This study identified blood-entering components of Anshen Dropping Pills and explored their anti-insomnia effects and mechanisms. The main blood-entering components of Anshen Dropping Pills were detected and identified by UPLC-Q-TOF-MS/MS. The rationality of the formula was assessed by using enrichment analysis based on the relationship between drugs and symptoms, and core targets of its active components were selected as the the potential anti-insomnia targets of Anshen Dropping Pills through network pharmacology analysis. Furthermore, protein-protein interaction(PPI) network, Gene Ontology(GO) enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis were performed on the core targets. An active component-core target network for Anshen Dropping Pills was constructed. Finally, the effects of low-, medium-, and high-dose groups of Anshen Dropping Pills on sleep episodes, sleep duration, and sleep latency in mice were measured by supraliminal and subliminal pentobarbital sodium experiments. Moreover, total scores of the Pittsburgh sleep quality index(PSQI) scale was used to evaluate the changes before and after the treatment with Anshen Dropping Pills in a clinical study. The enrichment analysis based on the relationship between drugs and symptoms verified the rationality of the Anshen Dropping Pills formula, and nine blood-entering components of Anshen Dropping Pills were identified by UPLC-Q-TOF-MS/MS. The network proximity revealed a significant correlation between eight components and insomnia, including magnoflorine, liquiritin, spinosin, quercitrin, jujuboside A, ginsenoside Rb_3, glycyrrhizic acid, and glycyrrhetinic acid. Network pharmacology analysis indicated that the major anti-insomnia pathways of Anshen Dropping Pills involved substance and energy metabolism, neuroprotection, immune system regulation, and endocrine regulation. Seven core genes related to insomnia were identified: APOE, ALB, BDNF, PPARG, INS, TP53, and TNF. In summary, Anshen Dropping Pills could increase sleep episodes, prolong sleep duration, and reduce sleep latency in mice. Clinical study results demonstrated that Anshen Dropping Pills could decrease total scores of PSQI scale. This study reveals the pharmacodynamic basis and potential multi-component, multi-target, and multi-pathway effects of Anshen Dropping Pills, suggesting that its anti-insomnia mechanisms may be associated with the regulation of insomnia-related signaling pathways. These findings offer a theoretical foundation for the clinical application of Anshen Dropping Pills.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Tandem Mass Spectrometry/methods* ; Sleep Initiation and Maintenance Disorders/metabolism* ; Mice ; Network Pharmacology ; Male ; Chromatography, High Pressure Liquid ; Humans ; Protein Interaction Maps/drug effects* ; Sleep/drug effects* ; Female ; Adult

Objective:To evaluate the feasibility, safety, treatment outcome, and the individualized surgical procedure selection of the interventional treatments of chylous leakage.Methods:From July 2019 to January 2022, the clinical data of 60 consecutive patients with chylous leakage underwent interventional treatment were respectively analyzed. The cases included chylothorax ( n=37), chylous ascites ( n=10), chyluria ( n=4), chylothorax combined with chylous ascites ( n=5), chylothorax combined with chylopericardium ( n=2), and pelvic chylous effusion ( n=2). Conservative treatment was considered to have failed for all patients. The lymphangiography was firstly performed to detect chylous leakage, then an individualized procedure was selected according to the lymphangiography results. The treatment outcomes and complications were recorded, and follow-up was performed. Results:Lymphangiography was technically successful in 55 of 60 patients (91.7%), and no cisterna chyli and thoracic duct opacification was observed in 5 patients. The procedures for the patients included lymphangiography alone ( n=23), thoracic duct embolization ( n=23), thoracic duct disruption ( n=5), lymphatic embolization for pelvic chylous effusion ( n=4), and balloon plasty for thoracic duct ( n=5). Clinical success was achieved in 53 of 60 cases (88.3%). The complication rate was 8.3% (5/60), and all complications were minor. The median follow-up time was 11 months (range 0.5-30 months) for 56 patients, and 4 patients were lost to follow-up. There was one patient presenting the reoccurrence of symptom, and 8 patients died. Conclusions:The interventional treatment of chylous leakage is safe with good outcomes and low complication rate. Individualized treatment procedures based on the lymphangiography findings is feasible and with good curative effect.

