The paper uses computer multimedia technology to collect and switch audio and video signals, constructs the remote High Definition ( HD) surgery demonstration system which supports live broadcast, recorded broadcast, rebroadcast and video-on-demand depending on the network communication routing technology.It introduces functions, design scheme and composition of the system and points out that the system can realize HD video transmission and video talkback between the surgery scene and the classroom.Thus, tech-nical level of clinical surgery teaching can be enhanced.

Intraperitoneal administration of timosaponin A-III (TA-III) has therapeutic effects on high-fat diet-induced metabolic dysfunction-associated steatotic liver disease (MASLD), but oral administration has no effect. This suggests that gut microbiota may affect the oral bioavailability of TA-III. Metabolic dysfunction-associated steatohepatitis (MASH) is an inflammatory subtype of MASLD. To investigate the therapeutic effect of different administration modes of TA-III on MASH and its relationship with gut microbiota metabolism. In this study, a MASH mouse model was induced by choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD). Comparing the therapeutic effect of intraperitoneal injection (10 mg·kg^-1, ip) and intragastric administration (100 mg·kg^-1, ig) of TA-III. The concentration of TA-III in serum of rats under the two administration modes was analyzed. On this basis, the metabolic effect of gut microbiota on TA-III in mice was verified by the experiment of metabolism of gut microbiota in vitro. The pharmacokinetic experiment of combined antibiotic intervention in mice further verified the metabolism of TA-III by gut microbiota in mice. Finally, the concentration of TA-III in serum of mice after the administration of TA-III by intragastric administration under different antibiotic intervention conditions was compared, and 16S rRNA sequencing analysis was combined to find the key bacteria that may participate in the metabolism of TA-III. The animal welfare and experimental procedures in this paper were in accordance with the provisions of the Animal Ethics Committee of Shanghai University of Traditional Chinese Medicine. The ethics approval number is PZSHUTCM2307030004 and PZSHUTCM2310200003. The results showed that TA-III (10 mg·kg^-1, ip) had definite therapeutic effect on MASH mice, but TA-III (100 mg·kg^-1, ig) was ineffective. The analysis showed that the prototype concentration of TA-III in serum and liver of mice in TA-III (100 mg·kg^-1, ig) was significantly lower than TA-III (10 mg·kg^-1, ip), suggesting that the oral administration of TA-III may be metabolized by gut microbiota. The concentration of TA-III in serum of streptomycin (Str) treated mice was higher than normal mice. Combined with 16S rRNA gene sequencing analysis, it was found that the abundance of Akkermansia_muciniphila (A. muciniphila) was significantly reduced in the Str group. In vitro experiments showed that A. muciniphila could metabolize TA-III. In conclusion, gut microbiota is an important factor affecting the efficacy of TA-III administration through the gastrointestinal tract, in which A. muciniphila may play an important role.

Administration, Oral ; Adult ; Atrial Flutter ; drug therapy ; physiopathology ; Digoxin ; therapeutic use ; Echocardiography ; Female ; Fetal Diseases ; drug therapy ; physiopathology ; Humans ; Hydrops Fetalis ; drug therapy ; physiopathology ; Infant, Newborn ; Male ; Pregnancy

Objective To study the effect of platelet-derived growth factor(PDGF)and lysosomes on lung injury in macaque with early-phase endotoxie shock.Method Eleven macaques were randomly divided into two groups,namely,control group(Co group,n=5)iand endotoxic group(En group,n=6).The macaque of the Co group injected with 1 ml/kg normal saline and the macque of the En group received a dose of 2.8 mg/kg Lipopolysaccharides(LPS)i.v.The blood gas was detected at 120 minutes after LPS challenging. Uhrastructure,cytochemistry of acid phosphatase(ACPase)detection by electronic microscopy and immunohistochemical assay of PDGF were completed in hmgs of all the macaque .Results Administration of LPS did not change the parameters of gas exchange,namely,PaO_2,PaO_2/Fi and PaCO_2.In the early phase,of endotoxic shock,ACPase activity products increased and lysosome destroyed in the alveolar cells.The pathologic changes of alveolus,such as degeneration of vessel endothelium,injury of alveolar epithelium and damage of basement membrane,and transudation of blood component were observed by electron microscopy in the En group. However,no pathological changes were found in the control group.By immunohistochemical staining,PDGF on alveolar wall in the En animals was observed,whereas no PDGF protein in the Co macaques was noticed. Conclusions Administration of LPS induced the expression of PDGF in the alveolar wall and lysosome injury in the alveolar cells,as a result of alveolar damage in early-phase endotoxin shock.In the meantime,the parameters of gas exchanges did not change.The PDGF may play an important role in the pathogenesis of lung during the early-phase of endotoxin shock.

