BACKGROUND:The use of 3D-printed patient-specific instruments in opening wedge high tibial osteotomy has advantages such as shorter operative time,fewer fluoroscopic exposures,and higher correction accuracy.However,previous studies have reported issues such as significant damage to surrounding soft tissues and improper fixation of the plates. OBJECTIVE:To investigate the clinical efficacy of using 3D-printed patient-specific instruments combined with customized locking plate in opening wedge high tibial osteotomy for the treatment of knee osteoarthritis. METHODS:A total of 20 patients diagnosed with knee osteoarthritis were divided into the 3D group(n=10)and the conventional group(n=10)according to surgical methods.The 3D group underwent opening wedge high tibial osteotomy using 3D-printed patient-specific instruments combined with customized locking plate,while the conventional group underwent opening wedge high tibial osteotomy using conventional methods.The operative time,fluoroscopic exposures,incision length,pre-and postoperative hip-knee-ankle angle,medial proximal tibial angle,posterior tibial slope,the difference between the planned and actual correction angle,preoperative and 1,3,6 months postoperative knee range of motion and Lysholm score,and incidence of complications were analyzed and compared between the two groups. RESULTS AND CONCLUSION:(1)The operative time and fluoroscopic exposures were significantly shorter in the 3D group compared to the conventional group,with a statistically significant difference(P<0.001).(2)Both groups showed a significant improvement in postoperative hip-knee-ankle angle and medial proximal tibial angle compared to preoperative values,with a statistically significant difference(P<0.001),while there was no significant change in posterior tibial slope.In the 3D group,the postoperative hip-knee-ankle angle,medial proximal tibial angle,and posterior tibial slope differed from their respective preoperative planned values by(-0.22±0.72)°,(-0.20±0.73)°,and(0.23±0.37)°,but the differences were not statistically significant.The difference between the planned and actual correction angle of 3D group was significantly smaller than that of conventional group(P<0.05).(3)Both groups showed a gradual increase in knee range of motion and Lysholm scores after surgery(P<0.001).Compared to the conventional group,the 3D group had superior knee range of motion at 1 and 3 months postoperatively,as well as a higher Lysholm score at 1 month postoperatively,with statistically significant differences(P<0.05).There were no statistically significant differences in Lysholm score at 3 months and knee range of motion and Lysholm score at 6 months between the two groups(P>0.05).(4)Complications occurred in neither groups.(5)The above results indicate that both 3D-printed patient-specific instruments combined with customized locking plate and conventional methods have good clinical efficacy.However,the former has a shorter operative time,fewer fluoroscopic exposures,and faster postoperative recovery of knee joint function.Additionally,3D-printed patient-specific instruments can achieve preoperative planning accurately.

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopamine (DA) neurons in the substantia nigra pars compacta (SNpc), primarily manifesting as motor dysfunctions such as resting tremor, muscle rigidity, and bradykinesia. According to the classical model of basal ganglia motor control, approximately half of the medium spiny neurons (MSNs) in the striatum are D1-MSNs, which constitute the direct pathway. These neurons express D₁-dopamine receptor (D₁R) and substance P, and they mainly participate in the selection, initiation, and execution of movements. The other half are D2-MSNs, which constitute the indirect pathway. These neurons express D₂-dopamine receptor (D₂R) and adenosine 2A receptors and are involved in inhibiting unnecessary movements or terminating ongoing movements, thereby adjusting movement sequences to perform more precise motor behaviors. The direct pathway in the striatum modulates the activity of motor cortex neurons by exciting D1-MSNs through neurotransmitters such as glutamate (Glu), allowing the motor cortex to send signals more freely to the motor system, thus facilitating the generation and execution of specific motor behaviors. Studies using D1-Cre and D2-Cre mice with neurons labeled for D₁R and D₂R have shown that both types of neurons are involved in the execution of movements, with D1-MSNs participating in movement initiation and D2-MSNs in inhibiting actions unrelated to the target movement. These findings suggest that the structural and functional plasticity of D1-MSNs and D2-MSNs in the basal ganglia circuitry enables motor learning and behavioral regulation. Additionally, when SNpc DA neurons begin to degenerate, D1-MSNs are initially affected but do not immediately cause motor impairments. In contrast, when D2-MSNs undergo pathological changes, they are first activated by upstream projecting neurons, leading to the inhibition of most motor behaviors and resulting in motor dysfunction. Therefore, it is hypothesized that motor impairments such as bradykinesia and initiation difficulties are more closely related to the functional activity of D2-MSNs. The extracellular signal-regulated kinase (Erk)/mitogen-activated protein kinase (MAPK) signaling pathway has been identified as a critical modulator in the pathophysiology of PD. Recent findings indicate that Erk/MAPK signaling pathway can mediate DA and Glu signaling in the central nervous system, maintaining normal functional activity of striatal MSNs and influencing the transmission of motor control signals. Within this complex regulatory network, the Erk/MAPK signaling pathway plays a key role in transmitting motor information to downstream neurons, regulating normal movements, avoiding unnecessary movements, and finely tuning motor behaviors. Our laboratory’s previous research found that 4 weeks of aerobic exercise intervention improved motor dysfunction in PD mice by inhibiting the Erk1/2 signaling upstream of striatal MSNs, primarily involving the Erk1/2 signaling in D2-MSNs rather than D1-MSNs. This review summarizes the neurobiological mechanisms of Erk/MAPK signaling pathway in D2-MSNs for the prevention and treatment of motor dysfunction in PD. By exploring the role of this signaling pathway in regulating motor abnormalities and preventing motor dysfunction in the central nervous system of PD, this review provides new theoretical perspectives for related mechanistic research and therapeutic strategies.

