Objective To explore the role and mechanism of mechanically sensitive ion channel Piezo2 in mechanical allodynia of rats with low back pain induced by simulating the low-frequency vibration of a helicopter.Methods Low-frequency vibration(LFV)model with 3-dimensional 6 degrees of freedom was used to induce low back pain in awake rats in a sitting position.Twenty-four male SD rats(8 weeks old)were randomly divided into control(Ctrl)group and LFV group.HE staining was used to evaluate the injury of the multifidus muscle.Von Frey test was carried out to detect pain sensitivity.Open field test was employed to assess the spontaneous activity and anxiety.ELISA,Western blotting and immunofluorescence staining were performed to detect the expression of NGF,TrkA and downstream molecule Piezo2.Dorsal root ganglia(DRG)neurons was isolated from SD rats and primarily cultured.After identified with immunofluorescence staining,the neurons were divided into the Ctrl group,the LFV group,and the LFV+D-GsMTx4(D-G4,an Piezo2 channel antagonist)group.Western blotting was used to detect the protein expression of Piezo2,and a calcium ion fluorescent probe was utilized to detect the intracellular Ca2+.The DRG neurons were pretreated with 50 ng/mL NGF for 1 h.Calcium ion fluorescent probe was used to observe the changes in intracellular Ca2+in the LFV group,the LFV+NGF group,and the LFV+NGF+D-G4 group.Results The rats of the LFV group showed abnormal morphology in multifidus muscles,accompanied with inflammatory cell infiltration,decreased paw withdrawal reflex threshold(P<0.05),and shortened total active time and active time in the centre,and decreased distance traveled in the centre(P<0.05),while prolonged total stationary time,stationary time in the periphery,and increased distance traveled in the periphery(P<0.05),and moreover,enhanced expression of Piezo2,NGF and TrkA in the DRG tissues(P<0.05).Cell experiments showed that compared with the Ctrl group,the expression of Piezo2 in the neurons was increased(P<0.05),and the intracellular Ca2+level was significantly elevated in the LFV group(P<0.05).Compared with the LFV group,the Ca2+level was higher in the LFV+NGF group(P<0.05),and the sensitization effect of NGF on Piezo2 was reversed after D-G4 treatment(P<0.05).Conclusion Sustained low-frequency vibration induces low back pain and mechanical allodynia in rats through the NGF-TrkA/Piezo2 pathway.

ObjectiveTo investigate the intervention effects of Suanzaoren Tang on depression model rats induced by isolation combined with chronic unpredictable mild stress （CUMS）， and to examine its influence on the c-Jun N-terminal kinase （JNK）/proto-oncogene protein （c-Myc）/tumor suppressor protein 53 （p53） signaling pathway， thereby revealing its potential functional mechanism. MethodsA total of 72 male SD rats were randomly divided into six groups using a strict random number table： blank group， model group， fluoxetine group （3.6 mg·kg^-1）， and high-， medium-， and low-dose Suanzaoren Tang groups （10， 5， 2.5 g·kg^-1），with 12 rats in each group. A depression model was established using isolation combined with CUMS. Fluoxetine and different doses of Suanzaoren Tang were administered continuously for 28 days. Behavioral indicators such as sucrose water consumption and open field test scores were recorded. Western blot and immunohistochemistry （IHC） were employed to analyze the expression of key proteins in the JNK/c-Myc/p53 signaling pathway， and the terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） assay was used to evaluate the number of apoptotic cells in the hippocampus. ResultsCompared with the blank group， the model group exhibited a significantly reduced sucrose preference index （P<0.01）， a lower total score of horizontal and vertical movements in the open field test （P<0.01）， significantly increased expression of JNK， c-Myc， and p53 proteins in the hippocampus （P<0.01）， and a higher number of TUNEL-positive cells in the hippocampus （P<0.01）. Compared with the model group， the sucrose preference index and the total score of horizontal and vertical movements in the open field test significantly increased in the high- and medium-dose Suanzaoren Tang groups and the fluoxetine group （P<0.05， P<0.01）. The expression of JNK， c-Myc， and p53 proteins significantly decreased in all Suanzaoren Tang groups （high， medium， and low doses） and the fluoxetine group （P<0.05， P<0.01）. The number of TUNEL-positive cells in the hippocampus also significantly decreased in these groups （P<0.01）. ConclusionSuanzaoren Tang can regulate the expression of JNK/c-Myc/p53 proteins in the hippocampus of depression model rats， and its antidepressant mechanism may be related to its protective effect on hippocampal neurons.