In recent years, artificial intelligence (AI) technology has advanced rapidly and has been widely applied in various fields such as medicine and pharmacy, accelerating the drug development process. Focusing on the application of AI in the discovery and optimization of lead compounds, this review provides a detailed introduction to AI-assisted virtual screening and molecular generation methods for discovering lead compounds, while particularly highlighting the cases of AI-drived drugs into clinical trials. Additionally, we briefly outline the application of AI basic algorithm models in quantitative structure-activity relationship (QSAR) and drug repurposing, offering insights for AI-based drug discovery.

Aged ; Female ; Humans ; Hypertriglyceridemia ; blood ; epidemiology ; Male ; Middle Aged ; Prevalence ; Uric Acid ; blood

OBJECTIVETo establish the visual patch clamp whole-cell recording technique and study the properties and functional significance of muscarinic receptor-mediated currents in rat medial vestibular nucleus neurons (MVNn).

METHODSBrain slices containing the MVN were prepared from fifteen Wistar rats. By combining infrared differential interference contrast (IR-DIC) technique and CCD-Camera system with visual patch clamp whole-cell recording technique, twenty healthy neurons were located and muscarinic receptor-mediated currents in rat MVNn were observed and analyzed.

RESULTSVisual patch clamp technique can be used to make direct localization and to make sure of active neuron. In MVNn, a comparison of the current-voltage relationships before and during the application of muscarine, which revealed an increase in the slope of the I-V curve and the reversal potential for this response lay at (-88.4 +/- 4.9) mV (x +/- s), indicates that the activation of muscarinic cholinergic receptors leads to a decrease in potassium current. The test in the voltage sensitivity of the muscarine-induced response, which showed that the effect had a linear current-voltage relationship and reversed at (-86.7 +/- 3.5) mV, indicates that the potassium current blocked by muscarine corresponds to the voltage-insensitive leak potassium current.

CONCLUSIONSVisual patch clamp technique, which was considered better than blind patch clamp technique, can improve the success of sealing process. By the analysis of muscarinic receptor-mediated currents, the data provide support that muscarinic cholinergic mechanisms play a prominent role in the modulation of the excitability of MVNn and also offer a new idea for the efficacy of anticholinergic drugs.

Animals ; Electrophysiological Phenomena ; Neurons ; physiology ; Patch-Clamp Techniques ; Rats ; Rats, Wistar ; Receptors, Muscarinic ; physiology ; Vestibular Nuclei ; physiology

OBJECTIVETo study the membrane properties of rat medial vestibular nucleus (MVN) neurons and their firing responses to simulated input signals of peripheral vestibular system, and to discuss how the intrinsic membrane properties contribute to physiologic functions in central vestibular system.

METHODSBy using infrared differential interference contrast technique, whole-cell recordings were made from rat MVN neurons under direct observation. On the basis of their averaged action potential shapes, the MVN neurons were classified. Linear and non-linear currents were put into the neurons to simulate the input signals of peripheral vestibular system. The differences of intrinsic membrane properties and firing response dynamics were observed between two types.

RESULTSThe discharge activities were recorded in MVN neurons, which remained in low Ca2+-high Mg2+ artificial cerebrospinal fluid (ACSF). Neurons are classified as type A (33%) characterized by a single deep after-hyperpolarization (AHP) and A-like rectification, or type B (63%) characterized by double AHP, and another two neurons with all or none of the characters. The passive membrane properties were not significantly different between type A and type B neurons, while part of active membrane properties was significantly different. Both type A and B neurons well responded to simulated current inputs, but disparities existed in response range and firing dynamics.

