Objective: To investigate the effects of Zuogui Jiangtang Yishen Formula (左归降糖益肾方, ZGJTYSF) in regulating the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)/caspase-1/gasdermin D (GSDMD) signaling axis on pyroptosis in rats with diabetic kidney disease (DKD). Methods: Fifty male specific pathogen-free (SPF) grade Goto-Kakizaki (GK) rats (12 weeks old) were fed a high-fat diet for one month to establish an early DKD model. Model establishment was confirmed when fasting blood glucose (FBG) ≥ 11.1 mmol/L and urinary albumin-to-creatinine ratio (uACR) ≥ 30 mg/g. The successfully modeled early DKD rats were randomly divided by random number table into five groups (n = 10 per group): model group; dapagliflozin group (1.0 mg/kg, by gavage, served as positive control); and low-, medium-, and high-dose of ZGJTYSF groups (4.9, 9.9, and 19.9 g/kg, respectively, by gavage). Age-matched male SPF Wistar rats (n = 10) served as control group. Rats in control and model groups were gavaged with equivalent volumes of distilled water. Treatment lasted 12 weeks. Changes in uACR, FBG, and renal function were observed in all groups. Hematoxylin-eosin (HE), periodic acid-Schiff (PAS), and Masson staining were used to observe renal histopathological changes. Immunohistochemistry was performed to detect the localization and expression of caspase-1, GSDMD, and NLRP3 in rat renal tissues. Terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) was utilized to detect pyroptosis in renal tissues. Quantitative real-time polymerase chain reaction (qPCR) and Western blot were applied to detect mRNA and protein expression levels of NLRP3, caspase-1, GSDMD, interleukin (IL)-1β, and IL-18. Results: Compared with model group, all doses of ZGJTYSF showed reductions in FBG, with medium- and high-dose of ZGJTYSF groups demonstrating significant decreases at week 8 and 12 (P < 0.05). For uACR, all doses of ZGJTYSF groups exhibited a decreasing trend, with high-dose of ZGJTYSF group being significantly lower than low- and medium-dose of ZGJTYSF groups at week 12 (P < 0.05) and showing no significant difference from dapagliflozin group (P > 0.05). No significant differences in renal function parameters (serum creatinine, blood urea nitrogen, and uric acid) were observed among groups (P > 0.05). Histopathological examination revealed milder glomerular and tubular lesions in both ZGJTYSF groups and dapagliflozin group, with renal pathological changes in high-dose of ZGJTYSF group resembling those in dapagliflozin group. Immunohistochemistry demonstrated significantly reduced expression of caspase-1, GSDMD, and NLRP3 in renal tissues of dapagliflozin group and high-dose of ZGJTYSF group compared with model group (P < 0.05 or P < 0.01), while the differences in low- and medium-dose of ZGJTYSF groups were not statistically significant (P > 0.05). TUNEL assay showed significantly fewer TUNEL-positive cells in renal tissues of dapagliflozin and high-dose of ZGJTYSF groups (P < 0.01), indicating a marked reduction in pyroptotic cells. Molecular analysis revealed that compared with model group, both dapagliflozin and high-dose of ZGJTYSF groups showed significantly downregulated mRNA and protein expression levels of NLRP3, caspase-1, GSDMD, IL-1β, and IL-18 in renal tissues (P < 0.01), while low- and medium-dose of ZGJTYSF groups showed downward trends without statistical significance (P > 0.05). Conclusion ZGJTYSF may inhibit renal pyroptosis by regulating the NLRP3/caspase-1/GSDMD signaling axis, thereby preventing and treating early renal injury in DKD and delaying the onset and progression of DKD.

The circadian clock plays a critical role in regulating various physiological processes, including gene expression, metabolic regulation, immune response, and the sleep-wake cycle in living organisms. Post-translational modifications (PTMs) are crucial regulatory mechanisms to maintain the precise oscillation of the circadian clock. By modulating the stability, activity, cell localization and protein-protein interactions of core clock proteins, PTMs enable these proteins to respond dynamically to environmental and intracellular changes, thereby sustaining the periodic oscillations of the circadian clock. Different types of PTMs exert their effects through distincting molecular mechanisms, collectively ensuring the proper function of the circadian system. This review systematically summarized several major types of PTMs, including phosphorylation, acetylation, ubiquitination, SUMOylation and oxidative modification, and overviewed their roles in regulating the core clock proteins and the associated pathways, with the goals of providing a theoretical foundation for the deeper understanding of clock mechanisms and the treatment of diseases associated with circadian disruption.
Protein Processing, Post-Translational/physiology* ; Circadian Rhythm/physiology* ; Humans ; Animals ; CLOCK Proteins/physiology* ; Circadian Clocks/physiology* ; Phosphorylation ; Acetylation ; Ubiquitination ; Sumoylation