Autophagy, a highly conserved cellular degradation mechanism, maintains intracellular homeostasis by removing damaged organelles and abnormal proteins. Its dysregulation is closely associated with various diseases. Autophagy-related protein 12 (ATG12), a core member of the ubiquitin-like protein family, covalently binds to ATG5 through a ubiquitin-like conjugation system to form the ATG12-ATG5-ATG16L1 complex. This complex directly regulates the formation and maturation of autophagosomes, making ATG12 a key molecule in the initiation of autophagy. Recent studies have revealed that ATG12 functions extend far beyond the classical autophagy context. It promotes apoptosis by binding to anti-apoptotic proteins of the Bcl-2 family (e.g., Bcl-2 and Mcl-1) and enhances host antiviral immunity by regulating the NF-κB and interferon signaling pathways. Moreover, ATG12 deficiency can lead to mitochondrial biogenesis impairment, energy metabolism disorders, and substrate-dependent metabolic shifts, underscoring its pivotal role in cellular metabolic homeostasis. At the disease level, dysregulation of ATG12 expression is closely linked to tumorigenesis and cancer progression. By modulating the dynamic balance between autophagy and apoptosis, ATG12 influences cancer cell proliferation, metastasis, and chemoresistance. Notably, ATG12 is abnormally overexpressed in multiple cancers, including breast, liver, and gastric cancer, highlighting its potential as a therapeutic target. Furthermore, in neurodegenerative diseases such as Parkinson’s disease, ATG12 mitigates protein toxicity by enhancing mitochondrial autophagy. In cardiovascular diseases, it alleviates ischemia-reperfusion injury by regulating cardiomyocyte autophagy and apoptosis, demonstrating its broad regulatory role across various pathological conditions. Genetic studies further underscore the clinical significance of ATG12. Polymorphisms in the ATG12 gene (e.g., rs26537 and rs26538) have been significantly associated with the risk of head and neck squamous cell carcinoma, hepatocellular carcinoma, and atrophic gastritis. Notably, the risk allele of rs26537 enhances ATG12 promoter activity, leading to its overexpression and promoting tumorigenesis. These findings provide a molecular basis for individualized risk assessment and targeted interventions based on ATG12 genotype. Despite significant progress, many aspects of ATG12 biology remain unclear. The precise regulatory mechanisms of its post-translational modifications (e.g., ubiquitination and acetylation) are yet to be fully elucidated. Additionally, the molecular pathways underlying its non-canonical functions, such as metabolic regulation and immune modulation, require further investigation. Moreover, the functional heterogeneity of ATG12 in different tumor microenvironments and its role in drug resistance warrant in-depth exploration. Future research should integrate advanced technologies such as cryo-electron microscopy, single-cell sequencing, and organoid models to decipher the intricate regulatory network of ATG12. Additionally, developing small-molecule inhibitors or gene-editing tools targeting its protein interaction interfaces (e.g., the ATG12-ATG3 binding domain) may help overcome current therapeutic challenges. Through interdisciplinary collaboration and clinical translation, ATG12 holds promise as a next-generation molecular target for precision intervention in autophagy-related diseases. This review summarizes the structure and function of ATG12, its role in autophagy initiation, its physiological functions, and its involvement in disease pathogenesis. Furthermore, it discusses future research directions and potential challenges, emphasizing ATG12’s potential as a biomarker and therapeutic target in autophagy-related diseases.