CONCLUSIONSThe discharge activities of MVN neurons were initiated by their intrinsic membrane properties. Most MVN neurons were classified as type A and B, while several showed unrepresentative firing properties. Linear and nonlinear inputs evoked a heterogeneous range of firing responses. The differences of response range and firing dynamics between neurons may determine their different physiological functions.

Action Potentials ; Animals ; Neurons ; metabolism ; physiology ; Patch-Clamp Techniques ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Vestibular Nuclei ; cytology ; metabolism ; physiology

Objective To assess the efficacy, safety, and tolerability of verapamil as prophylactic therapy for patients withcluster headache, and compare its efficacy with that of prednisone.Methods Prospectively, according to the order of visit, a total of 45 patients with episodic cluster headache or chronic cluster headache were divided into verapamil treatment group (n=23, the odd) and prednisone treatment group (n=22, the even). The seizure frequency, and times of and dosage of using acesodyne were observed in the 2 groups 1 week before treatment, 1 and 2 week after treatment.Results Mean frequency of headache occurrence decreased from 8.78 to 2.52 and 1.35 times,respectively, in the first and second week of treatment in the verapamil group (P=0.000) and from 8.09 to 2.95 and 1.64 times, respectively, at the corresponding time in the prednisone group (P=0.000). Mean abortive agent consumption decreased from 8.09 to 1.65 and 0.48 pills, respectively, in the verapamil group (P=0.000) and from 7.77 to 2.59 and 1.36 pills, respectively, in the prednisone group (P=0.000) in the first and second week of treatment; no significant differences existed in the mean frequency of headache and abortive agent consumption between the 2 groups at the same time point (P＞0.05). The side effects of verapamil were mild, including dizziness, constipation and bradycardia and those ofprednisone were insomnia, increased appetite combined with weight gain and discomfort of abdomen. Conclusion Both verapamil and prednisone prophylaxis therapy for episodic and chronic cluster headache yield significant reduction in headache frequency and abortive agent consumption; choices can be made according to different situations.

Objective To investigate the effect of ursolic acid(UA) on NOX2/ROS/NLRP3 inflammasome activation in carbon tetrachloride(CCl4)-induced liver fibrosis SD rat,and to observe the improvement of collagen deposition in liver tissues. Methods All rats were randomly divided into 3 group:control group,CCl4model group,UA treatment group. Liver fibrosis model SD rats was established by the CCl4-induced method and half of them was used as UA treatment group. Serum ALT was detected by ALT detection kit.The liver pathology and collagen deposition were ob-served by HE and Sirius-red staining. The mRNA expression of Nox2,Nlrp3,Caspase1,IL-1β in liver tissues was detected by RT-qPCR. The protein expression of NOX2,NLRP3,caspase-1 and IL-1β in liver tissues was detected by Western blot and immunohistochemistry and the ROS generation in liver tissues was detected by DCFH-DA fluores-cence probe. Results Compared with control group,in the CCl4model group,the serum ALT was much higher (P<0.05);the Ishak's fibrosis score and collagen deposition was significantly increased(P<0.05) and mRNA of Nox2, Nlrp3,Caspase1,IL-1β was increased.In addition,both the NOX2,NLRP3,caspase-1 p10 and IL-1β protein expres-sion and ROS level (P<0.05) of CCl4model group were significant increased.Compared with CCl4model group,in the UA treatment group Ishak's fibrosis score,collagen deposition and ALT decreased.Both mRNA expression of the Nox2, Nlrp3,Caspase1,IL-1β and protein expression of NOX2,NLRP3,caspase-1 p10 and IL-1β as well as ROS were signif-icant decreased,but the caspase-1 p45 protein level has no difference among all these groups (P>0.05). Conclusions Ursolic acid attenuates the liver injury and reduces the collagen deposition,which may relate to its inhibitory effects on NOX2/ROS/NLRP3 inflammasome activation to reduce IL-1β releasing.