Pesticides' overuse and misuse have been reported to induce ingredient variations in herbal medicine, which is now gaining attention in the medicinal field as a form of alternative medicine. To date, available studies on pesticide-induced ingredient variations of herbal medicine are limited only on a few compounds and remain most others unexamined. In this study, a plant metabolomics-based strategy was performed to systematically explore the effects of two frequently used insecticides on the comprehensive constituents of Lonicerae Japonicae Flos (LJF), the flower buds of Lonicera japonica Thunb. Field trials were designed on a cultivating plot of L. japonica with controls and treatments of imidacloprid (IMI) and compound flonicamid and acetamiprid (CFA). Unbiased metabolite profiling was conducted by ultra-high performance liquid chromatography/quadrupole-Orbitrap mass spectrometer. After data pretreatment by automatic extraction and screening, a data matrix of metabolite features was submitted for statistical analyses. Consequently, 29 metabolic markers, including chlorogenic acids, iridoids and organic acid-glucosides were obtained and characterized. The relative quantitative assay was subsequently performed to monitor their variations across flowering developments. This is the first study that systematically explored the insecticide-induced metabolite variations of LJF while taking into account the inherent variability of flowering development. The results were beneficial for holistic quality assessment of LJF and significant for guiding scientific use of pesticides in the large-scale cultivation.

The main treatment strategies for chronic pancreatitis in young patients include therapeutic endoscopic retrograde cholangio-pancreatography (ERCP) intervention and surgical intervention. Therapeutic ERCP intervention is performed much more extensively for its minimally invasive nature, but a part of patients are referred to surgery at last. Historical and follow-up data of 21 young patients with chronic pancreatitis undergoing duodenum-preserving total pancreatic head resection were analyzed to evaluate the outcomes of therapeutic ERCP intervention and surgical intervention in this study. The surgical complications of repeated therapeutic ERCP intervention and surgical intervention were 38% and 19% respectively. During the first therapeutic ERCP intervention to surgical intervention, 2 patients developed diabetes, 5 patients developed steatorrhea, and 5 patients developed pancreatic type B pain. During the follow-up of surgical intervention, 1 new case of diabetes occurred, 1 case of steatorrhea recovered, and 4 cases of pancreatic type B pain were completely relieved. In a part of young patients with chronic pancreatitis, surgical intervention was more effective than therapeutic ERCP intervention on delaying the progression of the disease and relieving the symptoms.
Adolescent ; Adult ; Cholangiopancreatography, Endoscopic Retrograde ; adverse effects ; methods ; Diabetes Mellitus ; etiology ; Female ; Follow-Up Studies ; Humans ; Male ; Pain, Postoperative ; etiology ; Pancreatectomy ; adverse effects ; methods ; Pancreatitis, Chronic ; surgery ; Postoperative Complications ; etiology ; Steatorrhea ; etiology ; Treatment Outcome ; Young Adult

The main treatment strategies for chronic pancreatitis in young patients include therapeutic endoscopic retrograde cholangio-pancreatography (ERCP) intervention and surgical intervention. Therapeutic ERCP intervention is performed much more extensively for its minimally invasive nature, but a part of patients are referred to surgery at last. Historical and follow-up data of 21 young patients with chronic pancreatitis undergoing duodenum-preserving total pancreatic head resection were analyzed to evaluate the outcomes of therapeutic ERCP intervention and surgical intervention in this study. The surgical complications of repeated therapeutic ERCP intervention and surgical intervention were 38% and 19% respectively. During the first therapeutic ERCP intervention to surgical intervention, 2 patients developed diabetes, 5 patients developed steatorrhea, and 5 patients developed pancreatic type B pain. During the follow-up of surgical intervention, 1 new case of diabetes occurred, 1 case of steatorrhea recovered, and 4 cases of pancreatic type B pain were completely relieved. In a part of young patients with chronic pancreatitis, surgical intervention was more effective than therapeutic ERCP intervention on delaying the progression of the disease and relieving the symptoms.

