increasing incidence and socioeconomic burdens. Platelet-derived growth factor (PDGF) plays a pivotal role in regulating processes such as fibroblast migration, proliferation, and vascular formation during the wound healing process. The delivery of PDGF offers great potential for expediting the healing of chronic wounds. However, the clinical effectiveness of PDGF in chronic wound healing is significantly hampered by its inability to maintain a stable concentration at the wound site over an extended period. In this study, a controlled PDGF delivery system based on nanocapsules is proposed. In this system, PDGF is encapsulated within a degradable polymer shell. The release rate of PDGF from these nanocapsules can be precisely adjusted by controlling the ratios of two crosslinkers with different degradation rates within the shells. As demonstrated in a diabetic wound model, improved therapeutic outcomes with PDGF nanocapsules (nPDGF) treatment are observed. This research introduces a novel PDGF delivery platform that holds promise for enhancing the effectiveness of chronic wound healing.

Amide proton transfer could be a surrogate imaging marker for predicting vascular cognitive impairment.

BACKGROUD: Emerging evidence suggests an overlap in the underlying pathways contributing to both cerebral small vessel disease (CSVD) and the neurodegenerative disease. Studies investigating the progression of CSVD should incorporate markers that reflect neurodegenerative lesions. OBJECTIVE: We aim to investigate whether Amide proton transfer (APT) can serve as a potential marker for reflecting vascular cognitive impairment (VCI). METHOD: Participants were categorized into one of three groups based on their Montreal Cognitive Assessment (MoCA) scores: normal control group (age,54.9 ± 7.9; male, 52.9%), mild cognitive impairment (MCI) group (age,55.7 ± 6.9; male, 42.6%), or vascular dementia (VaD) group (age,57.6 ± 5.5, male, 58.5%). One way analysis of variance was performed to compare the demographic and APT variables between groups. Multiple logistic regression analysis wwas constructed to examine the relationship between APT values and VCI grouping. A hierarchical linear regression model was employed to examine the associations between patients' demographic factors, imaging markers, APT values, and MoCA. RESULTS: The APT values of frontal white matter, hippocampus, amygdala, and thalamus were significantly different among different groups (p < 0.05). The APT values of frontal white matter, amygdala, and thalamus indicate a significant positive effect on MCI grouping. the APT values of frontal white matter, amygdala, and thalamus indicate a significant positive effect on VaD grouping. The demographic data, CSVD imaging markers and APT values can account for 5.1%, 20.1% and 27.7% of the variation in MoCA, respectively. CONCLUSION: APT imaging can partially identifying and predicting the occurrence of VCI.

Spectral computed tomography parameters could be surrogate imaging markers to detect early perfusion changes in diabetic kidneys.

Background: Kidney microvasculopathy is the baseline pathophysiological feature of diabetic kidney disease (DKD). We aimed to evaluate the spectral computed tomography (CT) parameters for detecting renal perfusion changes among diabetic patients. Methods: From August 2020 to June 2022, 34 patients (age, 57.7±10.7 years; male, 20) clinically diagnosed with type 2 diabetes mellitus (DM) and 19 DM-free individuals (age, 48.1±16.9 years; male, 12) were selected for analysis. The series participants formed the DM group and control group, respectively. Spectral parameters, including effective atomic number (Zeff), iodine density (ID), normalized iodine density (NID) and the slope of the energy spectrum curves (λ), between the 2 groups were analyzed using independent samples t-test. Receiver operator characteristic (ROC) curves were used to evaluate the diagnostic performance of spectral parameters for detecting renal perfusion changes. Results: The results indicate that in both cortical and medullary phases, the values of Zeff, ID, NID, and λ40-70 for the renal cortex of the DM group were significantly higher than those in the control group (P<0.05). In the cortex phase, the diagnostic efficacy of cortical spectral CT parameters discriminating DM patients from controls was as follows: the area under ROC curve (AUC) of ID value was 0.816 [95% confidence interval (CI): 0.679-0.921] at the optimal cutoff value 4.14, the AUC of Zeff value was 0.800 (95% CI: 0.668-0.901) at the optimal cutoff value 9.26, the AUC of λ40-70 value was 0.822 (95% CI: 0.675-0.918) at the optimal cutoff value 8.26, and the AUC of NID value was 0.851 (95% CI: 0.684-0.926) at the optimal cutoff value 0.37. In medullary phase: the AUC of ID value was 0.769 (95% CI: 0.617-0.846) at the optimal cutoff value 5.08, the AUC of Zeff value was 0.763 (95% CI: 0.614-0.837) at the optimal cutoff value 9.58, the AUC of λ40-70 value was 0.766 (95% CI: 0.617-0.839) at the optimal cutoff value 10.07, and the AUC of NID value was 0.79 (95% CI: 0.623-0.855) at the optimal cutoff value 1.37. Conclusions: Spectral CT could serve as an alternative protocol for the early identification of kidney injury in diabetic patients.

