Hydrochloride Injection Research Articles

Liposomal Bupivacaine Does Not Decrease Postoperative Pain in Patients with Intracapsular Femoral Neck Fracture Treated with Hemiarthroplasty: HEAT-A Randomized, Controlled Trial.

Liposomal bupivacaine (LB) is a long-lasting local anesthetic agent that was developed for use in the surgical setting to help manage postoperative pain. The objective of this study was to evaluate the effect of LB on postoperative pain, function, and overall hospital course in patients with intracapsular hip fractures who were treated with hip hemiarthroplasty. This was a single-center, randomized prospective double-blinded study of 50 patients with an isolated intracapsular femoral neck fracture who were treated with hip hemiarthroplasty from 2018 to 2022. The study group consisted of 25 patients who were treated with intraoperative LB and bupivacaine hydrochloride injections, while the control group consisted of 25 patients who were treated with intraoperative bupivacaine hydrochloride injections only. Primary outcomes were a visual analog scale (VAS) score for pain, total morphine milligram equivalents (MME), delirium, and time to ambulation with physical therapy. No significant differences between the study and control groups were found in any of the outcomes measured. Most notably, there were no differences in the average postoperative pain score (VAS, 2.26 versus 2.7; p = 0.34), total MME used postoperatively (11.73 versus 9.98 MME; p = 0.71), and postoperative day of discharge (4.00 versus 3.88 days; p = 0.82). The results of our study suggest that use of LB is not associated with substantially improved postoperative pain or function or with a shorter hospital course following hip hemiarthroplasty for a femoral neck fracture. Given the higher cost of LB compared with standard postoperative pain modalities, it is worth questioning its use in the setting of geriatric hip fractures. Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Tet1-mediated activation of the Ampk signaling by Trpv1 DNA hydroxymethylation exerts neuroprotective effects in a rat model of Parkinson's disease.

Epigenetic regulation plays a role in Parkinson's disease (PD), and ten-eleven translocation methylcytosine dioxygenase 1 (TET1) catalyzes the first step in DNA demethylation by converting 5-methylcytosine to 5-hydroxymethylcytosine. We investigated whether TET1 binds to the promoter of the transient receptor potential cation channel subfamily V member 1 (TRPV1) and regulates its expression, thereby controlling oxidative stress in PD. TRPV1 was identified as an oxidative stress-associated gene in the GSE20186 dataset including substantia nigra from 14 patients with PD and 14 healthy controls and the Genecards database. Lentiviral vectors were used to manipulate Trpv1 expression in rats, followed by 6-hydroxydopamine hydrochloride (6-OHDA) injection for modeling. Behavioral tests, immunofluorescence, Nissl staining, western blot assays, DHE fluorescent probe, biochemical analysis, and ELISA were conducted to assess oxidative stress and neurotoxicity. Trpv1 expression was significantly reduced in the brain tissues of 6-OHDA-treated Parkinsonian rats. Trpv1 alleviated behavioral dysfunction, oxidative stress, and dopamine neuron loss in rats. TET1 mediated TRPV1 hydroxymethylation to promote its expression, and Trpv1 inhibition reversed the mitigating effect of Tet1 on oxidative stress and behavioral dysfunction in PD. TRPV1 activated the AMPK signaling by promoting AMPK phosphorylation to alleviate neurotoxicity and oxidative stress in SH-SY5Y cells. Tet1-mediated Trpv1 hydroxymethylation modification promotes the Ampk signaling activation, thereby eliciting neuroprotection in 6-OHDA-treated Parkinsonian rats. These findings provide experimental evidence that targeting the TET1/TRPV1 axis may be neuroprotective for PD by acting on the AMPK signaling.

The Effect of Gold Nanoparticles and Apricot Kernel Extract on the Osseointegration of Dental Implants - A Rabbit Model

