ObjectiveTo make clear exercise combined with Shenghui Tang interferes in acetylcholine receptor （M1AChR） to improve mitochondrial autophagy and enhance cognition of Alzheimer's disease （AD） model rats through the adenylate activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） signaling pathway. MethodsForty-eight male SD rats of SPF grade were randomly divided into a blank group， a model group， a Shenghui Tang group （9.3 g·kg^-1）， an exercise group， an exercise + Shenghui Tang group （9.3 g·kg^-1）， and a rapamycin group （1.5 mg·kg^-1）. Except for the blank group， the rat model of AD was constructed by injecting amyloid beta （Aβ_1-42） into hippocampus stereotaxically. The exercise group received treadmill exercise for 4 weeks， while the Shenghui Tang group received intragastric administration for 4 weeks， and the exercise + Shenghui Tang group received treadmill exercise and intragastric administration of Shenghui Tang for 4 weeks simultaneously. After the intervention， the Morris water maze test was used to detect the learning and memory ability. Spontaneous behavior was observed in the open field test. The pathological structure of hippocampal neurons was observed by NISSl staining. The expression level of M1AChR in hippocampus was detected by immunohistochemistry （IHC）. The autophagy ultrastructure of hippocampal neurons was observed by transmission electron microscopy. The apoptosis rate was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL）. The expression of Beclin1 and microtubule-associated protein light chain 3β （LC3β） was detected by immunofluorescence （IF）. The protein expression of M1AChR， AMPK， p-AMPK， mTOR， Beclin1， LC3β， and chelate 1 （SQSTM1/p62） in hippocampus was detected by Western blot. ResultsCompared with the blank group， the model group exhibited significantly increased platform escape latency on the fifth day （P<0.01） and significantly decreased activity distance in the target quadrant and times of crossing the platform （P<0.01）. The total movement distance in the open field， the time of movement in the central area， and the average speed obviously decreased （P<0.05）. The arrangement of nerve cells in hippocampus CA1 region was dispersed， and the numbers of Nissl bodies and M1AChR positive cells significantly decreased （P<0.01）. The expression of TUNEL positive cells was significantly increased （P<0.01）. The typical autophagic lysosomal structure decreased. The protein expression of M1AChR， p-AMPK/AMPK， p-mTOR/mTOR， Beclin1， LC3Ⅱ/Ⅰ in hippocampus was significantly decreased （P<0.01）， and the protein expression of p62 was significantly increased （P<0.01）. Compared with the model group， the exercise + Shenghui Tang group exhibited obviously improved space exploration and positioning navigation ability （P<0.05， P<0.01）. The total movement distance in the open field， the time of movement in the central area， and the average speed of movement significantly increased （P<0.01）. The number of Nissl bodies significantly increased （P<0.01）. The number of M1AChR positive cells in hippocampus was significantly increased （P<0.01）. The expression of TUNEL positive cells was significantly decreased （P<0.01）. The protein expression of M1AChR， p-AMPK/AMPK， p-mTOR/mTOR， Beclin1， LC3Ⅱ/Ⅰ in hippocampus was significantly increased （P<0.01）， while the protein expression of p62 was significantly decreased （P<0.01）. Compared with the exercise + Shenghui Tang group， the Shenghui Tang group and the exercise group showed significantly increased platform escape latency on the fifth day （P<0.01） and obviously decreased activity distance in the target quadrant and times of crossing the platform （P<0.05， P<0.01）. The total movement distance in the open field， the time of movement in the central area， and the average speed of movement significantly decreased （P<0.01）. The number of Nissl bodies and the number of M1AChR positive cells significantly decreased （P<0.01）. The expression of TUNEL positive cells was obviously increased （P<0.05）. Ultrastructure of the hippocampal region showed decreased autophagy level. The protein expression of M1AChR， p-AMPK/AMPK， p-mTOR/mTOR， LC3Ⅱ/Ⅰ in the hippocampus was obviously decreased in the Shenghui Tang group （P<0.05， P<0.01）， while the protein expression of p62 was significantly increased （P<0.01）. In the exercise group， the protein expression of M1AChR， p-AMPK/AMPK， Beclin1， and LC3Ⅱ/Ⅰ was obviously decreased （P<0.05， P<0.01）， while the protein expression of p-mTOR/mTOR and p62 was significantly increased （P<0.01）. ConclusionExercise combined with traditional Chinese medicine can enhance the expression of M1AChR in the hippocampus of AD model rats， induce autophagy through the AMPK/mTOR signaling pathway， and improve the learning and memory ability of AD rats.