Integrating network pharmacology with molecular docking for elucidation of molecular biological mechanisms of Jiedu Qingjin formula for non-small cell lung cancer.

Traditional Chinese medicine is an important part of complementary alternative medicine. Jiedu Qingjin formula (JDQJF) is an effective national invention patent for the treatment of non-small cell lung cancer (NSCLC). We investigated the molecular biological mechanisms based on network pharmacology, molecular docking, and molecular dynamics simulations. Compounds of JDQJF were screened through the TCMSP, ETCM, and literature. Targets were searched by DrugBank and predicted by SwissTargetPrediction. GEO database was applied for screening differentially expressed genes between cancerous tissues and healthy tissues of NSCLC. Subsequently, the protein-protein interaction between JDQJF and NSCLC were obtained by Cytoscape. Visual analyses were carried out to extract candidate genes, then subjected to Metascape for enrichment analyses. Finally, molecular docking was performed by AutoDock, and the best complexes were subjected to molecular dynamics simulation and binding energy calculations by MMPBSA. A total of 273 compounds, 390 targets, 3146 GO terms, and 174 KEGG pathways were obtained. Five potential compounds (quercetin, adenosine, apigenin, heptadecanoic acid, and luteolin) were notably modulated by key targets AKT1, MAPK3, and RAF1. Enrichment results included cell cycle process, growth transduction factor, immune response-activating transduction, and involved PI3K/AKT, MAPK, NF-κB and VEGF pathway. RAF1-quercetin showed the highest binding affinity (-9.1 kcal/mol), revealed stable interactions during the simulation, and the highest estimated relative binding energy of the RAF1-Heptadecanoic was -184.277 kcal/mol. This study suggested that EMT-related, inflammation-related, immune-related, and angiogenesis-related pathways may be associated with JDQJF, and involved in the advancement of NSCLC, which points out the research direction for subsequent utility mechanism validation.Communicated by Ramaswamy H. Sarma.

Textural features of the frontal white matter could be used to discriminate amnestic mild cognitive impairment patients from the normal population.

OBJECTIVE: We aim to develop a radiomics model based on 3-dimensional (3D)-T1WI images to discriminate amnestic mild cognitive impairment (aMCI) patients from the normal population by measuring changes in frontal white matter. METHODS: In this study, 126 patients with aMCI and 174 normal controls (NC) were recruited from the local community. All subjects underwent routine magnetic resonance imaging examination (including 3D-T1WI ). Participants were randomly divided into a training set (n = 242, aMCI:102, NC:140) and a testing set (n = 58, aMCI:24, NC:34). Texture features of the frontal lobe were extracted from 3D-T1WI images. The least absolute shrinkage and selection operator (LASSO) was used to reduce feature dimensions and develop a radiomics signature model. Diagnostic performance was assessed in the training and testing sets using the receiver operating characteristic (ROC) curve analysis. The area under the ROC curve (AUC), sensitivity, and specificity were also calculated. The efficacy of the radiomics model in discriminating aMCI patients from the normal population was assessed by decision curve analysis (DCA). RESULTS: A total of 108 frontal lobe texture features were extracted from 3D-T1WI images. LASSO selected 58 radiomic features for the final model, including log-sigma (n = 18), original (n = 8), and wavelet (n = 32) features. The performance of radiomic features extracted from 3D T1 imaging for distinguishing aMCI patients from controls was: in the training set, AUC was 1.00, and the accuracy, sensitivity, and specificity were 100%, 98%, and 100%, respectively. In the testing set, AUC was 0.82 (95% CI:0.69-0.95), and the accuracy, sensitivity, and specificity were 69%, 92%, and 55%, respectively. The DCA demonstrated that the model had favorable clinical predictive value. CONCLUSIONS: Textural features of white matter in the frontal lobe showed potential for distinguishing aMCI from the normal population, which could be a surrogate protocol to aid aMCI screening in clinical setting.

Hysteroscopic removal of a heterotopic cervical pregnancy to preserve a patient's intrauterine sac.