Introduction The osseointegration of dental implants is critical to their longevity and success. Various factors such as surface modifications, both additive and subtractive, systemic drug administration, growth factors, and plasma derivatives can influence osseointegration. Aims and Objectives This study aimed to study the effects of gold nanoparticles and aqueous extract of apricot kernels on the osseointegration of titanium implants in the tibia of rabbits. Materials and Methods Apricot kernels were dried, grounded, and dissolved in water to obtain an aqueous extract. It was filtered and stored in the refrigerator at 4oC. Gold nanoparticles (AuNPs) were prepared by mixing 3 ml of 0.02 mM hydrogen tetrachloroaurate with 1 ml of olive leaf extract. The mixture was stirred vigorously for 15 minutes on a heater stirrer at 50oC. Titanium screw implants were sterilized in an autoclave at 120oC with 15 pounds per square inch for 30 minutes. Sterilized implants were stored in sealed containers until use. The study was carried out at the College of Veterinary Medicine, University of Mosul, Iraq. The ethical approval for the study was obtained from the institutional animal care and use committee, College of Veterinary Medicine, University of Mosul, Mosul, Iraq, on 15/04/2023 on reference no UM.VET.2023.013. Nine healthy male adult white New Zealand rabbits aged between 10-12 months were utilized for the study. Three pure titanium implants, each of a type, were placed in each tibia. The implants were categorized as follows: control group (18 uncoated implants) and experimental group (36 coated implants). The implant placement was divided into three groups: controls with uncoated implants (n=18), AuNPs-coated implants (n=18), and apricot kernel extract-coated implants (n=18). General anesthesia was induced by intramuscular injection of ketamine hydrochloride 50mg (1ml /kg of body weight) plus xylazine 2% (0.2 ml /kg of body weight). The AuNPs-coated implants were implanted in the superior osteotomy site in the tibia. The apricot kernel extract-coated implants were implanted in the inferior osteotomy site and the uncoated implants were implanted in the middle osteotomy sites. Histological and histomorphometric tests were performed on all bone implant blocks at one-week, two-week, and three-week intervals after implant placement. The results were evaluated based on the amount of bone formation, cellular components, and inflammation. Tabulated data were statistically analyzed using SPSS v23.0 (IBM, Armonk, NY) using ANOVA with a statistical significance of p <0.05 Results We observed a significant amount of osteogenesis with reduced inflammation in AuNPs-coated implants and apricot kernel extract-coated implants compared to untreated implants. The osteoclastic activity was significantly higher in untreated implants than the treated implant sites. A statistically significant association was observed between coated implants and untreated implants. Conclusion The application of gold nanoparticles and aqueous extract of apricot kernels appears to be promising in reducing inflammation and improving bone apposition on the titanium implant surface. However, this preliminary investigation warrants further research.

Comparison of analgesic effect of modified superior trunk block and traditional interscalene brachial plexus block with liposomal bupivacaine after arthroscopic rotator cuff repair

Objective: To compare the postoperative analgesic effect of modified superior trunk block and traditional interscalene brachial plexus block in arthroscopic rotator cuff repair. Methods: A total of 40 patients undergoing arthroscopic rotator cuff repair in the Second Affiliated Hospital of Wenzhou Medical University from October to November 2023 were prospectively included, whose American Society of Anesthesiologists (ASA) grade were Ⅰ-Ⅱ. They were divided into modified superior trunk block group (group S) and interscalene brachial plexus block group (group I) by random number table according to different nerve block methods, with 20 cases in each group. Local anesthetics was a mixture of 1.33% liposomal bupivacaine and 0.5% levobupivacaine hydrochloride injection in equal volume. Patients in group S were injected 5 ml mixture for ultrasound-guided modified superior trunk block, and patients in group I were injected with 15 ml mixture for ultrasound-guided traditional interscalene block respectively. Both groups underwent superficial cervical plexus block (5 ml mixture). Standardized general anesthesia and standardized postoperative analgesia were followed. The primary outcome measures included 48 h resting numerical rating scale (NRS) scores after surgery and the incidence of hemidiaphragmatic paralysis (HDP) at 30 min after block. The secondary outcome measures included resting NRS scores during the post anesthesia care unit (PACU), 12, 24, and 36 h after surgery, postoperative opioid consumption and satisfaction with analgesia, pulse oxygen saturation (SpO2) at 30 min after block, sensory and motor block duration, and the incidence of perioperative adverse reactions. The non-inferiority cut-off value of resting NRS scores for patients in group S was set as"1 point"at each observation time point after surgery. Results: In group S, one patient was excluded because the target nerve was blocked by the subclavian vein and could not be blocked, nineteen patients [11 males and 8 females, aged (52.2±9.0) years] were eventually included. In group I, there were 7 males and 13 females, aged (55.0±5.1) years. Resting NRS scores of group S and Group I at 48 h after surgery were 0 (0, 0) and 0 (0, 0.8) point, respectively, with no statistical significance (P>0.05). The median difference was 0 (95%CI:0-0) point and the upper 95%CI was 0 point, which was lower than the preset non-inferiority cut-off value"1 point"(non-inferiority P<0.001). The incidence of HDP in group S and group I were 5% (1/19) and 75% (15/20), respectively, with statistically significant (P<0.001). There were no significant differences in resting NRS scores at PACU and 12, 24, 36 h after surgery, opioid dosage, satisfaction with analgesia, SpO2 at 30 min after block, sensory and motor block duration between two groups (all P>0.05). No respiratory adverse events such as hypoxemia and airway spasm occurred in two groups after extubation. One patient in group I showed symptoms of breath shortness when entering PACU, and 3 patients felt uncomfortable due to prolonged numbness and weakness of the blockade limb (>2 days). No nerve block procedures and opioid drugs relative adverse reactions and no neurological complications happened in both groups. Conclusion: Liposomal bupivacaine usage for modified superior trunk block can provide long-term postoperative analgesic effects which is noninferior to traditional interscalene brachial plexus block and causes less HDP in patients undergoing arthroscopic rotator cuff repair.

