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 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 explore the intervention effects of the skill training for parents with autism child (STPAC) on toddlers with autism spectrum disorder (ASD).Methods:A multicenter non-randomized concurrent controlled study design was conducted. Thirty children with ASD aged 15-30 months, first diagnosed at the Children′s Hospital of Fudan University, the First Hospital of Jilin University, and Chengdu Women′s and Children′s Central Hospital from 2019 to 2020, were enrolled in the STPAC group. Thirty children with ASD who visited the same hospitals during the same period but refused the STPAC intervention were selected as the control group. The STPAC group received an 8-week intervention (3 h/week) followed by quarterly follow-ups for 1 year, while the control group voluntarily chose community-based routine interventions. The Griffiths development scales-Chinese (GDS-C) was used to assess the developmental levels, and the communication and symbolic behavior scales developmental profile infant-toddler checklist (CSBS-DP-ITC) was completed by the primary caregivers to evaluate social, language and symbolic behavior. The independent samples t-tests or Mann-Whitney U tests, etc.was used for inter-group comparison. The paired t-tests or Wilcoxon signed-rank tests, etc. was used for inter-group pre-post intervention comparison. Results:The STPAC group included 30 children (22 males and 8 females, aged (23.9±2.2) months), and the control group included 30 children (20 males and 10 females, aged (24.2±2.6) months). Before the intervention, there were no statistically differences in GDS-C development quotient (DQ) and CSBS-DP-ITC scores between groups (all P>0.05). After 1-year intervention, GDS-C DQ in personal-social, hearing-language, hand-eye coordination, performance domains of STPAC group and GDS-C DQ in personal-social, hearing-language domains of control group were all increased (all P<0.01). After 1-year intervention, CSBS-DP-ITC scores of both groups were all improved in socia, language, symbolic behavior, and total scores (all P<0.001). GDS-C DQ changes before and after 1 year of intervention in hearing-language, hand-eye coordination, performance domains of the STPAC group were all higher the those of control group (34(15, 48 vs. 10(-4, 39), 11±20 vs. -1±19, 23±25 vs. 8±22, all P<0.05). CSBS-DP-ITC scores changes before and after 1 year of intervention in social and total scores of the STPAC group were both higher the those of control group (10(5, 30) vs. 3(1, 7), 26±17 vs. 11±8, both P<0.001). Conclusion:Compared with the community routine interventions, the STPAC better improves the language, hand-eye coordination, visual-spatial, social communication, and play skills in ASD toddlers.

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.

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 explore the intervention effects of the skill training for parents with autism child (STPAC) on toddlers with autism spectrum disorder (ASD).Methods:A multicenter non-randomized concurrent controlled study design was conducted. Thirty children with ASD aged 15-30 months, first diagnosed at the Children′s Hospital of Fudan University, the First Hospital of Jilin University, and Chengdu Women′s and Children′s Central Hospital from 2019 to 2020, were enrolled in the STPAC group. Thirty children with ASD who visited the same hospitals during the same period but refused the STPAC intervention were selected as the control group. The STPAC group received an 8-week intervention (3 h/week) followed by quarterly follow-ups for 1 year, while the control group voluntarily chose community-based routine interventions. The Griffiths development scales-Chinese (GDS-C) was used to assess the developmental levels, and the communication and symbolic behavior scales developmental profile infant-toddler checklist (CSBS-DP-ITC) was completed by the primary caregivers to evaluate social, language and symbolic behavior. The independent samples t-tests or Mann-Whitney U tests, etc.was used for inter-group comparison. The paired t-tests or Wilcoxon signed-rank tests, etc. was used for inter-group pre-post intervention comparison. Results:The STPAC group included 30 children (22 males and 8 females, aged (23.9±2.2) months), and the control group included 30 children (20 males and 10 females, aged (24.2±2.6) months). Before the intervention, there were no statistically differences in GDS-C development quotient (DQ) and CSBS-DP-ITC scores between groups (all P>0.05). After 1-year intervention, GDS-C DQ in personal-social, hearing-language, hand-eye coordination, performance domains of STPAC group and GDS-C DQ in personal-social, hearing-language domains of control group were all increased (all P<0.01). After 1-year intervention, CSBS-DP-ITC scores of both groups were all improved in socia, language, symbolic behavior, and total scores (all P<0.001). GDS-C DQ changes before and after 1 year of intervention in hearing-language, hand-eye coordination, performance domains of the STPAC group were all higher the those of control group (34(15, 48 vs. 10(-4, 39), 11±20 vs. -1±19, 23±25 vs. 8±22, all P<0.05). CSBS-DP-ITC scores changes before and after 1 year of intervention in social and total scores of the STPAC group were both higher the those of control group (10(5, 30) vs. 3(1, 7), 26±17 vs. 11±8, both P<0.001). Conclusion:Compared with the community routine interventions, the STPAC better improves the language, hand-eye coordination, visual-spatial, social communication, and play skills in ASD toddlers.

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 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.