OBJECTIVETo investigate the effect of propofol at doses for different anesthesia depths on γ-aminobutyric acid (GABA) in different cerebral regions at propofol uptake equilibrium in dogs.

METHODSTwelve 12-18-month-old healthy hybrid dogs weighing 10-12 kg were randomly divided into light anesthesia group (n=6) and deep anesthesia group (n=6) with a single bolus dose of propofol (5.5 and 7.0 mg/kg, respectively) completed in 15 s followed by intravenous propofol infusion at a constant rate (55 and 70 mg·kg(-1)·h(-1), respectively). Blood samples (2 ml) were taken from the internal carotid artery and jugular vein to measure plasma propofol concentrations 50 min after the start of the infusion. The dogs were then sacrificed and tissues were taken from different brain regions and the cervical cord to measure GABA concentrations using high-pressure liquid chromatography (HPLC).

RESULTSThe plasma propofol concentrations in internal carotid artery and jugular vein were similar in both light anesthesia group (3.00 ± 0.31 and 3.10 ± 0.51 µg/ml, respectively, P>0.05) and deep anesthesia group (6.41 ± 0.05 and 6.40 ± 0.11 µg/ml, respectively, P>0.05). GABA concentrations in the brain regions were significantly higher in deep anesthesia group than in light anesthesia group (P<0.05). The dorsal thalamus and hypothalamus showed greater GABA variations [(83.83 ± 2.230%) and (85.83 ± 1.72)%] compared to other brain regions at different anesthesia depths (P<0.05).

CONCLUSIONSIn both groups, plasma propofol concentrations in the internal carotid artery and internal jugular vein reach equilibrium at 50 min of propofol infusion. The variation of GABA is associated with the anesthesia depth of propofol, and GABA variation in the dorsal thalamus and hypothalamus plays an important role in propofol anesthesia.

Anesthetics, Intravenous ; pharmacokinetics ; Animals ; Brain ; metabolism ; Dogs ; Female ; Male ; Propofol ; blood ; pharmacokinetics ; gamma-Aminobutyric Acid ; metabolism

OBJECTIVETo observe the regional distribution of propofol in canine spinal cord under noxious stimulation.

METHODSTwelve healthy hybrid dogs (12-18 months old, weighing 10-12 kg) were randomly divided into control group (n=6) and stimulation group (n=6). All the dogs were anesthetized with a single bolus dose of propofol (7 mg/kg) in 15 seconds followed by propofol infusion at a constant rate of 70 mg/kg/h via the great saphenous vein of the right posterior limb. In the stimulation group, the tails of the dogs were clamped for 5 min after 45 min of propofol infusion. Blood samples were taken from the internal carotid artery and internal jugular vein at 50 min after propofol infusion to detect plasma propofol concentrations by high-pressure liquid chromatography (HPLC). The dogs were then immediately sacrificed by decapitation and the frontal horn, posterior horn, intermediate zone, frontal funiculus, posterior funiculus and lateral funiculus of the spinal cord were dissected for determination of propol content by HPLC.