Objective To study the effect of auditory and speech development after cochlear implant(CI)in children with bilateral cochlear nerve deficiency(CND)and its influencing factors.Methods A total of 20 children with bilateral CND were included in the study,of which 5 were implanted bilaterally and 15 unilaterally.CT of the temporal bone showed stenosis of the cochlear aperture in 14 cases and atresia of the cochlear aperture in 6 cases.There were 8 cases accompanied by other inner ear malformations,and 12 cases with no accompanying inner ear mal-formations.MRI of the internal auditory canal showed 1 nerve in 5 cases,2 nerves in 6 cases,3 nerves in 8 cases,and 4 nerves in 1 case.There were 6 cases in which the EABR was not elicited and 14 cases in which it was elicited.The postoperative auditory and speech abilities of the subjects were evaluated using categories of auditory perform-ance(CAP)and speech intelligibility rating(SIR).Results ① The CAP(P＜0.001)and SIR(P＜0.001)scores of the children with stenosis of the cochlea nerve canal were higher than those of the patients with atresia of the cochlea nerve canal.② The more nerve roots in the internal auditory canal,the higher the score of CAP(P=0.003)and SIR(P=0.008).③ CAP score of the children with EABR elicited was higher than that of the children without EABR elicited(P=0.030).The difference in SIR scores was not statistically significant(P=0.14).④The differences in CAP and SIR between those with bilateral CI and unilateral CI,as well as between those with and without other inner ear malformations,were not statistically significant(P＞0.05).Conclusion Children with bi-lateral CND had significant postoperative improvement in auditory function but poor speech development after CI.Postoperative auditory speech ability was related to the condition of the cochlear foramen,the number of nerve roots in the internal auditory canal,and whether or not the EABR was elicited intraoperatively.

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 investigate the association of skeletal muscle function(including muscle strength and physical performance) and insulin resistance as well as type 2 diabetes mellitus(T2DM).Methods:The retrospective study included 942 patients who visited the Department of Geriatrics at Renji Hospital, Shanghai Jiao Tong University School of Medicine, between October 2020 and July 2024. Low skeletal muscle function was defined as either reduced muscle strength or impaired physical performance. Muscle strength was assessed by grip strength, while physical performance was evaluated using the 5-time chair stand test. The associations between muscle function, insulin resistance, and T2DM were analyzed.Results:A significant association was observed between decreased skeletal muscle function and a higher prevalence of T2DM( P=0.001). Further analysis revealed that decreased physical performance was significantly associated with increased T2DM prevalence( P<0.001), whereas reduced muscle strength showed no significant association with T2DM prevalence( P=0.331). Linear regression analysis indicated that both the homeostasis model assessment of insulin resistance(HOMA2-IR) and fasting blood glucose levels increased significantly with longer chair stand times( P<0.05). Restrictive cubic spline(RCS) analysis demonstrated a nonlinear relationship between chair-rising time and HOMA2-IR. Notably, when the cumulative chair-rising time exceed 8.1 s, HOMA2-IR increased significantly with prolonged chair stand time. Logistic regression analysis showed that compared with patients with normal physical performance, those with decreased physical performance had significantly higher odds of T2DM( OR=2.64, P<0.001) and insulin resistance( OR=2.34, P=0.002). Conclusion:Decline in physical performance is significantly positively associated with insulin resistance and the risk of T2DM. Morever, when the cumulative chair stand time exceed 8.1 s, HOMA2-IR increases progressively with further prolongation of chair stand time.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