Objective To determine the effective dose of dexmedetomidine administered intranasally combined with oral midazolam sedation before pediatric magnetic resonance image(MRI).Methods This is a prospective modified sequential study.Children scheduled for MRI at the Children's Hospital of Zhejiang University School of Medicine from February to March 2023,aged 1 month to 6 years old,with a weight of 6.0-23.5 kg,were enrolled in this study.All children received 0.5 mg/kg oral midazolam,followed by intranasal dexmedetomidine.The initial dose of dexmedetomidine was 0.5 μg/kg,and the intranasal dose of dexmedetomidine was determined using the modified Dixon's up-and-down method with increments or decrements of 0.1 μg/kg.Probit analysis was used for calculating the half effective dose(ED50),95%effective dose(ED95)and the corresponding 95%confidence interval(CI)of intranasal dexmedetomidine combined with oral midazolam for pediatric sedation during MRI.The sedation onset time,wake-up time,vital signs and adverse reactions were recorded.Results Among all the children,the sedation onset time of successful sedation children was(31.21±7.47)min,and the wake-up time was(81.21±26.04)min.The ED50 for effective sedation with intranasal dexmedetomidine combined with oral medication at a dose of 0.5 mg/kg was calculated to be 0.392 μg/kg,with a 95%CI of 0.302-0.461 μg/kg;the ED95 was 0.549 μg/kg,with a 95%CI of 0.473-0.996 μg/kg.There was a statistically significant difference(P<0.05)in heart rate and diastolic blood pressure after sedation compared to the baseline before medication.Two cases of restlessness during the awakening period were observed,but no other adverse reactions occurred.Conclusions The sedation regimen of intranasal dexmedetomidine combined with oral midazolam is non-invasive,easy to implement,safe,and effective.It can be widely used in pediatric MRI.

The current status of exoskeletons was introduced in enhancing individual soldier's battlefield rescue capabilities,promoting the integrated use of battlefield rescue equipment,protecting medical personnel on the battlefield and assisting injured soldiers in rehabilitation training.The challenges of exoskeletons faced in human-machine interaction,power supply endurance,heavy overall structure,restricted movement and high cost were analyzed when applied to medical service support,and some suggestions were proposed accordingly including enhancing technology research and development,integrated application,communication and cooperation and personnel training.References were provided for the application of exoskeletons in China's medical service support.[Chinese Medical Equipment Journal,2024,45(3):71-75]

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the efficacy of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects who were previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extended or switched TMF treatment for 48 weeks. Efficacy was evaluated based on virological, serological, biological parameters, and fibrosis staging. Statistical analysis was performed using the McNemar test, t-test, or Log-Rank test according to the data. Results:593 subjects from the initial TMF group and 287 subjects from the TDF group were included at week 144, with the proportions of HBV DNA<20 IU/ml at week 144 being 86.2% and 83.3%, respectively, and 78.1% and 73.8% in patients with baseline HBV DNA levels ≥8 log10 IU/ml. Resistance to tenofovir was not detected in both groups. For HBeAg loss and seroconversion rates, both groups showed a further increase from week 96 to 144 and the 3-year cumulative rates of HBeAg loss were about 35% in each group. However, HBsAg levels were less affected during 96 to 144 weeks. For patients switched from TDF to TMF, a substantial further increase in the alanine aminotransferase (ALT) normalization rate was observed (11.4%), along with improved FIB-4 scores.Conclusion:After 144 weeks of TMF treatment, CHB patients achieved high rates of virological, serological, and biochemical responses, as well as improved liver fibrosis outcomes. Also, switching to TMF resulted in significant benefits in ALT normalization rates (NCT03903796).

