Mechanical pain is one of the most common causes of clinical pain, but there remains a lack of effective treatment for debilitating mechanical and chronic forms of neuropathic pain. Recently, neurotoxin GsMTx4, a selective mechanosensitive (MS) channel inhibitor, has been found to be effective, while the underlying mechanism remains elusive. Here, with multiple rodent pain models, we demonstrated that a GsMTx4-based 17-residue peptide, which we call P10581, was able to reduce mechanical hyperalgesia and neuropathic pain. The analgesic effects of P10581 can be as strong as morphine but is not toxic in animal models. The anti-hyperalgesic effect of the peptide was resistant to naloxone (an μ-opioid receptor antagonist) and showed no side effects of morphine, including tolerance, motor impairment, and conditioned place preference. Pharmacological inhibition of TRPV4 by P10581 in a heterogeneous expression system, combined with the use of Trpv4 knockout mice indicates that TRPV4 channels may act as the potential target for the analgesic effect of P10581. Our study identified a potential drug for curing mechanical pain and exposed its mechanism.

BACKGROUND:Currently,pedicle screw fixation technology is recognized as the gold standard for lumbar posterior fusion surgery.However,this technique is associated with several complications such as suboptimal screw placement,loosening,and fracture.Addressing these issues,it requires a thorough investigation into the mechanical properties of screw reinsertion to optimize surgical procedures and enhance success rates and safety.OBJECTIVE:By combining finite element analysis with biomechanical experiments,this study aims to compare and analyze the mechanical performance of traditional trajectory pedicle screws during multiple extraction processes.The goal is to reveal patterns in screw extraction strength over repeated withdrawals,providing scientific insights into the safety and effectiveness of pedicle screw reinsertion for clinicians.METHODS:Based on CT scan data,a three-dimensional reconstruction of the L4 vertebra model was performed.Three-dimensional printing technology was used to create biological experimental samples.A pull-out experiment was conducted according to a screw placement plan.Utilizing CT data and standard pedicle screw parameters,a finite element model of the L4 vertebra and a pedicle screw model(diameter 6.0 mm,length 45 mm)were established.The model was divided into five operating conditions based on screw placement angle and cycles.A finite element model was developed to simulate axial pull-out testing,analyzing stress distribution in the vertebral body and maximum axial pull-out strength of the screw.Mechanics experimental results of three-dimensional printing were compared and analyzed against simulation outcomes.RESULTS AND CONCLUSION:(1)A dedicated experimental setup for pedicle screw extraction from single vertebrae was designed and constructed.(2)In the three-dimensional printing experiment,our groups of models were compared between correctly placed screws and once improperly placed screws.The correctly placed screws group exhibited a maximum pull-out force of(1 422.63±23.80)N.Furthermore,with increasing deviation angles in screw placement,the maximum pull-out forces of each group gradually decreased.(3)Comparing the condition of a single improper nail placement with repositioning the nail correctly,when the offset angle of the improper placement exceeded that of Model 3,correctly repositioning the nail helps to increase the screw's pull-out resistance.(4)Comparing the scenario of two consecutive improper nail placements with repositioning correctly after two improper placements,correctly repositioning the nail reduced the screw's pull-out resistance.Without replacing the screw,it was not advisable to attempt a third nail placement.(5)Experimental pull-out strength of three-dimensional printing correlates significantly with finite element simulation results,with a correlation coefficient of 0.98.There is no significant difference in the outcomes between the two methods(P＞0.05).