RESULTSThe plasma concentrations of propofol in the internal carotid artery and internal jugular vein were 5.07-/+0.23 and 5.03-/+0.10 microg/ml in the stimulation group, respectively showing no significant differences from those in the control group (5.09-/+0.03 and 5.08-/+0.03 microg/ml, P>0.05). In the control group, the propofol concentration was 5.09-/+0.08 microg/g in the frontal horm, 5.10-/+0.08 microg/g in the posterior horn, 5.05-/+0.19 microg/g in the intermediate zone, 5.06-/+0.14 microg/g in the frontal funiculus, 5.06-/+0.15 microg/g in the posterior funiculus and 5.06-/+0.41 microg/g in the lateral funiculus, showing no significant differences (P>0.05). The propofol concentrations in the frontal horn (7.65-/+0.47 microg/g) and posterior funiculus (7.06-/+0.82 microg/g) in the stimulation group were significantly higher than those in the other spinal cord tissues (P<0.05) and those in the control group (P<0.05).

CONCLUSIONAt 50 min after intravenous injection of propofol at a constant rate of 70 mg/kg/h, plasma propofol concentrations in the internal carotid artery and internal jugular vein reaches equilibrium with a balanced distribution in all the spinal cord regions. Propofol concentration can be higher in the frontal horn and posterior funiculus under noxious stimulation.

Animals ; Dogs ; Female ; Male ; Nociceptors ; drug effects ; physiology ; Pain ; physiopathology ; Physical Stimulation ; Propofol ; administration & dosage ; pharmacokinetics ; pharmacology ; Random Allocation ; Spinal Cord ; metabolism

OBJECTIVETo investigate the cerebral uptake and regional distribution of propofol when plasma propofol concentration reaches equilibrium in the internal carotid artery and internal jugular vein in dogs.

METHODSEight male hybrid dogs aged 12-18 months weighing 10-12 kg were anesthetized with propofol at a single bolus (7 mg/kg) in 15 s followed by propofol infusion at a constant rate of 70 mg.kg(-1).h(-1) via the great saphenous vein of the right posterior limb. Blood samples were taken from the internal carotid artery and internal jugular vein at 30 min (T30) after propofol infusion for measurement of plasma propofol concentrations by high-pressure liquid chromatography (HPLC). The thalamus, epithalamus, metathalamus, hypothalamus, subthalamus, frontal lobe, parietal lobe, temporal lobe, hippocampus, cingulate gyrus, cerebellum, midbrain, pons, medulla oblongata and cervical cord were then dissected to determine propofol concentrations in these tissues by HPLC.

RESULTSThe propofol concentrations in the internal carotid artery and internal jugular vein blood plasma were comparable at T30 (6.16-/+1.02 vs 6.17-/+1.00 microg/ml, P>0.05). The propofol concentration was 6.11-/+1.07 microg/g in the epithalamus, 6.14-/+0.98 microg/g in the metathalamus, 6.12-/+1.02 microg/g in the hypothalamus, 6.15-/+1.00 microg/g in the subthalamus, 6.20-/+1.03 microg/g in the frontal lobe, 6.18-/+1.02 microg/g in the parietal lobe, 6.13-/+1.00 microg/g in the temporal lobe, 6.07-/+0.99 microg/g in the hippocampus, 6.14-/+1.06 microg/g in the cingulate gyrus, 6.15-/+1.00 microg/g in the cerebellum, 6.13-/+1.05 microg/g in the midbrain, 6.18-/+1.01 microg/g in the pons, 6.15-/+0.93 microg/g in the medulla oblongata, and 6.13-/+1.00 microg/g in the cervical cord, showing no significant differences in the distributions (P>0.05). Propofol concentration in the thalamus (8.68-/+0.88 microg/g) was significantly higher than those in the other brain tissues (P<0.05).

CONCLUSIONSAt the constant intravenous propofol injection rate of 70 mg.kg(-1).h(-1), plasma propofol concentration reaches equilibrium 30 min after the injection in the internal carotid artery and internal jugular vein with even distribution in the cerebral tissues in dogs, but the thalamus contains high propofol concentration.