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the safety profile of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects that previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extending or switching TMF treatment for 48 weeks. Safety profiles of kidney, bone, metabolism, body weight, and others were evaluated.Results:666 subjects from the initial TMF group and 336 subjects from TDF group with at least one dose of assigned treatment were included at week 144. The overall safety profile was favorable in each group and generally similar between extended or switched TMF treatments from week 96 to 144. In subjects switching from TDF to TMF, the non-indexed estimated glomerular filtration rate (by non-indexed CKD-EPI formula) and creatinine clearance (by Cockcroft-Gault formula) were both increased, which were (2.31±8.33) ml/min and (4.24±13.94) ml/min, respectively. These changes were also higher than those in subjects with extending TMF treatment [(0.91±8.06) ml/min and (1.30±13.94) ml/min]. Meanwhile, switching to TMF also led to an increase of the bone mineral density (BMD) by 0.75% in hip and 1.41% in spine. On the other side, a slight change in TC/HDL ratio by 0.16 (IQR: 0.00, 0.43) and an increase in body mass index (BMI) by (0.54±0.98) kg/m 2 were oberved with patients switched to TMF, which were significantly higher than that in TMF group. Conclusion:CHB patients receiving 144 weeks of TMF treatment showed favorable safety profile. After switching to TMF, the bone and renal safety was significantly improved in TDF group, though experienceing change in metabolic parameters and weight gain (NCT03903796).

Objective:To evaluate the outcome of Augmented reality technology in the recognizing of oral and maxillofacial anatomy.Methods:This study was conducted on the undergraduate students in Peking University School of Stomatology who were learning oral and maxillofacial anatomy.The image da-ta were selected according to the experiment content,and the important blood vessels and bone tissue structures,such as upper and lower jaws,neck arteries and veins were reconstructed in 3D(3-dimension-al)by digital software to generate experiment models,and the reconstructed models were encrypted and stored in the cloud.The QR(quick response)code corresponding to the 3D model was scanned by a net-worked mobile device to obtain augmented reality images to assist experimenters in teaching and subjects in recognizing.Augmented reality technology was applied in both the theoretical explanation and cadaveric dissection respectively.Subjects'feedback was collected in the form of a post-class question-naire to evaluate the effectiveness of augmented reality technology-assisted recognizing.Results:In the study,83 undergraduate students were included as subjects in this study.Augmented reality technology could be successfully applied in the recognizing of oral and maxillofacial anatomy.All the subjects could scan the QR code through a connected mobile device to get the 3D anatomy model from the cloud,and zoom in/out/rotate the model on the mobile.Augmented reality technology could provide personalized 3D model,based on learners'needs and abilities.The results of likert scale showed that augmented reality technology was highly recognized by the students(9.19 points),and got high scores in terms of forming a three-dimensional sense and stimulating the enthusiasm for learning(9.01 and 8.85 points respective-ly).Conclusion:Augmented reality technology can realize the three-dimensional visualization of impor-tant structures of oral and maxillofacial anatomy and stimulate students'enthusiasm for learning.Be-sides,it can assist students in building three-dimensional space imagination of the anatomy of oral and maxillofacial area.The application of augmented reality technology achieves favorable effect in the recog-nizing of oral and maxillofacial anatomy.

ObjectiveTo explore the effect and mechanism of Sishenjian on synovial lesions induced by monosodium iodoacetate （MIA） in rats with knee osteoarthritis （KOA）. MethodSixty female Sprague-Dawley （SD） rats were randomly divided into the following six groups： normal group， model group， celecoxib group， and high-， medium-， and low-dose Sishenjian group. The KOA rat model was established by intra-articular injection of MIA. Celecoxib （18 mg·kg^-1） and Sishenjian （14.4， 7.2， 3.6 g·kg^-1） were administered by gavage according to the groups. All rats were euthanized after four weeks of continuous administration. The transverse diameter of the bilateral knee joints of rats was measured， and gross observation of the knee joint was performed. Pathological changes in knee joint synovial tissue were observed by hematoxylin-eosin （HE） staining and picrosirius red staining. Immunohistochemistry （IHC） was used to detect the expression of vascular endothelial growth factor A （VEGFA） in synovial tissue. The levels of inflammatory cytokines in the joint synovial fluid were detected by enzyme-linked immunosorbent assay （ELISA）. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to detect the expression of mRNA and proteins related to the transforming growth factor-β₁ （TGF-β₁）/Smad2/3 pathway in knee joint synovium. ResultCompared with the normal group， the transverse diameter of the knee joint in the model group significantly increased （P<0.01）. Compared with the model group， the transverse diameter of the knee joint in rats of each Sishenjian group significantly decreased （P<0.01）. Compared with the normal group， the expression levels of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in the knee joint synovial fluid of model group significantly increased （P<0.01）. Compared with the model group， the expression levels of IL-1β and TNF-α in the knee joint synovial fluid of rats in each Sishenjian group significantly decreased （P<0.01）. Compared with the normal group， the expression levels of TGF-β₁， Smad2/3， phosphorylation（p）-Smad2/3， type Ⅰ collagen α1 （ColⅠ_α1）， type Ⅲ collagen α1 （ColⅢ_α1）， VEGFA proteins and TGF-β₁， Smad2/3， ColⅠ_α1， ColⅢ_α1 mRNA in knee joint synovium of model group significantly increased （P<0.01）. Compared with the model group， the expression levels of TGF-β₁， Smad2/3， phosphorylation （p）-Smad2/3， ColⅠ_α1， ColⅢ_α1， VEGFA proteins and TGF-β₁， Smad2/3， ColⅠ_α1， ColⅢ_α1 mRNA in knee joint synovium of rats in each Sishenjian group significantly decreased （P<0.05， P<0.01）. ConclusionSishenjian can inhibit synovial inflammation and angiogenesis， and may become a potential drug for treating synovial lesions in KOA by regulating the TGF-β₁/Smad2/3 pathway.