A Rare Complication in the Oral Local Infiltration Anesthesia.

The present report describes a rare complication named Kuhn anemia, which happened during local infiltration anesthesia of maxillary wisdom tooth. A 24-year-old male was referred for residual crown of left maxillary wisdom tooth and therefore required extraction. Oral examination revealed a buccal impacted left maxillary wisdom tooth (28), severe caries affecting the dental pulp, and pain with percussion. This case was diagnosed as impacted wisdom tooth 28 and pulpitis. Thus, the authors performed an extraction of the 28. After injection of articaine hydrochloride (68mg:1.7mL) containing epinephrine (1:100,000) as local anesthetic, the patient felt pain and heat in the left cheek, and an irregularly shaped pale area appeared on the left cheek. The authors stopped the surgery and comforted him. After a 30-minute break, the cheek turned normal, and abnormal sensation was no longer felt.

Symptomatic hepatic cyst treated with endoscopic ultrasound-guided drainage and minocycline hydrochloride injection: a case report.

A 72year-old male patient with a history of a hepatic cyst presented to our hospital with epigastric pain. The cyst had enlarged to approximately 130mm and was diagnosed as a symptomatic hepatic cyst. Percutaneous cyst drainage was deemed challenging because of the risk of intestinal perforation; therefore, transgastric endoscopic ultrasound-guided hepatic cyst drainage was performed with external nasal cyst drainage. After cyst shrinkage was confirmed, minocycline hydrochloride was injected into the cyst through the nasal drainage tube, and the nasal cyst drainage was removed. Nine months after treatment, the cyst diameter markedly reduced to 12mm on computed tomography, and the symptoms improved. In cases where surgery is complex or it is difficult to secure a percutaneous puncture line, endoscopic ultrasound-guided drainage and minocycline hydrochloride injection may be effective if a puncture route can be secured under endoscopic ultrasound.

Augmentation of functional recovery via ROCK/PI3K/AKT pathway by Fasudil Hydrochloride in a rat sciatic nerve transection model

BackgroundsThe functional recovery after peripheral nerve injury remains unsatisfactory. This study aims to perform a comprehensive evaluation of the efficacy of Fasudil Hydrochloride at treating the sciatic nerve transection injury in rats and the mechanism involved. Materials and methodsIn animal experiments, 75 Sprague Dawley rats that underwent transection and repair of the right sciatic nerve were divided into a control, Fasudil, and Fas + LY group, receiving daily intraperitoneal injection of saline, Fasudil Hydrochloride (10 mg/kg), and Fasudil Hydrochloride plus LY294002 (5 mg/kg), respectively. At day 3 after surgery, the expression of ROCK2, p-PI3K, and p-AKT in L4-5 DRG and the lumbosacral enlargement was determined using Western blotting. At day 7 and 14, axon density in the distal stump was evaluated with immunostaining using the anti-Neurofilament-200 antibody. At day 30, retrograde tracing by injecting Fluoro-gold in the distal stump was performed. Three months after surgery, remyelination was analyzed with immostaining using the anti-MPZ antibody and the transmission electron microscope; Moreover, Motion-Evoked Potential, and recovery of sensorimotor functions was evaluated with a neuromonitor, Footprint, Hot Plate and Von Frey Filaments, respectively. Moveover, the Gastrocnemius muscles were weighed, and then underwent H＆E staining, and staining of the neuromuscular junction using α-Bungarotoxin to evaluate the extent of atrophy and degeneration of the endplates in the Gastrocnemius. In vitro, spinal motor neurons (SMNs) and dorsal root ganglia (DRG) were cultured to examine the impact of Fasudil Hydrochloride and LY294002 on the axon outgrowth. ResultsThree days after injury, the expression of ROCK2 increased significantly (P＜0.01), and Fasudil application significantly increased the expression of p-PI3K and p-AKT in L4-6 DRG and the lumbosacral enlargement (P < 0.05). At day 7 and 14 after surgery, a higher axon density could be observed in the Fasudil group(P < 0.05). At day 30 after surgery, a larger number of motor and sensory neurons absorbing Fluoro-gold could be observed in the Fasudil group (P < 0.01) Three months after surgery, a greater thickness of myelin sheath could be observed in the Fasudil group (P < 0.05). The electrophysiological test showed that a larger amplitude of motion-evoked potential could be triggered in the Fasudil group (P < 0.01). Behavioral tests showed that a higher sciatic function index and a lower threshold for reacting to heat and mechanical stimuli could be measured in the Fasudil group. (P < 0.01). The wet weight ratio of the Gastrocnemius muscles and the area of the cross section of its myofibrils were greater in the Fasudil group (P < 0.01), which also demonstrated a higer ratio of axon-endplate connection and a larger size of endplates (P < 0.05). And there were no significant differences for the abovementioned parameters between the control and Fas + LY groups (P＞0.05). In vitro studies showed that Fasudil could significantly promote axon growth in DRG and SMNs, and increase the expression of p-PI3K and p-AKT, which could be abolished by LY294002 (P < 0.05). ConclusionsFasudil can augment axon regeneration and remyelination, and functional recovery after sciatic nerve injury by activating the PI3K/AKT pathway. The translational potential of this articleThe translation potential of this article is that we report for the first time that Fasudil Hydrochloride has a remarkable efficacy at improving axon regeneration and remyelination following a transection injury of the right sciatic nerve in rats through the ROCK/PI3K/AKT pathway, which has a translational potential to be used clinically to treat peripheral nerve injury.