Aim To systematically elucidate the molecular regulatory network of thermogenic function in brown adipose tissue(BAT)through multi-omics integrative analysis,to discover novel thermogenic regulatory genes and provide novel therapeutic targets for metabolic disorders.Methods A novel methodology for screening key genes regulating thermogenesis in BAT was constructed:First,differential expression analysis was performed on bulk RNA-seq data from murine BAT.Genes meeting the thresholds of ABS(log2FoldChange)＞1 and Padj＜0.05 were identified as differentially expressed genes.Intersectional analysis was then applied to obtain consensus upregulated and downregulated gene sets.Subsequently,scRNA-seq data of brown adipocytes were partitioned into high-expression group and low-expression group based on the expression levels of candidate genes.Differential analysis and gene set enrichment analysis(GSEA)were conducted between these groups to assess the correlation between candidate genes and thermogenic function.Finally,ex-perimental validation of selected candidate genes was performed using quantitative real-time PCR and Western blot.Results Bioinformatics analysis identified 65 thermogenesis-positive correlated genes and 7 thermogenesis-negative corre-lated genes.Subsequent quantitative PCR validation demonstrated that candidate genes Mfsd2a,Me1,Slc25a34,Pfkp,Ankrd9,Hsd17b12,Aldoa,Ctsz and Pcyt2 exhibited upregulation exceeding 5-fold,while Pid1 and Angpt1 showed down-regulation over 50％.All observed expression changes demonstrated statistical significance(P＜0.01)through rigorous hypothesis testing.These findings highlight the potential involvement of these genes in thermogenic regulation,warranting further functional investigations to elucidate their molecular mechanisms in energy metabolism pathways.Conclusions This study established a novel"computational screening → in silico knockout → experimental validation"paradigm for tar-get discovery,systematically unveiling the molecular network involved in BAT thermogenic regulation.This methodology is equally applicable for identifying key regulatory genes in other physiological or pathological processes.The study identi-fied 11 core genes that may play pivotal regulatory roles during BAT thermogenic activation,which could potentially offer novel pharmacological intervention targets to improve energy metabolism and treat obesity-related complications.

Aim To systematically elucidate the molecular regulatory network of thermogenic function in brown adipose tissue(BAT)through multi-omics integrative analysis,to discover novel thermogenic regulatory genes and provide novel therapeutic targets for metabolic disorders.Methods A novel methodology for screening key genes regulating thermogenesis in BAT was constructed:First,differential expression analysis was performed on bulk RNA-seq data from murine BAT.Genes meeting the thresholds of ABS(log2FoldChange)＞1 and Padj＜0.05 were identified as differentially expressed genes.Intersectional analysis was then applied to obtain consensus upregulated and downregulated gene sets.Subsequently,scRNA-seq data of brown adipocytes were partitioned into high-expression group and low-expression group based on the expression levels of candidate genes.Differential analysis and gene set enrichment analysis(GSEA)were conducted between these groups to assess the correlation between candidate genes and thermogenic function.Finally,ex-perimental validation of selected candidate genes was performed using quantitative real-time PCR and Western blot.Results Bioinformatics analysis identified 65 thermogenesis-positive correlated genes and 7 thermogenesis-negative corre-lated genes.Subsequent quantitative PCR validation demonstrated that candidate genes Mfsd2a,Me1,Slc25a34,Pfkp,Ankrd9,Hsd17b12,Aldoa,Ctsz and Pcyt2 exhibited upregulation exceeding 5-fold,while Pid1 and Angpt1 showed down-regulation over 50％.All observed expression changes demonstrated statistical significance(P＜0.01)through rigorous hypothesis testing.These findings highlight the potential involvement of these genes in thermogenic regulation,warranting further functional investigations to elucidate their molecular mechanisms in energy metabolism pathways.Conclusions This study established a novel"computational screening → in silico knockout → experimental validation"paradigm for tar-get discovery,systematically unveiling the molecular network involved in BAT thermogenic regulation.This methodology is equally applicable for identifying key regulatory genes in other physiological or pathological processes.The study identi-fied 11 core genes that may play pivotal regulatory roles during BAT thermogenic activation,which could potentially offer novel pharmacological intervention targets to improve energy metabolism and treat obesity-related complications.