BACKGROUND:Currently,pedicle screw fixation technology is recognized as the gold standard for lumbar posterior fusion surgery.However,this technique is associated with several complications such as suboptimal screw placement,loosening,and fracture.Addressing these issues,it requires a thorough investigation into the mechanical properties of screw reinsertion to optimize surgical procedures and enhance success rates and safety.OBJECTIVE:By combining finite element analysis with biomechanical experiments,this study aims to compare and analyze the mechanical performance of traditional trajectory pedicle screws during multiple extraction processes.The goal is to reveal patterns in screw extraction strength over repeated withdrawals,providing scientific insights into the safety and effectiveness of pedicle screw reinsertion for clinicians.METHODS:Based on CT scan data,a three-dimensional reconstruction of the L4 vertebra model was performed.Three-dimensional printing technology was used to create biological experimental samples.A pull-out experiment was conducted according to a screw placement plan.Utilizing CT data and standard pedicle screw parameters,a finite element model of the L4 vertebra and a pedicle screw model(diameter 6.0 mm,length 45 mm)were established.The model was divided into five operating conditions based on screw placement angle and cycles.A finite element model was developed to simulate axial pull-out testing,analyzing stress distribution in the vertebral body and maximum axial pull-out strength of the screw.Mechanics experimental results of three-dimensional printing were compared and analyzed against simulation outcomes.RESULTS AND CONCLUSION:(1)A dedicated experimental setup for pedicle screw extraction from single vertebrae was designed and constructed.(2)In the three-dimensional printing experiment,our groups of models were compared between correctly placed screws and once improperly placed screws.The correctly placed screws group exhibited a maximum pull-out force of(1 422.63±23.80)N.Furthermore,with increasing deviation angles in screw placement,the maximum pull-out forces of each group gradually decreased.(3)Comparing the condition of a single improper nail placement with repositioning the nail correctly,when the offset angle of the improper placement exceeded that of Model 3,correctly repositioning the nail helps to increase the screw's pull-out resistance.(4)Comparing the scenario of two consecutive improper nail placements with repositioning correctly after two improper placements,correctly repositioning the nail reduced the screw's pull-out resistance.Without replacing the screw,it was not advisable to attempt a third nail placement.(5)Experimental pull-out strength of three-dimensional printing correlates significantly with finite element simulation results,with a correlation coefficient of 0.98.There is no significant difference in the outcomes between the two methods(P＞0.05).

Objective: To prospectively compare single-shot (SS) echo-planar imaging (EPI) and field-of-view optimized and constrained undistorted single-shot multiplexed sensitivity-encoding (FOCUS MUSE) for diffusion-weighted imaging (DWI) in evaluating thyroid-associated ophthalmopathy (TAO). Materials and Methods: SS EPI and FOCUS MUSE DWIs were obtained from 39 patients with TAO (18 male; mean ± standard deviation: 48.3 ± 13.3 years) and 26 healthy controls (9 male; mean ± standard deviation: 43.0 ± 18.5 years). Two radiologists scored the visual image quality using a 4-point Likert scale. The image quality score, signal-to-noise ratio (SNR), contrast-tonoise ratio (CNR), and apparent diffusion coefficient (ADC) of extraocular muscles (EOMs) were compared between the two DWIs. Differences in the ADC of EOMs were also evaluated. The performance of discriminating active from inactive TAO was assessed using receiver operating characteristic curves. The correlation between ADC and clinical activity score (CAS) was analyzed using Spearman correlation. Results: Compared with SS EPI DWI, FOCUS MUSE DWI demonstrated significantly higher image quality scores (P < 0.001), a higher SNR and CNR on the lateral rectus muscle (LRM) and medial rectus muscle (MRM) (P < 0.05), and a non-significant difference in the ADC of the LRM and MRM. Active TAO showed higher ADC than inactive TAO and healthy controls with both SS EPI and FOCUS MUSE DWIs (P < 0.001). Inactive TAO and healthy controls did not show a significant ADC difference with both DWIs. Compared with SS EPI DWI, FOCUS MUSE DWI demonstrated better discrimination of active from inactive TAO (AUC:0.925 vs. 0.779; P = 0.007). The ADC was significantly correlated with CAS in SS EPI DWI (r = 0.391, P < 0.001) and FOCUS MUSE DWI (r = 0.645, P < 0.001). Conclusion FOCUS MUSE DWI provides better images for evaluating EOMs and better performance in diagnosing active TAO than SS EPI DWI. The application of FOCUS MUSE will facilitate the DWI evaluation of TAO.