Objective To analyze the applicability of Berg Balance Scale(BBS)in the balance assessment of Parkinson's disease(PD)patients with balancing instrument test as the standard,so as to formulate targeted intervention programs accordingly.Methods A total of 186 patients with PD admitted to Department of Neurology and Department of Rehabilitation Medicine,Huashan Hospital,Fudan University from Jan 2020 to Sep 2022 were selected as the research objects.The static balance function of the patients was evaluated by balancing instrument.The balance function parameters were analyzed according to BBS and levodopa equivalent dose.Results The drug dose did not affect the score of balance instrument.There was a good correlation between BBS and balance instrument.The higher the scale score,the lower the balance instrument score(r=-0.333,P<0.001).There was a positive correlation between levodopa equivalent dose and item 11 of BBS in subjects with BBS total score of 21-40(r=0.715,P=0.046).There was a significant negative correlation between levodopa equivalent dose and item 6 of BBS in subjects with BBS total score of 51-56(r=-0.300,P=0.001).The number of people who lost the most points in BBS from large to small was item 14 of standing on one leg(134 cases),item 13 of standing without support with one foot in front(122 cases),item 11 of turning 360 degrees(75 cases),item 8 of reaching forward with outstretched arms(70 cases),and item 12 of placing one feet alternately on a step or a stool(56 cases).Conclusion In the absence of balancing instrument,BBS has good clinical applicability in the evaluation of PD patients,and some items can be focused on according to the lost points.

Objective:To explore the potential mechanism of action of Xian Fang Huo Ming Yin modified formula(XFHMY)in the treatment of medication-related osteonecrosis of the jaw(MRONJ)through bioinformatics analysis and in vitro and in vivo experiments.Methods:Firstly,the efficacy of XFHMY was evaluated by establishing a mice model of MRONJ induced by zoledronic acid(ZOL);Subsequently,the potential molecular mechanism of XFHMY in the treatment of MRONJ was predicted by using network pharmacology;Lastly,the network pharmacology prediction results were collectively validated through MC3T3-E1 cell proliferation and differentiation experiments,Western blot analysis,and immunohistochemical staining of mouse maxillary bone tissue.Results:Animal experiments showed that,compared to the model group,the XFHMY group exhibited significantly improved wound healing in the tooth extraction socket(P＜0.001),a significant reduction in bone volume fraction and empty lacunae rate in the maxilla(P＜0.0001,P＜0.001),and a significant increase in trabecular separation and osteoclast number(P＜0.01,P＜0.05).Network pharmacology analysis identified 59 common targets,with both GO and KEGG analyses indicating the Wnt/β-catenin signaling pathway as a crucial mechanism for XFHMY in treating MRONJ.Ten key active components,including quercetin,luteolin,and fisetin,were screened,and these compounds demonstrated strong binding affinity with CTNNB1,a core target of this pathway.In vitro experiments revealed that XFHMY(0.25,0.5,1,2,4 mg/mL)promoted MC3T3-E1 cell proliferation(P＜0.0001)and activated the Wnt/β-catenin pathway by upregulating β-catenin and Runx2 protein expression,thereby reversing ZOL-induced inhibition of MC3T3-E1 cell proliferation and differentiation while enhancing both processes.Immunohistochemical analysis of mouse maxillae showed that,compared to the model group,the XFHMY group had significantly increased β-catenin and Runx2 protein expression(P＜0.05,P＜0.01),consistent with the in vitro findings.Conclusion:XFHMY promotes the proliferation and differentiation of osteoblasts through activating the Wnt/β-catenin signaling pathway,which in turn attenuates MRONJ.The novel pharmacological mechanism proposed in this study provides a theoretical basis for the clinical application of XFHMY.

Objective To analyze the applicability of Berg Balance Scale(BBS)in the balance assessment of Parkinson's disease(PD)patients with balancing instrument test as the standard,so as to formulate targeted intervention programs accordingly.Methods A total of 186 patients with PD admitted to Department of Neurology and Department of Rehabilitation Medicine,Huashan Hospital,Fudan University from Jan 2020 to Sep 2022 were selected as the research objects.The static balance function of the patients was evaluated by balancing instrument.The balance function parameters were analyzed according to BBS and levodopa equivalent dose.Results The drug dose did not affect the score of balance instrument.There was a good correlation between BBS and balance instrument.The higher the scale score,the lower the balance instrument score(r=-0.333,P<0.001).There was a positive correlation between levodopa equivalent dose and item 11 of BBS in subjects with BBS total score of 21-40(r=0.715,P=0.046).There was a significant negative correlation between levodopa equivalent dose and item 6 of BBS in subjects with BBS total score of 51-56(r=-0.300,P=0.001).The number of people who lost the most points in BBS from large to small was item 14 of standing on one leg(134 cases),item 13 of standing without support with one foot in front(122 cases),item 11 of turning 360 degrees(75 cases),item 8 of reaching forward with outstretched arms(70 cases),and item 12 of placing one feet alternately on a step or a stool(56 cases).Conclusion In the absence of balancing instrument,BBS has good clinical applicability in the evaluation of PD patients,and some items can be focused on according to the lost points.