OBJECTIVE To investigate the effects of parthenolide （PLT） on systemic inflammation and intestinal injury in rats with acute pancreatitis （AP） by regulating the Kelch-like epichlorohydrin-associated protein 1 （Keap1）/nuclear factor-erythroid-2 related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） signaling pathway. METHODS AP rat model was established by injecting 3.5% sodium taurine cholate solution （1 mL/kg） into the biliary pancreatic duct， and modeled rats were divided into AP group， PLT （300 µg/kg） group， dexamethasone （2 mg/kg） group， inhibitor （11 mg/kg Nrf2 inhibitor ML385） group， and PLT+inhibitor group （300 µg/kg PLT+11 mg/kg ML385）， with 10 rats in each group. Another 10 rats were taken as a sham operation group. Each group was given relevant medicine or normal saline via tail vein/intraperitoneal injection once. After 24 h， serum lipase and amylase levels， the levels of oxidative stress index [superoxide dismutase （SOD） and malondialdehyde （MDA）] and inflammatory factors [interleukin-1β （IL-1β）， IL-6 and tumor necrosis factor-α （TNF-α）] were detected. The histopathological changes in colon mucosa and pancreas were observed， and Chiu and Schmidt scores were performed. The cell apoptosis in colon mucosa and the protein expressions of Keap1， Nrf2 and HO-1 were detected. RESULTS Compared with the sham operation group， there was obvious inflammatory cell infiltration in colon mucosa and pancreatic tissue， cell shedding or tissue necrosis and severe bleeding； serum levels of lipase， amylase， MDA， IL-1β， IL-6 and TNF-α， Chiu and Schmidt scores， apoptotic rate and protein expression of Keap1 in colonic mucosa were significantly increased or up-regulated， while SOD level and protein expressions of Nrf2 20230993） and HO-1 were decreased or down-regulated significantly （P＜0.05）. Compared with the AP group， the above indexes in the PLT group and dexamethasone group were significantly improved， while those in the inhibitor group further deteriorated （P＜0.05）. Inhibitor could significantly reverse the improvement effect of PLT on the above indexes in AP rats （P＜ 0.05）. CONCLUSIONS PLT inhibits inflammation and oxidative stress in AP rats， alleviates intestinal damage， and its mechanism may be related to inhibiting protein expression of Keap1 and activating Nrf2/HO-1 signaling pathway.

Objective:To investigate the phenomenon of hippocampal ferroptosis and its change in a rat model of chronic constriction injury(CCI)of the sciatic nerve,as well as the association between hippocampal ferroptosis and emotional disorders induced by neuro-pathic pain.Methods:A total of 32 male Sprague-Dawley rats were randomly divided into Sham group,CCI group,CCI+F group,and CCI+E group,with 8 rats in each group.The rats in the CCI+F group and the CCI+E group were given intraperitoneal injection of Ferrostatin-1(10 mg/kg)and Erastin(10 mg/kg),respectively,since day 7 after surgery for two consecutive days.Mechanical with-drawal threshold(MWT),paw withdrawal latency(PWL),and open field test(OFT)were measured before surgery and on days 7 and 14 after surgery.On day 14 after surgery,the rats were sacrificed to col-lect hippocampal tissue;Western blot was used to measure the levels of GPX4,xCT,and FTH1;related kits were used to measure the expression levels of MDA and GSH;HE staining,Nissl staining,and immunofluorescent staining were performed;transmission electron microscopy was used to observe the structural changes of the mito-chondria.Results:In terms of behavioristics,compared with the Sham group,the CCI group had significant reductions in MWT and PWL on day 7 after surgery(P<0.001),with further reductions from day 7 to day 14 after surgery(P<0.001);compared with the CCI group,the CCI+F group had significant increases in MWT and PWL on day 14 after surgery(P<0.001),and the CCI+E group had no significant change in MWT and a significant reduction in PWL(P<0.01).In terms of the OFT test,compared with the Sham group,the CCI group had significant reductions in total distance and number of central squares crossed(P<0.001)and a significant increase in immobility time(P<0.001);compared with the CCI group,the CCI+F group had significant increases in total distance and number of central squares crossed and a significant reduction in immobility time,while the CCI+E group had no significant changes in these indi-ces.In terms of biochemical results,compared with the Sham group,the CCI group had significant reductions in GPX4,xCT,and FTH1(P<0.01),a significant increase in MDA,and a significant reduction in GSH;compared with the CCI group,the CCI+F group had sig-nificant increases in GPX4,xCT,and FTH1(P<0.05),a significant reduction in MDA(P<0.001),and a significant increase in GSH(P<0.01),and the CCI+E group had significant reductions in xCT and FTH1,with no significant changes in MDA and GSH.In terms of morphology,compared with the Sham group,the CCI group had damage and necrosis of hippocampal neurons,significant reductions in Nissl bodies and c-Fos level(P<0.05),and significantly damaged mitochondrial cristae on day 14 after surgery;compared with the CCI group,the CCI+F group had intact structures of hippocampal neurons,significant increases in Nissl bodies and c-Fos(P<0.05),and relatively intact mitochondria,while there were no significant differences in c-Fos and Nissl bodies between the CCI+E group and the CCI group.The pairwise linear correlation analysis of PWL,MWT,GPX4,OFT,and c-Fos on day 14 after surgery showed a signifi-cantly positive correlation between any two indicators(P<0.01).Conclusion:Peripheral nerve injury triggers ferroptosis in the hippo-campus and causes anxiety and depression,thereby aggravating ferroptosis and accelerating the development of central hyperalgesia.