Objective To explore the impact of Suzi Jiangqi decoction(SJD)on the inflammatory state of patients with chronic obstructive pulmonary disease(COPD)through the regulation of the mitogen-activated protein kinase(MAPK)signaling pathway.Methods A total of 70 patients with stable COPD,treated from April 2023 to April 2024 at the Department of Traditional Chinese Medicine and Department of Respiratory outpatient clinic of Affiliated Jinhua Hospital,School of Medicine Zhejiang University were selected and randomly divided into observation group and control group,with 35 cases in each group.The control group received tiotropium bromide powder inhalation combined with budesonide/formoterol powder inhalation treatment,while the observation group was given SJD in addition to treatment of control group.After 12 weeks of treatment,the therapeutic effects were evaluated by assessing lung function,airway mucus hypersecretion,levels of interleukin(IL)-17,IL-6,and tumor necrosis factor(TNF)-α,CT quantitative parameters of the lung,as well as the expression levels of IL-17,p38MAPK,nuclear factor kappa-B(NF-κB)and C-X-C motif chemokine ligand 8(CXCL8)mRNA in sputum.Results Following treatment,there was a significant improvement in lung function indicators such as first second expiratory volume/forced vital capacity％,cough score,sputum difficulty score,sputum quality score,and sputum volume score for patients in both groups,with more pronounced improvements observed in observation group(P＜0.05).The levels of serum cytokines IL-17,IL-6 and TNF-αdecreased in both groups after treatment,with observation group showing a more significant reduction(P＜0.05).Additionally,the percentage ratio of low attenuation area to lung area(LAA％),emphysema index of lung CT in observation group significantly decreased after treatment(P＜0.05).Similarly,the expression levels of IL-17,p38MAPK,NF-κB and CXCL8 mRNA in sputum were also significantly reduced after treatment in observation group(P＜0.05).Conclusion SJD may improve lung function and inflammatory status in COPD patients by regulating the MAPK signaling pathway mediated by IL-17,demonstrating a positive therapeutic effect on the treatment of COPD.

Neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision (TME) and adjuvant chemotherapy serves as a traditional standard treatment for locally advanced rectal cancer (LARC). However, such treatment suffers low pathological complete response (pCR) rates, which are merely less than 15%, and low anal-preservation rates, failing to meet the demand of patients for high quality of life. Recently, total neoadjuvant therapy (TNT) whereby postoperative adjuvant chemotherapy is performed preoperatively has further increased the pCR rate, gradually becoming a novel therapeutic approach. Nevertheless, the pCR rate of TNT remains below 30%. Presently, immune checkpoint inhibitors (ICIs) have been proved to be highly successful in treating various solid tumors, yet they are scarcely employed to treat LARC. In recent years, many clinical trials have been conducted to explore the application of nCRT combined with ICIs in the treatment of LARC. This paper reviews the advances in research on this therapy.

Objective:To investigate the status quo of psychological contracts and influencing factors among members of the "1+N" family doctor teams in Shenzhen and to explore the impact of psychological contracts on job burnout.Methods:This cross-sectional study was conducted from September 30 to October 31, 2022 among 361 members of 92 family doctor teams from 92 community health service centers which provided family doctor team service in Shenzhen city. A self-designed general information questionnaire, an employee psychological contract questionnaire (including organizational responsibility and personal responsibility dimensions), and a job burnout scale (including emotional exhaustion, depersonalization, and personal accomplishment dimensions) were used in the study. T-tests, one-way ANOVA, Pearson correlation analysis, and multiple linear regression analysis were used to analyze the influencing factors of psychological contracts and job burnout.Results:Among 361 respondents, there were 299 females (82.8%) and 62 males (17.2%), and a higher proportion of general practitioners (37.5%, 129/361) and nurses (41.8%, 151/361). The total score of psychological contracts among the 361 respondents was (141.6±19.5), with organizational responsibility scoring (70.6±11.2) and personal responsibility scoring (71.0±9.3). On the job burnout scale, emotional exhaustion scored (17.89±6.82), depersonalization scored (6.51±2.54), and personal accomplishment scored (30.95±5.70). General practitioners scored lower in organizational responsibility and personal responsibility compared to other members ( F=7.341,3.119, all P<0.05), and higher in emotional exhaustion and depersonalization ( F=7.637, 2.415, all P<0.05). Members with≤5 years of work experience scored lower in personal responsibility and personal accomplishment ( F=3.656, 4.205, all P<0.05). Correlation analysis showed that scores of organizational responsibility and personal responsibility were negatively correlated with levels of emotional exhaustion and depersonalization ( r=-0.618, -0.526, all P<0.01), ( r=-0.404, -0.393, all P<0.01), and positively correlated with personal accomplishment ( r=0.500, 0.558, all P<0.01). Multiple linear regression analysis indicated that organizational responsibility negatively affected emotional exhaustion and depersonalization ( β=-0.554, -0.274, all P<0.01), and positively affected personal accomplishment ( β=0.172, P<0.05). Personal responsibility positively affected personal accomplishment ( β=0.404, P<0.01). Conclusions:The study demonstrates that general practitioners in family doctor teams in Shenzhen city have lower psychological contract levels and are more prone to emotional exhaustion and depersonalization; members with≤5 years of work experience have lower personal responsibility and accomplishment. The results indicate that enhancing organizational responsibility can reduce job burnout of members in family doctor teams.