Effect of cuff inflation with lidocaine, saline, and air on tracheal tube cuff pressure during laparoscopic resection of colorectal neoplasms: a randomized clinical trial

BackgroundTracheal tube cuff pressure will increase after pneumoperitoneum when the cuff is inflated with air, high pressure can cause tracheal mucosal damage. This prospective trial aimed to assess if inflating with normal saline or lidocaine can prevent increase of tracheal tube cuff pressure and tracheal mucosal damage in laparoscopic surgeries with general anesthesia. Whether changes of tracheal tube cuff transverse diameter (CD) can predict changes of tracheal tube cuff pressure.MethodsNinety patients scheduled for laparoscopic resection of colorectal neoplasms under general anesthesia were randomly assigned to groups air (A), saline (S) or lidocaine (L). Endotracheal tube cuff was inflated with room-temperature air in group A (n = 30), normal saline in group S (n = 30), 2% lidocaine hydrochloride injection in group L (n = 30). After intubation, tracheal tube cuff pressure was monitored by a calibrated pressure transducers, cuff pressure was adjusted to 25 cmH2O (T0.5). Tracheal tube cuff pressure at 15 min after pneumoperitoneum (T1) and 15 min after exsufflation (T2) were accessed. CD were measured by ultrasound at T0.5 and T1, the ability of ΔCD (T1-0.5) to predict cuff pressure was accessed. Tracheal mucous injury at the end of surgery were also recorded.ResultsTracheal tube cuff pressure had no significant difference among the three groups at T1 and T2. ΔCD had prediction value (AUC: 0.92 [95% CI: 0.81–1.02]; sensitivity: 0.99; specificity: 0.82) for cuff pressure. Tracheal mucous injury at the end of surgery were 0 (0, 1.0) in group A, 0 (0, 1.0) in group S, 0 (0, 0) in group L (p = 0.02, group L was lower than group A and S, p = 0.03 and p = 0.04).ConclusionsCompared to inflation with air, normal saline and 2% lidocaine cannot ameliorate the increase of tracheal tube cuff pressure during the pneumoperitoneum period under general anesthesia, but lidocaine can decrease postoperative tracheal mucosa injury. ΔCD measured by ultrasound is a predictor for changes of tracheal tube cuff pressure.Trial registrationChinese Clinical Trial Registry, identifier: ChiCTR2100054089, Date: 08/12/2021.

Effect of electroacupuncture on myocardial transient receptor potential channels in mice with myocardial hypertrophy.

To observe the effect of electroacupuncture (EA) at "Neiguan"(PC6) on cardiac function, cardiac morphology and transient receptor potential channel (TRPC) protein expressions in myocardial tissue of mice with myocardial hypertrophy, so as to explore its mechanisms underlying improvement of myocardial hypertrophy. Forty-five male C57BL/6 mice were randomly divided into control, model and EA groups (15 mice/group). The myocardial hypertrophy model was established by subcutaneous injection of isoproterenol hydrochloride (15 mg·kg-1·d-1) for 14 days. The mice of the control group received subcutaneous injection of same amount of normal saline. The mice of the EA group received EA stimulation (frequency of 2 Hz, intensity of 1 mA) of bilateral PC6 for 20 min each time, once a day for 14 consecutive days. After the intervention, the body weight, tibia length and heart weight were measured. The left ventricular ejection fraction (EF), fractional shortening index (FS), left ventricular end-systolic volume (LVEV), left ventricular end-systolic internal diameter (LVID) and left ventricular posterior wall thickness (LVPW) were measured by using echocardiography for evaluating the cardiac function. The mean number and surface area of myocardial cells was detected by wheat germ agglutinin (WGA) staining, and changes of the cardiac morphology were observed under light microscopy after HE staining. The expression levels of TRPC1, TRPC3, TRPC4 and TRPC6 (TRPC1/3/4/6) in the myocardial tissue were detected by real-time quantitative PCR (qPCR) and Western blot, separately. Compared with the control group, the heart-body weight ratio(P<0.05) and heart-weight-to-tibia-length ratio (P<0.01), LVEV and LVID levels, the relative surface area, left ventricular area ratio, and the expression levels of cardiac TRPC1/3/4/6 were significantly increased (P<0.01, P<0.05), while the EF, FS, LVPW, number of cardiomyocytes, and the left ventricular posterior wall ratio were obviously decreased (P<0.01, P<0.05) in the model group. In comparison with the model group, the heart/body weight ratio, heart-weight-to-tibia-length ratio, LVEV and LVID levels, relative surface area, left ventricular area ratio, and the expression levels of cardiac TRPC1/3/4/6 were significantly decreased (P<0.01, P<0.05), while the EF, FS, LVPW, number of cardiomyocytes and left ventricular posterior wall ratio were significantly increased (P<0.01, P<0.05) in the EA group. H.E. staining showed disordered arrangement of cardiomyocytes and obvious myocardial interstitial inflammatory cell infiltration in the model group, and evident reduction of degree of cardiac fibrosis and interstitial edema in the EA group. EA of PC6 can improve the cardiac function and cardiac morphology in mice with myocardial hypertrophy, which may be related to its functions in down-regulating the expression of transient receptor potential channels.