Objective:To explore the potential mechanism of action of Xian Fang Huo Ming Yin modified formula(XFHMY)in the treatment of medication-related osteonecrosis of the jaw(MRONJ)through bioinformatics analysis and in vitro and in vivo experiments.Methods:Firstly,the efficacy of XFHMY was evaluated by establishing a mice model of MRONJ induced by zoledronic acid(ZOL);Subsequently,the potential molecular mechanism of XFHMY in the treatment of MRONJ was predicted by using network pharmacology;Lastly,the network pharmacology prediction results were collectively validated through MC3T3-E1 cell proliferation and differentiation experiments,Western blot analysis,and immunohistochemical staining of mouse maxillary bone tissue.Results:Animal experiments showed that,compared to the model group,the XFHMY group exhibited significantly improved wound healing in the tooth extraction socket(P＜0.001),a significant reduction in bone volume fraction and empty lacunae rate in the maxilla(P＜0.0001,P＜0.001),and a significant increase in trabecular separation and osteoclast number(P＜0.01,P＜0.05).Network pharmacology analysis identified 59 common targets,with both GO and KEGG analyses indicating the Wnt/β-catenin signaling pathway as a crucial mechanism for XFHMY in treating MRONJ.Ten key active components,including quercetin,luteolin,and fisetin,were screened,and these compounds demonstrated strong binding affinity with CTNNB1,a core target of this pathway.In vitro experiments revealed that XFHMY(0.25,0.5,1,2,4 mg/mL)promoted MC3T3-E1 cell proliferation(P＜0.0001)and activated the Wnt/β-catenin pathway by upregulating β-catenin and Runx2 protein expression,thereby reversing ZOL-induced inhibition of MC3T3-E1 cell proliferation and differentiation while enhancing both processes.Immunohistochemical analysis of mouse maxillae showed that,compared to the model group,the XFHMY group had significantly increased β-catenin and Runx2 protein expression(P＜0.05,P＜0.01),consistent with the in vitro findings.Conclusion:XFHMY promotes the proliferation and differentiation of osteoblasts through activating the Wnt/β-catenin signaling pathway,which in turn attenuates MRONJ.The novel pharmacological mechanism proposed in this study provides a theoretical basis for the clinical application of XFHMY.

Background::Risk assessment and treatment stratification for three-vessel coronary disease (TVD) remain challenging. This study aimed to investigate the prognostic value of left atrial volume index (LAVI) with the Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score II, and its association with the long-term prognosis after three strategies (percutaneous coronary intervention [PCI], coronary artery bypass grafting [CABG], and medical therapy [MT]) in patients with TVD.Methods::This study was a post hoc analysis of a large, prospective cohort of patients with TVD in China, that aimed to determine the long-term outcomes after PCI, CABG, or optimal MT alone. A total of 8943 patients with TVD were consecutively enrolled between 2004 and 2011 at Fuwai Hospital. A total of 7818 patients with available baseline LAVI data were included in the study. Baseline, procedural, and follow-up data were collected. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), which was a composite of all-cause death, myocardial infarction (MI), and stroke. Secondary endpoints included all-cause death, cardiac death, MI, revascularization, and stroke. Long-term outcomes were evaluated among LAVI quartile groups. Results::During a median follow-up of 6.6 years, a higher LAVI was strongly associated with increased risk of MACCE (Q3: hazard ratio [HR] 1.20, 95% confidence interval [CI] 1.06-1.37, P = 0.005; Q4: HR 1.85, 95%CI 1.64-2.09, P <0.001), all-cause death (Q3: HR 1.41, 95% CI 1.17-1.69, P <0.001; Q4: HR 2.54, 95%CI 2.16-3.00, P <0.001), and cardiac death (Q3: HR 1.81, 95% CI 1.39-2.37, P <0.001; Q4: HR 3.47, 95%CI 2.71-4.43, P <0.001). Moreover, LAVI significantly improved discrimination and reclassification of the SYNTAX score II. Notably, there was a significant interaction between LAVI quartiles and treatment strategies for MACCE. CABG was associated with lower risk of MACCE than MT alone, regardless of LAVI quartiles. Among patients in the fourth quartile, PCI was associated with significantly increased risk of cardiac death compared with CABG (HR: 5.25, 95% CI: 1.97-14.03, P = 0.001). Conclusions::LAVI is a potential index for risk stratification and therapeutic decision-making in patients with three-vessel coronary disease. CABG is associated with improved long-term outcomes compared with MT alone, regardless of LAVI quartiles. When LAVI is severely elevated, PCI is associated with higher risk of cardiac death than CABG.