Recent studies have indicated that the expression of ubiquitin-specific protease 51 (USP51), a novel deubiquitinating enzyme (DUB) that mediates protein degradation as part of the ubiquitin‒proteasome system (UPS), is associated with tumor progression and therapeutic resistance in multiple malignancies. However, the underlying mechanisms and signaling networks involved in USP51-mediated regulation of malignant phenotypes remain largely unknown. The present study provides evidence of USP51's functions as the prominent DUB in chemoresistant triple-negative breast cancer (TNBC) cells. At the molecular level, ectopic expression of USP51 stabilized the 78 kDa Glucose-Regulated Protein (GRP78) protein through deubiquitination, thereby increasing its expression and localization on the cell surface. Furthermore, the upregulation of cell surface GRP78 increased the activity of ATP binding cassette subfamily B member 1 (ABCB1), the main efflux pump of doxorubicin (DOX), ultimately decreasing its accumulation in TNBC cells and promoting the development of drug resistance both in vitro and in vivo. Clinically, we found significant correlations among USP51, GRP78, and ABCB1 expression in TNBC patients with chemoresistance. Elevated USP51, GRP78, and ABCB1 levels were also strongly associated with a poor patient prognosis. Importantly, we revealed an alternative intervention for specific pharmacological targeting of USP51 for TNBC cell chemosensitization. In conclusion, these findings collectively indicate that the USP51/GRP78/ABCB1 network is a key contributor to the malignant progression and chemotherapeutic resistance of TNBC cells, underscoring the pivotal role of USP51 as a novel therapeutic target for cancer management.

Objective:To investigate the efficacy of 3D-Slicer printed guide-assisted percutaneous balloon compression (PBC) of the trigeminal ganglion in the treatment of trigeminal neuralgia (TN).Methods:A total of 100 patients with TN admitted to the Department of Neurosurgery at the People′s Hospital of Fuyang from June 2022 to June 2024 were selected and randomly divided into a control group and a study group, with 50 patients in each group. The control group underwent conventional PBC, while the study group received 3D-Slicer printed guide-assisted PBC. The two groups were compared in terms of operation time, number of punctures, puncture time, number of mobile X-ray exposures, first-attempt success rate, immediate postoperative Barrow Neurological Institute (BNI) pain intensity score, and incidence of complications.Results:The study group showed significantly shorter operation time, fewer punctures, shorter puncture time, and fewer mobile X-ray exposures compared to the control group (all P<0.05). The first-attempt success rate was also higher in the study group ( P<0.05). There were no significant differences in the postoperative BNI pain intensity scores or complication rates between the two groups (all P>0.05). Conclusions:3D-Slicer printed guide-assisted PBC for TN significantly shortens operation and puncture time, reduces the number of punctures and mobile X-ray exposures, and improves the first-attempt success rate, making it worthy of clinical promotion and application.