Method development and validation of Nicardipine Hydrochloride injection and its related substances by RP-HPLC

Method development and validation of Nicardipine Hydrochloride injection and its related substances by RP-HPLC

Prospective,multi-center,and large-scale hospital centralized monitoring of clinical safety of Reduning Injection in 100249 children cases

This study utilized a prospective, large-sample, multi-center, and registered key specialty approach of hospitals to monitor the application of Reduning Injection. A total of 100 249 adolescent patients aged 14 years and below who received Reduning Injection were monitored, resulting in 83 cases of adverse events, with 76 of them being classified as adverse drug reaction(ADR). The calculated incidence rate of ADR for Reduning Injection was 0.076%, indicating a very rare ADR. The main symptoms of ADR were pruritus, diarrhea, abdominal pain, vomiting, high fever, dyspnea, convulsion, and chills. All ADR cases were reported for the first time, including three new ADR cases and 73 known ADR cases. The categories of ADR was general ADR. All ADR was mild in severity. There were more males than females in ADR patients. One patient had a history of ADR, and the drug causing ADR was buprofen. The largest number of ADR cases occurred when the dosage of Reduning injection was 5-10 mL. The dropping speed was 30 drops or less per min, and the solvent type was 5% glucose injection. The most common manifestation of ADR patients was pruritus, followed by diarrhea, abdominal pain, vomiting, high fever, dyspnea, convulsions, and chills. 72 patients(94.74% of ADR patients) discontinued the drug, and three patients(3.95% of ADR patients) were given oxygen inhalation. 47 cases(61.84% of ADR patients) were treated with medication, of which dexamethasone was the most used(24 cases, 46.15% of ADR patients). 76 ADR patients were cured or improved. ADRs are more likely to occur when diagnosed with acute bronchitis by western medicine and cough by traditional Chinese medicine(TCM), TCM syndrome type is wind heat syndrome, and the combination medicine is ambroxol hydrochloride and bromhexine hydrochloride injection, ascorbic acid/vitamin C injection. This result provides an evidence-based safety basis for active pharmacovigilance of Reduning Injection in adolescents aged 14 years and below.

Continuous blood exchange in rats as a novel approach for experimental investigation

Blood exchange therapy, specifically Whole blood exchange (WBE), is increasingly being utilized in clinical settings to effectively treat a range of diseases. Consequently, there is an urgent requirement to establish convenient and clinically applicable animal models that can facilitate the exploration of blood exchange therapy mechanisms. Our study conducted continuous WBE in rats through femoral and tail vein catheterization using dual-directional syringe pumps. To demonstrate the applicability of continuous WBE, drug-induced hemolytic anemia (DIHA) was induced through phenylhydrazine hydrochloride (PHZ) injection. Notability, the rats of DIHA + WBE group all survived and recovered within the subsequent period. After the implementation of continuous WBE therapy day (Day 1), the DIHA + WBE group exhibited a statistically significant increase in red blood cells (RBC) (P = 0.0343) and hemoglobin (HGB) levels (P = 0.0090) compared to DIHA group. The rats in the DIHA + WBE group exhibited a faster recovery rate compared to the DIHA group, indicating the successful establishment of a continuous blood exchange protocol. This experimental approach demonstrates not just promising efficacy in the treatment of DIHA and offers a valuable tool for investigating the underlying mechanisms of blood exchange. Furthermore, it has a great potential to the advancement of biomedical research such as drug delivery exploration.