Absorption ; Anesthetics, Intravenous ; blood ; pharmacokinetics ; Animals ; Brain ; metabolism ; Carotid Artery, Internal ; metabolism ; Dogs ; Jugular Veins ; metabolism ; Male ; Propofol ; blood ; pharmacokinetics ; Thalamus ; metabolism

OBJECTIVETo observe the therapeutic effect of Shenyin Oral Liquid (SOL) in relieving mild cognitive impairment (MCI) and decreasing the Alzheimer's disease (AD) transformation rate.

METHODSOne hundred and seventeen MCI patients were randomly assigned to the Chinese medicine group (42 cases), the vitamin E group (38 cases) and the placebo group (37 cases). The treatment course was 12 months and a 6-month follow-up was conducted after ending the treatment course.

RESULTSAfter treatment, the scores of clock drawing test (CDT), nonsensical figure recognition and mini-mental state examination (MMSE) raised significantly in the Chinese medicine group (P < 0.05 or P < 0.01), the activity of acetylcholine esterase in erythrocytic membrane was lower in the Chinese medicine group than that in the placebo group and the Vitamin E group (P < 0.05 or P < 0.01). Six months after the treatment, there were 2 and 5 cases in the placebo group and the vitamin E group which were diagnosed as AD, respectively, and none in the Chinese medicine group.

CONCLUSIONSOL has an effect similar to cholinesterase inhibitor, it could improve cognitive function in MCI patients and reduce the AD transformation rate in them.

Aged ; Alzheimer Disease ; prevention & control ; Cognition Disorders ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Memory ; drug effects ; Mental Status Schedule ; Middle Aged ; Nootropic Agents ; therapeutic use ; Phytotherapy ; Treatment Outcome

OBJECTIVETo evaluate postoperative glottic area and vocal quality of three various surgical techniques for treating bilateral vocal cord paralysis, including laser arytenoidectomy (Group A, 24 cases), reinnervation of the posterior cricoarytenoid muscle by phrenic nerve (Group B, 9 cases) and arytenoidectomy accompanying lateral cordopexy by extralaryngeal approach (Woodman's procedure, Group C, 13 cases).

METHODS46 cases suffered from bilateral recurrent laryngeal nerve injury were included in our study. The pre-postoperative glottic measurement and vocal acoustic parameters were analyzed.

RESULTSThe decannulated cases in group A and group B and group C were 22, 8, 13 respectively. The post-operative mean maximal glottic area was (47.2 +/- 7.4) mm2, (78.3 +/- 16.0) mm2, (48.1 +/- 6.5) mm2 respectively. Group B cases glottic area was larger than that of group A and group C (t value were 4.46 and 3.85, P value were 0.000 and 0.001). No significant difference was found between group A and group C (t = 1.68, P = 0.101). After surgery, in group A, 17 cases voice quality was the same compared with that of before surgery, and 7 cases voice quality had become worse; In group B, the voice quality had become better in 5 cases, completely recovered in 1 case, and had not change in 3 cases; In group C, the voice quality had become deteriorated in 10 cases and no change in 3 cases. And in group B, ipsilateral diaphragm paralysis in 9 cases after surgery, whose vital capacity and forced vital capacity had decreased to 72%-84%, 76%-84% of that before the surgery respectively; and the diaphragm mobility had recovered by 35%-76% respectively, while vital capacity and forced vital capacity had become 93%-97%, 91%-98% of that before the surgery. In Group B, all cases' pulmonary function was normal half a year postoperatively.

CONCLUSIONSReinnervation of the posterior cricoarytenoid muscle by phrenic nerve seems to be best procedure with better post-operative voice and larger glottic area. Although the sufficient airway for decannulation can be acquired in Group A and Group C, but most of patients in Group A had pre-operative vocal level and badly abnormal in Group C.

Adult ; Aged ; Arytenoid Cartilage ; surgery ; Female ; Glottis ; physiopathology ; Humans ; Laser Therapy ; Male ; Middle Aged ; Phrenic Nerve ; surgery ; Treatment Outcome ; Vocal Cord Paralysis ; physiopathology ; surgery ; Voice Quality ; Young Adult