Objective To investigate the effect of colquhounia root tablet(CRT)on hyperglucose-in-duced epithelial-mesenchymal transition(EMT)in renal tubular epithelial cells(HK-2),and to explore its possible action mechanism.Methods HK-2 was cultured in vitro,and HK-2 was divided into the following five groups:control group(CON group),hyperosmolar group(MA group),high glucose group(HG group),high sugar+CRT group(HG+CRT group),high sugar+phosphatidylinositol 3 kinase inhibitor group(HG+LY29400 group),high sugar+CRT+phosphatidylinositol 3 kinase inhibitor group(HG+CRT+LY29400).The real time immunofluorescence quantitative PCR(qPCR)was used to detect the mRNA ex-pression levels of E-cadherin,α-smooth muscle actin(α-SMA)and phosphatase and tensin homolog(PTEN)in each group.Western-blot was used to detect the protein expression levels of PTEN,phosphatidylinositol 3 kinase(PI3K),protein kinase B(Akt),phosphorylated protein kinase B(p-Akt),E-cadherin and α-SMA in each group.Results Compared with the CON group,the protein and mRNA expression levels of α-SMA,p-Akt protein expression level and p-Akt/Akt ratio in the HG group were increased,the protein and mRNA ex-pression levels of E-cadherin and PTEN were decreased,and the differences were statistically significant(P＜0.05).Compared with the HG group,the α-SMA protein and mRNA expression levels in the HG+CRT group were decreased,while the E-cadherin protein and mRNA expression levels were increased,and the differences were statistically significant(P＜0.05).Compared with the HG+CRT group,there was no significant differ-ence in the E cadherin,α SMA,PTEN,P13K and Akt protein expression levels and p-Akt/Akt ratio in the HG+CRT+LY29400 group had no significant differences(P＞0.05).while the expression level of p-Akt protein was increased,and the difference was statistically significant(P＜0.05).Conclusion In vitro,CRT could re-verse hyperglucose-induced renal tubular epithelial cell EMT via the PTEN/PI3K/Akt signaling pathway.