Comparative efficacy of sweated and non-sweated Salvia miltiorrhiza Bge. extracts on acute myocardial ischemia via regulating the PPARα/RXRα/NF-κB signaling pathway

Salvia miltiorrhiza Bge. (S. miltiorrhiza) is a well-known traditional Chinese medicine for the treatment of cardiovascular diseases. The processing of S. miltiorrhiza requires the raw herbs to sweat first and then dry. The aim of this study was to investigate the anti-acute myocardial ischemia (AMI) of S. miltiorrhiza extracts (including tanshinones and phenolic acids) before and after sweating, and to further explore whether the “sweating” primary processing affected the efficacy of S. miltiorrhiza. The AMI animal model was established by subcutaneous injection of isoprenaline hydrochloride (ISO). After treatment, the cardiac function of rats was evaluated by electrocardiogram (ECG), biochemical, and histochemical analysis. Moreover, the regulation of S. miltiorrhiza extracts on the peroxisome proliferator-activated receptor α (PPARα)/retinoid X receptor α (RXRα)/nuclear transcription factor-kappa B (NF-κB) signaling pathway of rats was assessed by the Western blotting. The results showed that sweated and non-sweated S. miltiorrhiza extracts including tanshinones and phenolic acids significantly reduced ST-segment elevation in ECG and the myocardial infarction area in varying degrees. Meanwhile, sweated and non-sweated S. miltiorrhiza reversed the activities of aspartate transaminase (AST), lactic dehydrogenase (LDH), creatine kinase-MB (CK-MB), and superoxide dismutase (SOD), as well as the levels of interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α) in AMI rats. Concurrently, the results of Western blotting revealed that S. miltiorrhiza extracts regulated the PPARα/RXRα/NF-κB signaling pathway to exert an anti-inflammatory effect. Most importantly, sweated S. miltiorrhiza tanshinones extracts are more effective than the non-sweated S. miltiorrhiza, and the anti-inflammatory efficacy of tanshinones extract was also better than that of phenolic acid extract. Although phenolic acid extracts before and after sweating were effective in anti-AMI, there was no significant difference between them. In conclusion, both tanshinones and phenolic acids extracts of sweated and non-sweated S. miltiorrhiza promote anti-oxidative stress and anti-inflammatory against AMI via regulating the PPARα/RXRα/NF-κB signaling pathway. Further, the comparations between sweated and non-sweated S. miltiorrhiza extracts indicate that sweated S. miltiorrhiza tanshinones extracts have better therapeutic effects on AMI.

A drug–excipient interaction impurity of bromhexine hydrochloride injection: Structure and formation mechanism elucidation

A long-term stability study using high performance liquid chromatography (HPLC) revealed an unidentified impurity in the bromhexine hydrochloride injection, which was employed as a mucolytic agent. Investigations into stress degradation and elemental impurities revealed one of the elemental impurities Fe3+ in this injection as the primary generator of these impurities. This impurity, named N-carboxymethyl bromhexine, was a product formed during drug–excipient interaction between bromhexine and tartaric acid with Fe3+. The structure of the impurity was identified through ultra-high-performance liquid chromatography with diode array detector (UHPLC-DAD), liquid chromatograph mass spectrometer (LC-MS). Further, the formation mechanism of the impurity was discussed. Overall, this study elucidates the cause, origin, and mechanism of an unknown impurity in bromhexine hydrochloride injection, providing a basis for quality control for bromhexine hydrochloride injections and drug products containing both amine and tartaric acid.

A novel copper ion enhanced electrochemical DNA biosensor for the determination of epinephrine

A novel electrochemical biosensor was developed for the detection of epinephrine (EP) by immobilizing double-strand DNA (dsDNA) bound with copper ions on a gold electrode (Cu2+/dsDNA/MCH/AuE). The electrochemical behavior of EP at Cu2+/dsDNA/MCH/AuE was examined, and the results demonstrated a significant enhancement in the electrocatalytic oxidation peak current of EP due to the formation of a stable G-Cu(II)-G sandwich structure between Cu2+ and guanine at the modified electrode. The modification process of the electrode was characterized by scanning electron microscopy, infrared spectroscopy, electrochemical impedance spectroscopy, and differential pulse voltammetry. A study on the effect of pH in phosphate buffer solution on the electrochemical oxidation of EP indicated that the catalytic oxidation process was pH-dependent. A plot of catalytic current versus EP concentration exhibited a dual-linear relationship within two ranges: 1.0–12.5 μM and 12.5–1000.0 μM, with correlation coefficients of 0.995 and 0.997, respectively. The limit of detection was determined to be 47 nM (S/N = 3). According to the calculated Hill coefficient (0.99), it can be concluded that the electrocatalytic process followed the Michaelis-Menten kinetic mechanism. The maximum catalytic current Im was 25 μA, while the apparent Michaelis-Menten constant Km was 1.425 mM. These findings indicated excellent electrocatalytic activity of the modified electrode towards oxidation of EP. The developed biosensor successfully detected EP in spiked mouse serum as well as epinephrine hydrochloride injection with high selectivity, sensitivity, stability, and accuracy.

Albumin Nanoparticles Increase the Efficacy of Doxorubicin Hydrochloride Liposome Injection Based on Threshold Theory.