OBJECTIVE: To introduce a case of removing heterotopic cervical pregnancy while preserving the normal gestational sac in the uterine cavity by hysteroscopic surgery under ultrasound guidance. DESIGN: Video description of the case and surgical procedure. SETTING: Hospital affiliated to a university. PATIENT: A 35-year-old woman with G7P1A5L1 was admitted with a heterotopic cervical pregnancy 21 days after in vitro fertilization and embryo transfer (the corrected gestational age was 5+2 weeks). The serum ß-human chorionic gonadotropin level was 24,530 mIU/mL at the corrected gestational age of 5+3 weeks. Ultrasound examination on the day of admission showed that there was a gestational sac in the cervical canal (1.5 × 0.8 × 0.5 cm, yolk sac visible) and another in the intrauterine cavity (1.2 × 1.2 × 1.1 cm, yolk sac visible). The pregnant woman and her partner strongly urged to remove the cervical gestational sac and continue the intrauterine pregnancy to term. INTERVENTION: After the Institutional Review Board approval was obtained, hysteroscopic surgery with bipolar resectoscope and transabdominal ultrasound guidance was used to resect the heterotopic cervical pregnancy while preserving the intrauterine gestational sac. MAIN OUTCOME MEASURES: The heterotopic cervical pregnancy was completely resected by hysteroscopy, and the normal gestational sac in the uterine cavity was successfully preserved. RESULTS: Ultrasound-guided hysteroscopic surgery allowed us to successfully preserve the intrauterine pregnancy while removing the cervical pregnancy completely. During the operation, the dilation pressure and the flow rate of the dilation fluid was kept as low as possible to avoid excessive intrauterine pressure and excessive dilation fluid entering the intrauterine cavity, which could have had adverse effects on the intrauterine pregnancy sac. No surgical- or anesthesia-related complications occurred. The pathological results confirmed placental villi and decidual tissue. The one-month follow-up ultrasonography showed a live single intrauterine pregnancy with cardiac activity. CONCLUSION(S): Hysteroscopic removal of a heterotopic cervical pregnancy under ultrasound guidance can be safely performed while successfully preserving an ongoing intrauterine pregnancy.

Safety, Tolerability, and Pharmacokinetics of Recombinant Human Neuregulin-1 in Healthy Chinese Subjects.

BACKGROUND: We investigated the safety, tolerability, and pharmacokinetics of intravenous recombinant human Neuregulin-1 (rhNRG-1), a DNA recombinant protein for the treatment of chronic heart failure, in healthy Chinese volunteers following single and multiple dose administration. METHODS AND RESULTS: To evaluate the safety and tolerance after single-dosing escalation, 28 subjects were divided into six groups (0.2, 0.4, 0.8, 1.2, 1.6, and 2.4 µg/kg) to receive an intravenous (IV) infusion of rhNRG-1 over 10 min by a randomized, open-label design. Only the 1.2 µg/kg dose group obtained pharmacokinetic parameters: Cmax was 7.645 (24.21) ng/mL, AUC0-t was 97.088 (21.41) min·ng/mL. To assess the safety and pharmacokinetics after multiple-dosing, 32 subjects were divided into four groups (0.2, 0.4, 0.8, and 1.2 µg/kg) to receive a 10-min IV infusion of rhNRG-1 for five consecutive days. After multiple dosing of 1.2 µg/kg, the Cmax value at day 5 was 8.838 (51.6) ng/mL and the AUC0-t value at day 5 was 109.890 (32.99) min·ng/mL. RhNRG-1 is rapidly cleared from the blood and has a short t1/2 of about 10 min. The adverse events related to rhNRG-1 mainly included flat or inverted T wave and gastrointestinal reactions, all of which were mild. CONCLUSIONS: It is concluded that rhNRG-1 is safe and well tolerated in healthy Chinese subjects at the dosing levels used in this study. The severity and frequency of adverse events did not increase with the prolongation of administration time. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry ( http://www.chictr.org.cn ) Identifier No. ChiCTR2000041107.

Preparation of a Transient Thermal Expansion Rock Cracking Agent by Deposition Method and Its Nonisothermal Kinetics Study with Isoconversional Procedure and DAEM.

Cracking agents are indispensable and important products for national energy exploitation and large-scale infrastructure construction. Transient thermal expansion rock cracking agent is a new cracking agent product with excellent performance that has just appeared in recent years. However, it is still prepared by mechanical ball milling, which is considered not the best choice among traditional methods for preparing energetic materials. In this paper, a transient thermal expansion rock splitting agent was prepared by the chemical deposition method using carbon black and calcium peroxide as raw materials. The TG/DTG results show that the mass loss of the sample can be divided into four stages with the increase of temperature. It is worth noting that the mass loss of the TG curve of the sample during the entire thermal decomposition process is 93.385%, and the instantaneous weight loss is 78.07% (ß = 15 °C/min). Kinetic analysis of the thermal decomposition process of the samples was performed using an isotransformation program and a distributed activation energy model (DAEM). The activation energy E α of the thermal decomposition of the sample was iteratively calculated. The results show that the a-E a curve of the sample can be divided into two stages. The pyrolysis kinetics of the first stage was successfully analyzed by the DAEM method and its thermal conversion behavior was predicted. The thermal decomposition behavior of the second stage was analyzed by a traditional kinetic analysis method.