Objective:To explore the role and mechanism of tubastatin A (TubA) in alleviating brain injury after cardiac arrest and cardiopulmonary resuscitation (CA-CPR) by inhibiting endoplasmic reticulum stress-mediated cell apoptosis in swine.Methods:Twenty-three conventional male white swine, weighing 33-40 kg, aged 4 to 6 months, were divided into 3 groups by random number table method: sham group ( n=6), CA-CPR group ( n=9), and TubA group ( n=8). The CA-CPR swine model was established by 9 min of electrically induced CA through pacing catheter in the right ventricle and then 6 min of CPR in the CA-CPR group. The CA-CPR swine model was established by the same method, and then a dose of 4.5 mg/kg of TubA at 5 min after resuscitation was intravenously infused in the TubA group. The serum concentrations of neuron specific enolase (NSE) and S100β protein (S100β) were measured using ELISA before modeling and at 1, 2, 4 and 24 h after resuscitation. Neurological deficit score (NDS) was evaluated at 24 h after resuscitation. Thereafter, the animals were euthanized, and brain cortex tissues were harvested, and the expression levels of caspase-12 and caspase-3 were measured using immunohistochemistry. Cell apoptosis index was detected by TUNEL assay. The variables among the three groups were compared with one-way analysis of variance and the Bonferroni hoc test using SPSS software. Results:Twenty-four h after resuscitation, the serum concentrations of NSE and S100β were significantly increased, and NDS was markedly elevated in the CA-CPR and TubA groups compared with the sham group (all P<0.05). Compared with the CA-CPR group, serum concentration of NSE starting 2 h after resuscitation and serum concentration of S100β starting 1 h after resuscitation were significantly decreased in the TubA group [NSE (ng/mL): (23.1±2.0) vs. (20.2±2.0) at 2 h, (28.4±2.3) vs. (23.7±1.9) at 4 h, (32.1±2.7) vs. (26.6±2.0) at 24 h; S100β (pg/mL): (2239±193) vs. (1923±101) at 1 h, (2817±157) vs. (2360±141) at 2 h, (3384±250) vs. (2691±210) at 4 h, (3965±303) vs. (3119±260) at 24 h, all P<0.05], and NDS was markedly reduced (240±30 vs. 63±44, P<0.05). At 24 h after resuscitation, brain cortex tissue detection showed that the expression levels of caspase-12 and caspase-3 were significantly increased, and cell apoptosis index was markedly elevated in the CA-CPR and TubA groups compared with the sham group (all P<0.05). However, the expression levels of caspase-12 and caspase-3 were significantly decreased [caspase-12:(7.1±0.7) vs. (4.2±0.4); caspase-3: (13.3±1.6) vs. (7.7±0.8), all P<0.05], and cell apoptosis index was markedly reduced in the TubA group compared to the CA-CPR group [(31.1±8.6) vs. (17.3±2.2), P<0.05]. Conclusions:TubA alleviates brain injury and neurological dysfunction after CA-CPR in swine, which may be related to the inhibition of cell apoptosis mediated by endoplasmic reticulum stress.

Objective:To investigate the effects of Satir model group intervention on stress coping style, self-consistency and congruence and subjective well-being of re-employment nurses, in order to provide evidence for nursing managers to take targeted intervention measures.Methods:This was a quasi-experimental study. Convenience sampling was used to select 63 re-employment nurses from Shandong Provincial Third Hospital in 2021 as the research objects. The re-employment nurses were divided into control group (32 cases) and observation group (31 cases) by random number table method. The control group received humanistic care including heart-to-heart talk, group discussion and psychological lecture, and the observation group received Satir model group intervention for 6 weeks. Simplified Coping Style Questionnaire, Self Consistency and Congruence Scale and General Well-Being Scale were used to evaluate the intervention effect before intervention, immediately after intervention, 3 months after intervention, and 6 months after intervention.Results:There was no significant difference in coping style, self-consistency and congruence and subjective well-being between the two groups before intervention ( P>0.05). The positive coping scores of the observation group immediately after intervention, 3 months after intervention and 6 months after intervention were (28.94 ± 2.99), (28.71 ± 4.70) and (29.16 ± 3.23) points, significantly higher than the control group (23.38 ± 5.50), (24.72 ± 5.91), (24.65 ± 5.65) points, the differences were statistically significant ( t=4.96, 2.96, 3.87, all P<0.01); the total self-consistency and congruence scores were (94.52 ± 14.00), (99.87 ± 16.82), (91.84 ± 10.36) points, significantly lower than the control group (105.72 ± 10.75), (114.23 ± 20.10), (107.41 ± 13.39) points, the differences were statistically significant ( t=-3.57, -3.07, -5.15, all P<0.01); the total subjective well-being scores were (84.97 ± 7.37), (84.58 ± 10.33), (91.84 ± 7.01) points, which were higher than the control group (75.69 ± 7.94), (77.28 ± 8.27), (77.00 ± 8.48) points, and the differences were statistically significant ( t=4.80, 3.69, 7.56, all P<0.01). Conclusions:Satir model group intervention can improve the coping style, enhance the level of self-consistency and congruence and subjective well-being among re-employment nurses.