One of the most significant reasons hindering the clinical translation of nanomedicines is the rapid clearance of intravenously injected nanoparticles by the mononuclear phagocyte system, particularly by Kupffer cells in the liver, leading to an inefficient delivery of nanomedicines for tumor treatment. The threshold theory suggests that the liver's capacity to clear nanoparticles is limited, and a single high dose of nanoparticles can reduce the hepatic clearance efficiency, allowing more nanomedicines to reach tumor tissues and enhance therapeutic efficacy. Building upon this theory, researchers have conducted numerous validation studies based on the same nanoparticle carrier systems. These studies involve the use of albumin nanoparticles to improve the therapeutic efficacy of albumin nanomedicines as well as polyethylene glycol (PEG)-modified liposomal nanoparticles to enhance the efficacy of PEGylated liposomal nanomedicines. However, there is no research indicating the feasibility of the threshold theory when blank nanoparticles and nanomedicine belong to different nanoparticle carrier systems currently. In this study, we prepared two different sizes of albumin nanoparticles by using bovine serum albumin. We used the marketed nanomedicine liposomal doxorubicin hydrochloride injection (trade name: LIBOD, manufacturer: Shanghai Fudan-zhangjiang Biopharmaceutical Co., Ltd.), as the representative nanomedicine. Through in vivo experiments, we found that using threshold doses of albumin nanoparticles still can reduce the clearance rate of LIBOD, prolong its time in vivo, increase the area under the plasma concentration-time curve (AUC), and also lead to an increased accumulation of the drug at the tumor site. Furthermore, evaluation of in vivo efficacy and safety further indicates that threshold doses of 100 nm albumin nanoparticles can enhance the antitumor effect of LIBOD without causing harm to the animals. During the study, we found that the particle size of albumin nanoparticles influenced the in vivo distribution of the nanomedicine at the same threshold dose. Compared with 200 nm albumin nanoparticles, 100 nm albumin nanoparticles more effectively reduce the clearance efficiency of LIBOD and enhance nanomedicine accumulation at the tumor site, warranting further investigation. This study utilized albumin nanoparticles to reduce hepatic clearance efficiency and enhance the delivery efficiency of nonalbumin nanocarrier liposomal nanomedicine, providing a new avenue to improve the efficacy and clinical translation of nanomedicines with different carrier systems.

Initiation of Apomorphine Hydrochloride Injection (Apokyn) in the Absence of an Antiemetic in People with Parkinson’s Disease (P4-3.009)

Initiation of Apomorphine Hydrochloride Injection (Apokyn) in the Absence of an Antiemetic in People with Parkinson’s Disease (P4-3.009)

Effect of dual fluorescence imaging in identifying central lymph nodes and parathyroid glands during thyroid cancer surgery

Objective: To investigate the effect of dual fluorescence imaging in identifying central lymph nodes and parathyroid glands during thyroid cancer surgery. Methods: This study was a cross-sectional study. Patients who underwent surgery for papillary thyroid cancer (PTC) at the Department of Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University between January 2022 and September 2023 were included. All patients underwent thyroid lobectomy or total resection, and central lymph node dissection was performed at the same time. During the operation, tracing injection of mitoxantrone hydrochloride and 785 nm and 660 nm dual fluorescence imaging technique were used to measure the fluorescence intensity (FI) of parathyroid glands, central lymph nodes and background. After correcting to obtain the standardized FI, the paired t-test was used to compare the standardized FI of the parathyroid glands and central lymph nodes, and the Spearman's rank correlation analysis was used to analyze the relationship between the standardized FI and various clinical indicators. Results: The study included 30 patients (8 males and 22 females), with a mean age of (41.8±10.4) years. A total of 76 parathyroid glands and 234 central lymph nodes were identified under dual fluorescence imaging, and the standardized FI of parathyroid glands was less than that of central lymph nodes (44.7±16.8 vs 99.5±28.4, P<0.001). The visualization rate, false rate and miscut rate of parathyroid glands under 785 nm wavelength excitation light were 98.7% (76/77), 0 (0/77) and 1.3% (1/77), respectively (one case with no visualization and miscutting parathyroid gland was the encapsulated type). The visualization rate of central lymph nodes under 660 nm wavelength excitation light was 98.7% (234/237). There was no significant correlation between FI and clinical indicators such as gender, age, height, weight, body mass index, preoperative thyroid stimulating hormone, thyroglobulin antibody, thyroid microsomal antibody, serum calcium, parathyroid hormone level and surgical procedure (all P>0.05). Conclusion: Dual fluorescence imaging of central lymph nodes and parathyroid glands can improve the ability to identify parathyroid gland while assisting central lymph node dissection.

Effect of moxibustion combined with intraperitoneal injection of benazepril on endoplasmic reticulum stress-related protein phosphorylation in rats with chronic heart failure.