Objective:To investigate the association of skeletal muscle function(including muscle strength and physical performance) and insulin resistance as well as type 2 diabetes mellitus(T2DM).Methods:The retrospective study included 942 patients who visited the Department of Geriatrics at Renji Hospital, Shanghai Jiao Tong University School of Medicine, between October 2020 and July 2024. Low skeletal muscle function was defined as either reduced muscle strength or impaired physical performance. Muscle strength was assessed by grip strength, while physical performance was evaluated using the 5-time chair stand test. The associations between muscle function, insulin resistance, and T2DM were analyzed.Results:A significant association was observed between decreased skeletal muscle function and a higher prevalence of T2DM( P=0.001). Further analysis revealed that decreased physical performance was significantly associated with increased T2DM prevalence( P<0.001), whereas reduced muscle strength showed no significant association with T2DM prevalence( P=0.331). Linear regression analysis indicated that both the homeostasis model assessment of insulin resistance(HOMA2-IR) and fasting blood glucose levels increased significantly with longer chair stand times( P<0.05). Restrictive cubic spline(RCS) analysis demonstrated a nonlinear relationship between chair-rising time and HOMA2-IR. Notably, when the cumulative chair-rising time exceed 8.1 s, HOMA2-IR increased significantly with prolonged chair stand time. Logistic regression analysis showed that compared with patients with normal physical performance, those with decreased physical performance had significantly higher odds of T2DM( OR=2.64, P<0.001) and insulin resistance( OR=2.34, P=0.002). Conclusion:Decline in physical performance is significantly positively associated with insulin resistance and the risk of T2DM. Morever, when the cumulative chair stand time exceed 8.1 s, HOMA2-IR increases progressively with further prolongation of chair stand time.

This study aims to simultaneously detect three antibiotic resistance genes(blaNDM,mcr-1 and cfr).A triplex fluorescence quantitative PCR method was established.Plasmids,primers and probes were designed and optimized.The method could specifically detect blaNDM,mcr-1 and cfr,but not other antibiotic resistance genes.The R2 of the standard curves of the three antibiotic re-sistance genes were all greater than 0.999,and the coefficients of variation were all lower than 1％.The lowest detection limits of the plasmids were 1 × 102 copies/μL.This method was used to de-tect 800 bacterial samples.The results showed that 32 samples contained mcr-1 gene,40 samples contained blaNDM gene,2 samples contained cfr gene,8 samples contained both mcr-1 and blaNDM genes.There were no samples carrying three antibiotic resistance genes detected.The results indica-ted that the triplex fluorescence quantitative PCR method established in this experiment had the advantages of high sensitivity,specificity and stability.It was suitable for rapid detection of blaNDM,mcr-1 and cfr antibiotic resistance genes in clinical practice.It provided a convenient and quick method basis for the detection of antibiotic resistance genes.

The active ingredient of WINREVAIR,sotatercept-csrk,is a recombinant activin receptor ⅡA-Fc(ActRⅡA-Fc)fusion protein that improves pro-proliferation(ActRⅡA/Smad2/3-mediated)and anti-proliferation(BMPRⅡ/Smad 1/5/8-mediated)signals,thereby regulating vascular proliferation.In March 2024,WINREVAIR was approved by the U.S.Food and Drug Administration for the treatment of pulmonary arterial hypertension(PAH)in adults.Clinical studies have shown that WINREVAIR can improve exercise capacity and reduce the incidence of all-cause death or clinical worsening of PAH by 84％.Common adverse drugreactions include headache,epistaxis,rash,etc.