Objective:To investigate the efficacy of 3D-Slicer printed guide-assisted percutaneous balloon compression (PBC) of the trigeminal ganglion in the treatment of trigeminal neuralgia (TN).Methods:A total of 100 patients with TN admitted to the Department of Neurosurgery at the People′s Hospital of Fuyang from June 2022 to June 2024 were selected and randomly divided into a control group and a study group, with 50 patients in each group. The control group underwent conventional PBC, while the study group received 3D-Slicer printed guide-assisted PBC. The two groups were compared in terms of operation time, number of punctures, puncture time, number of mobile X-ray exposures, first-attempt success rate, immediate postoperative Barrow Neurological Institute (BNI) pain intensity score, and incidence of complications.Results:The study group showed significantly shorter operation time, fewer punctures, shorter puncture time, and fewer mobile X-ray exposures compared to the control group (all P<0.05). The first-attempt success rate was also higher in the study group ( P<0.05). There were no significant differences in the postoperative BNI pain intensity scores or complication rates between the two groups (all P>0.05). Conclusions:3D-Slicer printed guide-assisted PBC for TN significantly shortens operation and puncture time, reduces the number of punctures and mobile X-ray exposures, and improves the first-attempt success rate, making it worthy of clinical promotion and application.

Objective To evaluate the analgesic effects of ultrasound-guided hip capsule block and fascia iliaca block in elderly patients undergoing hip replacement surgery and their impacts on postoperative rehabilitation.Methods A total of 44 patients who underwent total hip replacement in the Second Affiliated Hospital of Wenzhou Medical University from May to December in 2023 were selected and divided into fascia iliaca block group(group F)and hip capsule block group(group H)according to the random number table,with 22 cases in each group.All patients were anesthetized by lumbar anesthesia combined with nerve block.The primary indicators included the recovery of lower limb muscle strength at 8h,24h,48h after operation and the rest and movement visual analogue scale(VAS)scores at each observation point.The secondary indicators were sufentanil consumption of analgesic pump,the number of compressions,the use rates of additional parecoxib sodium in ward,the length of hospital stay and the occurrence of adverse reactions.Results The recovery of lower limb muscle strength in group H was better than that in group F at 8h and 24h after operation,and the difference was statistically significant(P<0.05).The rest and movement VAS scores at 30min after block and 4h after operation in group H were significantly lower than those in group F(P<0.05),while there were no significant differences in the rest and movement VAS scores between two groups at other time points(P>0.05).The rest and movement VAS scores at each time point after blockade were lower than those before blockade in two groups(P<0.05).The sufentanil consumption in analgesic pump and the number of compressions in group H was lower than that in group F at 4h after operation(P<0.05),and there were no significant differences in analgesic pump data and the use rates of parecoxib sodium between two groups at subsequent time points(P>0.05).There were no statistically significant difference in the incidence of nausea within 48h after operation and hospital stay between two groups(P>0.05).Conclusion Both fascia iliaca block and hip capsule block can be safely and effectively used in elderly patients with hip replacement,but the analgesic effect of hip capsule block is faster,the early postoperative analgesic effect is better,and the impact on lower limb movement is less.

Objective:To analyze the effects of exposure to life events and social support levels during different stages of pregnancy on low birth weight in offspring.Methods:From 2021 to 2023, pregnant women in early pregnancy who were registered with health cards in Linping District, Hangzhou City, were recruited and followed up. The Life Events Scale for Pregnant Women (LESPW) and Social Support Rating Scale (SSRS) were used to evaluate the exposure to life events and social support levels of pregnant women in early, middle and late pregnancy, respectively. A generalized linear model was used to analyze the impact and critical period of exposure to prenatal life events and social support levels on the risk of low birth weight in offspring.Results:A total of 3 663 pregnant women with ages M ( Q1, Q3) of 29.18 (26.59, 32.21) years were included in this study. 116 cases (3.17%) of infants with low birth weight were delivered. Generalized linear model analysis showed no correlation between the level of social support in early, middle and late pregnancy and low birth weight in offspring (all P>0.05). The risk of low birth weight in offspring of pregnant women with high exposure to early pregnancy life events was 1.78 times higher than that of the low exposure group ( RR=1.78, 95% CI: 1.13-2.73, P=0.010), and there was no association in the middle and late stages of pregnancy (both P>0.05). Pregnant women with high exposure to early life events and low levels of social support had a 2.08-fold higher risk of low birth weight in their offspring compared to the low exposure group ( RR=2.08, 95% CI: 1.17-6.78, P=0.010), while this situation was not associated with high social support stratification. Conclusion:Exposure to life events during pregnancy has an early window effect on birth weight. Increased exposure to life events during early pregnancy is associated with a higher risk of low birth weight in offspring. This association is more pronounced in pregnant women with low social support.