Challenges of EGFR-TKIs in NSCLC and the potential role of herbs and active compounds: From mechanism to clinical practice.

Epidermal growth factor receptor (EGFR) mutations are the most common oncogenic driver in non-small cell lung cancer (NSCLC). Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are widely used in the treatment of lung cancer, especially in the first-line treatment of advanced NSCLC, and EGFR-TKIs monotherapy has achieved better efficacy and tolerability compared with standard chemotherapy. However, acquired resistance to EGFR-TKIs and associated adverse events pose a significant obstacle to targeted lung cancer therapy. Therefore, there is an urgent need to seek effective interventions to overcome these limitations. Natural medicines have shown potential therapeutic advantages in reversing acquired resistance to EGFR-TKIs and reducing adverse events, bringing new options and directions for EGFR-TKIs combination therapy. In this paper, we systematically demonstrated the resistance mechanism of EGFR-TKIs, the clinical strategy of each generation of EGFR-TKIs in the synergistic treatment of NSCLC, the treatment-related adverse events of EGFR-TKIs, and the potential role of traditional Chinese medicine in overcoming the resistance and adverse reactions of EGFR-TKIs. Herbs and active compounds have the potential to act synergistically through multiple pathways and multiple mechanisms of overall regulation, combined with targeted therapy, and are expected to be an innovative model for NSCLC treatment.

Functional chitosan gel coating enhances antimicrobial properties and osteogenesis of titanium alloy under persistent chronic inflammation.

Titanium is widely used as surgical bone implants due to its excellent mechanical properties, corrosion resistance, and good biocompatibility. However, due to chronic inflammation and bacterial infections caused by titanium implants, they are still at risk of failure in interfacial integration of bone implants, severely limiting their broad clinical application. In this work, chitosan gels crosslinked with glutaraldehyde were prepared and successfully loaded with silver nanoparticles (nAg) and catalase nanocapsules (n (CAT)) to achieve functionalized coating on the surface of titanium alloy steel plates. Under chronic inflammatory conditions, n (CAT) significantly reduced the expression of macrophage tumor necrosis factor (TNF-α), increased the expression of osteoblast alkaline phosphatase (ALP) and osteopontin (OPN), and enhanced osteogenesis. At the same time, nAg inhibited the growth of S. aureus and E. coli. This work provides a general approach to functional coating of titanium alloy implants and other scaffolding materials.

Regulation of bone and fat balance by Fructus Ligustri Lucidi in ovariectomized mice.

CONTEXT: Fructus Ligustri Lucidi (FLL), a commonly used herb of traditional Chinese medicine (TCM), is the fruit of Ligustrum lucidum Ait. (Oleaceae). The ethanol extract of FLL is a potential candidate for preventing and treating postmenopausal osteoporosis (PMOP) by nourishing the liver and kidneys. OBJECTIVE: This study determines whether an ethanol extract of FLL has anti-osteoporotic effects in ovariectomized (OVX) mice and explores the underlying mechanism. MATERIALS AND METHODS: The OVX model of eight-week-old C57BL/6J female mice was taken, and ovariectomy was used as PMOP. Mice were divided into five groups: sham-operated group (n = 10), OVX group (n = 10), OVX + E2 group (n = 10; 0.039 mg/kg), OVX + FLL group (n = 10; 2 g/kg) and OVX + FLL group (n = 10; 4 g/kg). Mice were treated by gavage with FLL or CMCNa once daily for 8 weeks. We harvested uteri, femur, and tibias from mice; bone mineral density (BMD) and bone microstructure were obtained by X-ray absorptiometry and micro-CT. Furthermore, the effect of FLL on the balance of osteoblast and adipocyte differentiation was investigated using bone marrow mesenchymal stem cells (BMMSCs). RESULTS: The results indicated that FLL did not affect OVX-induced estradiol reduction. Compared with OVX mice, FLL significantly increased BMD (63.54 vs. 61.96), Conn. D (86.46 vs. 57.00), and left tibial strength (13.91 vs. 11.27), decreased Tb. Sp (0.38 vs. 0.44) and body fat content (4.19% vs. 11.24%). FLL decreased osteoclast activity and enhanced RUNX2 expression; inhibited perilipin peroxisome proliferator-activated receptor gamma (PPARγ) expression and adipocyte differentiation from BMMSCs. CONCLUSIONS: FLL prevented additional bone loss and improved bone microstructure in OVX mice by modulating bone and fat balance, suggesting that FLL might be a therapeutic agent for PMOP.