ObjectiveTo investigate the effect of Tougu Xiaotong capsules （TGXTC） on the regulation of chondrocyte PANoptosis， delay of chondrocyte degeneration， and improvement of the symptoms in knee osteoarthritis （KOA）. MethodsIn vivo experiments： 50 male C57BL/6 mice were randomly assigned into five groups （n=10 per group）： sham operation group， model group， low-dose TGXTC group （7.2 g·kg^-1）， high-dose TGXTC group （14.4 g·kg^-1）， and diclofenac sodium group （0.05 g·kg^-1）. Except for the sham group， KOA models were established in all other groups using the modified Hulth method. Following successful model induction， the TGXTC groups received daily oral gavage of 7.2 or 14.4 g·kg^-1 for 6 weeks， while the diclofenac sodium group received 0.05 g·kg^-1 solution daily over the same duration. Model evaluation was performed using Lequesne MG score； micro-computed tomography （micro-CT） was used to scan the knee， hematoxylin-eosin （HE） staining and safranin O-fast green staining were used to observe the morphology of cartilage， transmission electron microscopy （TEM） was used to determine ultrastructural changes of PANoptosis. Multiple immunofluorescence （IF） co-localization assays was performed to detect the co-localization of cleaved Caspase-3， receptor-interacting protein 3 （RlPK3）， and the N-terminal domain of gasdermin D （GSDMD-N） in cartilage tissue， while western blot was employed to detect the expression levels of cleaved Caspase-3， RIPK3， and GSDMD-N. In vitro experiments： The knee cartilages of 4-week-old SD rats were isolated， and a chondrocyte in vitro culture system was established through mechanical digestion with 0.2% type Ⅱ collagenase. Second-generation chondrocytes were divided into three groups： the control group， the model group （pretreated with 10 mg·L^-1 lipopolysaccharide （LPS） for 24 h followed by treatment with 1 μmol·L^-1 nigericin for 4 h）， and the TGXTC treatment group （pretreated with 10 mg·L^-1 LPS for 24 h， followed by exposure to 1 μmol·L^-1 nigericin for 4 h and subsequently treated with 100 mg·L^-1 TGXTC for an additional 24 h）. The levels of reactive oxygen species （ROS）， apoptosis， necroptosis， and pyroptosis of chondrocytes were evaluated via fluorescence microscopy following staining with ROS detection， AO/EB and YO-PRO-1/PI staining kits. Transmission electron microscopy was utilized to investigate the ultrastructural changes associated with PANoptosis in cartilage tissue of KOA mice. Inflammatory cytokine levels （IL-1β and IL-18） were measured using ELISA. Western blot was conducted to assess protein expressions related to PANoptosis， including cleaved Caspase-3， cleaved Caspase-8， RIPK3， ZBP1， GSDMD-N， and NLRP3. ResultsCompared with the sham group， the Lequesne MG scores were significantly up-regulated（P<0.01） in the model group， and the pathological changes of cartilage were significantly， with joint spaces narrower， osteophyte formation increased， secere abrasion of cartilage surface. Ultrastructural analysis revealed pronounced chondrocyte apoptosis， necroptosis， and pyroptosis， along with markedly elevated expression of cleaved Caspase-3， RlPK3， and GSDMD-N in cartilage tissue （P<0.01）. In addition， The mean fluorescence intensities of ROS， orange-red fluorescence in AO/EB staining， green fluorescence and red fluorescence in YO-PRO-1/PI staining were increased of chondrocyte in the model group （P<0.01） . The levels of inflammatory factors IL-1β and IL-18 in the supernatant were increased （P<0.01）. The expression of PANoptosis related proteins （cleaved Caspase-3， cleaved Caspase-8， RIPK3， ZBP1， GSDMD-N， and NLRP3） were also significantly upregulated（P<0.05）. Compared to the model group， the TGXTC group demonstrated a significant improvement in various parameters of mice. These included a reduction in the Lequesne MG score， an increase in joint space， a decrease in osteophyte formation， diminished cartilage damage， reduced release of ROS， and alleviation of apoptotic， necroptotic， and pyroptotic processes in chondrocytes. Additionally， mitochondrial swelling and endoplasmic reticulum dilation were also mitigated. The levels of ROS as well as IL-1β and IL-18 were significantly decreased （P<0.05）. Furthermore， the expression levels of proteins associated with PANoptosis in cartilage tissue showed marked reductions （P<0.05）. Similar results were observed in chondrocytes： cleaved Caspase-3， cleaved Caspase-8， RIPK3， ZBP1， GSDMD-N， and NLRP3 exhibited significant decreases as well （P<0.05）. ConclusionTGXTC may mitigate chondrocytes degeneration and alleviate KOA symptoms by reducing oxidative stress and suppressing the activation of PANoptosis pathways.