To observe the effect of moxibustion at "Xinshu"(BL15) and "Feishu"(BL13) combined with intraperitoneal injection of benazepril on cardiac function and phosphorylation of protein kinase R-like endoplasmic reticulum kinase (PERK) and eukaryotic initiation factor 2α (elF2α) proteins in myocardium of rats with chronic heart failure (CHF), so as to explore its potential mechanism underlying improvement of CHF. A total of 42 male SD rats were randomly assigned to blank control (n=10), CHF model (n=7), medication (benazepril, n=8), moxibustion (n=8) and moxibustion+benazepril (n=9) groups, after cardiac ultrasound model identification and elimination of the dead. The CHF model was established by intraperitoneal injection of doxorubicin hydrochloride (DOX), once every week for 6 weeks. Mild moxibustion was applied to bilateral BL15 and BL13 regions for 20 min, once daily for 3 weeks. The rats of the medication group and moxibustion+benazepril group (benazepril was given first, followed by moxibustion) received intraperitoneal injection of benazepril (0.86 mg/kg) solution once daily for 3 weeks . The cardiac ejection fraction (EF) and left ventricular fractional shortening (FS) were measured using echocardiography. Histopathological changes of the cardiac muscle tissue were observed under light microscope after hematoxylin-eosin (H.E.) staining. Serum contents of B-type brain natriuretic peptide (BNP) and angiotensin Ⅱ (AngⅡ) were measured by enzyme-linked immunosorbent assay (ELISA). The expressions of phospho-PERK (p-PERK) and phospho-elF2α (p-elF2α) in the myocardium were detected by Western blot. Compared with the blank control group, the EF and FS of the left cardiac ventricle were significantly decreased (P<0.01), while the contents of serum BNP and AngⅡ, and expression levels of p-PERK and p-eIF2α significantly increased in the model group (P<0.01). In comparison with the model group, both the decreased EF and FS and the increased BNP and AngⅡ contents as well as p-PERK and p-elF2α expression levels were reversed by moxibustion, medication and moxibustion+benazepril (P<0.01). The effects of moxibustion+benazepril were markedly superior to those of simple moxibustion and simple medication in raising the levels of EF and FS rate and in down-regulating the contents of BNP, Ang Ⅱ, levels of p-PERK and p-elF2α (P<0.01, P<0.05). Outcomes of H.E. staining showed irregular arrangement of cardiomyocytes, cell swelling, vacuole and inflammatory infiltration in the model group, which was relatively milder in the 3 treatment groups. The effects of moxibustion+benazepril were superior to those of moxibustion or benazepril. Moxibustion combined with Benazepril can improve the cardiac function in CHF rats, which may be related to its functions in down-regulating the expression levels of myocardial p-PERK and p-elF2α to inhibit endoplasmic reticulum stress response.

Clostridium butyricum inhibits the inflammation in children with primary nephrotic syndrome by regulating Th17/Tregs balance via gut-kidney axis

BackgroundPrimary nephrotic syndrome (PNS) is a common glomerular disease in children. Clostridium butyricum (C. butyricum), a probiotic producing butyric acid, exerts effective in regulating inflammation. This study was designed to elucidate the effect of C. butyricum on PNS inflammation through the gut-kidney axis.MethodBALB/c mice were randomly divided into 4 groups: normal control group (CON), C. butyricum control group (CON+C. butyricum), PNS model group (PNS), and PNS with C. butyricum group (PNS+C. butyricum). The PNS model was established by a single injection of doxorubicin hydrochloride (DOX) through the tail vein. After 1 week of modeling, the mice were treated with C. butyricum for 6 weeks. At the end of the experiment, the mice were euthanized and associated indications were investigated.ResultsSince the successful modeling of the PNS, the 24 h urine protein, blood urea nitrogen (BUN), serum creatinine (SCr), urine urea nitrogen (UUN), urine creatinine (UCr), lipopolysaccharides (LPS), pro-inflammatory interleukin (IL)-6, IL-17A were increased, the kidney pathological damage was aggravated, while a reduction of body weights of the mice and the anti-inflammatory IL-10 significantly reduced. However, these abnormalities could be dramatically reversed by C. butyricum treatment. The crucial Th17/Tregs axis in PNS inflammation also was proved to be effectively regulated by C. butyricum treatment. This probiotic intervention notably affected the expression levels of signal transducer and activator of transcription 3 (STAT3), Heme oxygenase-1 (HO-1) protein, and retinoic acid-related orphan receptor gamma t (RORγt). 16S rRNA sequencing showed that C. butyricum could regulate the composition of the intestinal microbial community and found Proteobacteria was more abundant in urine microorganisms in mice with PNS. Short-chain fatty acids (SCFAs) were measured and showed that C. butyricum treatment increased the contents of acetic acid, propionic acid, butyric acid in feces, acetic acid, and valeric acid in urine. Correlation analysis showed that there was a closely complicated correlation among inflammatory indicators, metabolic indicators, microbiota, and associated metabolic SCFAs in the gut-kidney axis.ConclusionC. butyricum regulates Th17/Tregs balance via the gut-kidney axis to suppress the immune inflammatory response in mice with PNS, which may potentially contribute to a safe and inexpensive therapeutic agent for PNS.