Objective:To evaluate the mid-term complication rates of the Hui-Jing one-stage procedure (lingual mucosa combined with longitudinal preputial island flap onlay urethroplasty + tubularized incised plate glansplasty)versus the classic Bracka staged surgery for children with severe hypospadias.Methods:A retrospective analysis was conducted on clinical data of 75 children with proximal hypospadias who were treated at the Seventh Medical Center of PLA General Hospital from March 2017 to June 2022. Of these patients, 31 cases (15 cases penoscrotal type and 16 cases perineal type) were underwent the Bracka two-stage surgery with a median age of 38 months (24.0, 44.5) and 44 cases underwent the Hui-Jing one-stage procedure (23 cases penoscrotal type and 21 perineal type) with a median age of 40.5 months (20.75, 90.5). The length of urethral plate defect after correction of penile curvature was (4.30±0.84)cm in the Bracka group and (4.56±0.79)cm in the Hui-Jing group, which also showed no significant difference.There was no statistically significant difference of the median age and the position of preoperative urethral opening between the two groups( P=0.47, P=0.74). The first stage of Bracka repair consists of orthoplasty and urethral bed substitution with free preputial graft. After 6 months, the urethral plate created from free graft was tabularized to form neourethra; Hui-Jing procedure group used the free lingual mucosal as urethral plate substitution, then we conducted longitudinal preputial island flap Onlay and Snodgrass phalloplasty. The incidence of postoperative urethral fistula, urethral stricture and urethral diverticulum was compared between the two groups of cases and the difference in efficacy between the two procedures was assessed. Results:Among the 75 patients included in the study, there was no statistically significant difference in age or location of urethral meatus between the Bracka and Hui-Jing groups. In Bracka group, 9 cases of urethral stricture (29.0%), 6 case of urethral fistula (19.4%), and 2 cases of urethral diverticulum (6.5%) occurred after surgery, while 12 cases of urethral fistula (27.3%) and 3 case of urethral fistula (6.8%) occurred in the Hui-Jing group. No urethral stricture occurred in Hui-Jing group. There was no statistically significant difference in overall incidence of complications between the two groups [17/31(54.8%) vs.15/44(34.1%), P=0.12]. The incidence of urethral fistula and urethral diverticulum show no significant differences between two groups(19.4% vs 27.3, P=0.61, 6.5% vs. 6.8%, P=0.13). The number of operation in Bracka group was (2.68±1.03) and the hospitalization cost was (12 984.63±3 808.15) Yuan, while the number of operation in Hui-Jing group was (1.36±0.53) and the hospitalization cost was (8 490.54±3 136.84) Yuan. Conclusions:The Hui-Jing one-stage procedure can be used for the surgical treatment of children with severe hypospadias. There is no urethral stricture happened in Hui-Jing group, while the general complication incidence and incidence of urethral fistula and diverticulum show no differences.

In this paper, the clinical data of a case of accidental poisoning of dimethylformamide in a traffic accident was analyzed. The patient was trapped in the driving room, his limbs were soaked in dimethylformamide for a long time, and dimethylformamide was inhaled at the same time. After 4 days of treatment in a local hospital, he was transferred to the Department of Poisoning & Occupational Diseases, Emergency Medicine of Qilu Hospital of Shandong University for treatment. The main clinical manifestation of the patient was liver damage and intractable abdominal pain, which was cured by active treatment.
Male ; Humans ; Dimethylformamide ; Abdominal Pain ; Occupational Diseases/complications* ; Poisoning