ObjectiveTo investigate the effect of Tougu Xiaotong capsules （TGXTC） on the regulation of chondrocyte PANoptosis， delay of chondrocyte degeneration， and improvement of the symptoms in knee osteoarthritis （KOA）. MethodsIn vivo experiments： 50 male C57BL/6 mice were randomly assigned into five groups （n=10 per group）： sham operation group， model group， low-dose TGXTC group （7.2 g·kg^-1）， high-dose TGXTC group （14.4 g·kg^-1）， and diclofenac sodium group （0.05 g·kg^-1）. Except for the sham group， KOA models were established in all other groups using the modified Hulth method. Following successful model induction， the TGXTC groups received daily oral gavage of 7.2 or 14.4 g·kg^-1 for 6 weeks， while the diclofenac sodium group received 0.05 g·kg^-1 solution daily over the same duration. Model evaluation was performed using Lequesne MG score； micro-computed tomography （micro-CT） was used to scan the knee， hematoxylin-eosin （HE） staining and safranin O-fast green staining were used to observe the morphology of cartilage， transmission electron microscopy （TEM） was used to determine ultrastructural changes of PANoptosis. Multiple immunofluorescence （IF） co-localization assays was performed to detect the co-localization of cleaved Caspase-3， receptor-interacting protein 3 （RlPK3）， and the N-terminal domain of gasdermin D （GSDMD-N） in cartilage tissue， while western blot was employed to detect the expression levels of cleaved Caspase-3， RIPK3， and GSDMD-N. In vitro experiments： The knee cartilages of 4-week-old SD rats were isolated， and a chondrocyte in vitro culture system was established through mechanical digestion with 0.2% type Ⅱ collagenase. Second-generation chondrocytes were divided into three groups： the control group， the model group （pretreated with 10 mg·L^-1 lipopolysaccharide （LPS） for 24 h followed by treatment with 1 μmol·L^-1 nigericin for 4 h）， and the TGXTC treatment group （pretreated with 10 mg·L^-1 LPS for 24 h， followed by exposure to 1 μmol·L^-1 nigericin for 4 h and subsequently treated with 100 mg·L^-1 TGXTC for an additional 24 h）. The levels of reactive oxygen species （ROS）， apoptosis， necroptosis， and pyroptosis of chondrocytes were evaluated via fluorescence microscopy following staining with ROS detection， AO/EB and YO-PRO-1/PI staining kits. Transmission electron microscopy was utilized to investigate the ultrastructural changes associated with PANoptosis in cartilage tissue of KOA mice. Inflammatory cytokine levels （IL-1β and IL-18） were measured using ELISA. Western blot was conducted to assess protein expressions related to PANoptosis， including cleaved Caspase-3， cleaved Caspase-8， RIPK3， ZBP1， GSDMD-N， and NLRP3. ResultsCompared with the sham group， the Lequesne MG scores were significantly up-regulated（P<0.01） in the model group， and the pathological changes of cartilage were significantly， with joint spaces narrower， osteophyte formation increased， secere abrasion of cartilage surface. Ultrastructural analysis revealed pronounced chondrocyte apoptosis， necroptosis， and pyroptosis， along with markedly elevated expression of cleaved Caspase-3， RlPK3， and GSDMD-N in cartilage tissue （P<0.01）. In addition， The mean fluorescence intensities of ROS， orange-red fluorescence in AO/EB staining， green fluorescence and red fluorescence in YO-PRO-1/PI staining were increased of chondrocyte in the model group （P<0.01） . The levels of inflammatory factors IL-1β and IL-18 in the supernatant were increased （P<0.01）. The expression of PANoptosis related proteins （cleaved Caspase-3， cleaved Caspase-8， RIPK3， ZBP1， GSDMD-N， and NLRP3） were also significantly upregulated（P<0.05）. Compared to the model group， the TGXTC group demonstrated a significant improvement in various parameters of mice. These included a reduction in the Lequesne MG score， an increase in joint space， a decrease in osteophyte formation， diminished cartilage damage， reduced release of ROS， and alleviation of apoptotic， necroptotic， and pyroptotic processes in chondrocytes. Additionally， mitochondrial swelling and endoplasmic reticulum dilation were also mitigated. The levels of ROS as well as IL-1β and IL-18 were significantly decreased （P<0.05）. Furthermore， the expression levels of proteins associated with PANoptosis in cartilage tissue showed marked reductions （P<0.05）. Similar results were observed in chondrocytes： cleaved Caspase-3， cleaved Caspase-8， RIPK3， ZBP1， GSDMD-N， and NLRP3 exhibited significant decreases as well （P<0.05）. ConclusionTGXTC may mitigate chondrocytes degeneration and alleviate KOA symptoms by reducing oxidative stress and suppressing the activation of PANoptosis pathways.