ObjectiveThe glycosidic linkage structural characteristics of polysaccharides from Pinelliae Rhizoma（PR） and its processed products were analyzed by sugar spectrum， high performance thin layer chromatography（HPTLC）， fluorescence-assisted carbohydrate gel electrophoresis（PACE） based on partial acid hydrolysis and specific glycosidase hydrolysis， and the antioxidant activities of polysaccharides before and after hydrolysis（enzymolysis） were compared. MethodPolysaccharides from PR and its processed products were extracted by ultrasound extraction， starch was hydrolyzed by α-amylase， and small molecules below 3 kDa were removed by ultrafiltration. The purified polysaccharides were prepared by hydrolysis of acid and five different specific glycosidases， and the hydrolysates were analyzed by HPTLC and PACE. The antioxidant capacity of polysaccharides was analyzed by 2，2′-azino-bis（3-ethylbenzthiazoline-6-sulfonic acid）（ABTS） and 2，2-diphenyl-1-picrylhydrazyl（DPPH） free radical scavenging experiment before and after different hydrolysis. ResultThrough HPTLC and PACE analysis， it was found that polysaccharides from PR and its processed products could be hydrolyzed by β-galactosidase， β-mannase， cellulase and pectinase， but hardly hydrolyzed by glucanase， indicating that the polysaccharides contained β-galactopyranoside bond， β-1，4-mannoside bond， β-1，4-glucoside bond and α-1，4-galacturonic acid glycosidic bond. In vitro antioxidant experiments showed that the ABTS radical scavenging capacity of the polysaccharides from PR and its processed products was weakened after acid hydrolysis and pectinase enzymatic hydrolysis， while the ABTS radical scavenging capacity was enhanced after enzymatic hydrolysis with cellulase， β-galactosidase， and β-mannase. And after different hydrolysis， the DPPH free radical scavenging capacity of polysaccharides from PR and its processed products was all significantly enhanced. ConclusionThe glycosidic linkage structural characteristics of polysaccharides from PR and its processed products was analyzed by sugar spectrum in this paper， and the relationship between glycosidic bond types and their antioxidant activity was clarified through in vitro antioxidant experiments， which is beneficial for further elucidating the material basis of the related efficacy of PR and its processed products， and providing new ideas and methods for analyzing the structural characteristics of polysaccharides in Chinese medicines.

Objective To explore the clinical efficacy of repeated transcranial magnetic stimulation(rTMS)and acupuncture therapy in the treatment of chronic insomnia disorder(CID)patients.Methods A total of 80 patients with CID,who were treated at Nanchang First Hospital from January 2022 to December 2023,were selected for the study.The patients were randomly divided into control group and treatment group,with 40 cases in each group.The control group patients were treated with dexmedetomidine,while the treatment group patients received rTMS and acupuncture therapy in addition to control group.The treatment course was 4 weeks,and the sleep quality,sleep related indicators,and psychological condition improvement of both groups of patients were observed before and after treatment.Results After treatment,the Pittsburgh sleep quality index scores of both groups of patients decreased(P＜0.05);The sleep latency and number of awakenings were lower than before treatment(P＜0.05),and the total sleep time,sleep efficiency,and proportion of rapid eye movement sleep were higher than before treatment,treatment group showed more significant improvement than control group(P＜0.05).After treatment,the Hamilton anxiety and depression scale scores of both groups of patients decreased compared to before treatment,but there was no statistically significant difference in control group before and after treatment(P＞0.05).However,there was a statistically significant difference in treatment group before and after treatment(P＜0.05).Conclusion The combination of rTMS and acupuncture treatment can significantly improve the sleep quality of CID patients,while also reducing the accompanying symptoms of anxiety and depression.