Objective:To describe the safety of using the Chinese-made robotic laparoscopic surgery system for laparoscopic sacrocolpopexy in the treatment of severe pelvic organ prolapse.Methods:A pilot descriptive clinical study was conducted, enrolling 16 severe pelvic organ prolapse patients at Peking University First Hospital from April 2023 to January 2024. Patients who consented to participate in this study underwent laparoscopic sacrocolpopexy for severe pelvic organ prolapse using Chinese-made robotic laparoscopic surgery system. Preoperative clinical basic data and perioperative data of the patients were collected, summarizing the data on perioperative bleeding and complications, and reviewed the surgical learning experience. The evaluation indicators related to the learning experience included: (1) efficiency evaluation: including equipment docking time, total surgery time, suturing time, mechanical arm operation time and hysterectomy time, which were timed and recorded during surgery; (2) equipment operability evaluation: including equipment operation task load assessment and intraoperative operation feeling score. The cumulative sum analysis method was used to quantify surgery time and fit the learning curve.Results:Sixteen patients were successfully enrolled and underwent surgery, including total hysterectomy with bilateral salpingo-oophorectomy or salpingectomy plus sacrocolpopexy, or sacrocolpopexy alone (for one case without uterus). The age of 16 cases was (56.7±7.6) years (ranged from 44 to 67 years), with body mass index of (25.4±2.5) kg/m2. Concurrent procedures included anterior vaginal wall repair in 12 cases (12/16), posterior vaginal wall repair in 13 cases (13/16), tension-free vaginal tape obturator system in 1 case (1/16), and recto-uterine pouch hernia repair in 4 cases (4/16). The total surgery time was (355.8±91.1) minutes, with docking time at (6.7±4.9) minutes, robotic operative time at (267.6±81.4) minutes, robotic suturing time at (155.6±53.9) minutes, and hysterectomy time at (112.0±45.3) minutes. Learning curve analysis revealed inflection points at 6 cases for total surgery time ( P<0.001, R2=0.944) and robotic operative time ( P<0.001, R2=0.982), 5 cases for docking time ( P<0.001, R2=0.989), and 6 cases for robotic suturing time ( P<0.001, R2=0.907). Hysterectomy time had an inflection point at 5 cases ( P=0.023, R2=0.700). Median blood loss was 30 ml (range: 10-1 000 ml), with severe bleeding in one patient (1/16). No conversions to open surgery or laparoscopy occurred, and no severe perioperative or postoperative complications were reported. Conclusion:The Chinese-made robotic laparoscopic surgery system demonstrates excellent short-time safety and ease of operation for laparoscopic sacrocolpopexy.

BACKGROUND:Our previous research found that Tougu Xiaotong Capsules can be used not only for the treatment of osteoarthritis,but also for rheumatoid arthritis and gouty arthritis.However,the specific mechanism of action of"Same Treatment for Different Diseases"is still unclear.OBJECTIVE:To identify the main effects and mechanisms of Tougu Xiaotong Capsules in the treatment of osteoarthritis,rheumatoid arthritis and gouty arthritis with the treating principle of"Same Treatment for Different Diseases"by the methodologies of integrated pharmacology,molecular docking techniques and molecular dynamics simulation.METHODS:The active chemical components of Tougu Xiaotong Capsules and their corresponding targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and the Swiss Target Prediction database.The disease genes for osteoarthritis,rheumatoid arthritis and gouty arthritis were obtained from the GeneCards and OMIM databases.Cytoscape 3.7.2 software was used to construct a drug-component-disease-target network diagram and a protein-protein interaction network.Gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were conducted using the Daivd database.Molecular docking simulations were performed on the CB-DOCK2 website,and molecular dynamics simulations were carried out using the GROMACS 2020.6 software.RESULTS AND CONCLUSION:(1)A total of 50 active components of Tougu Xiaotong Capsules were screened,with 184 potential targets and 29 intersection targets across the three types of arthritis.(2)The gene ontology enrichment analysis of the intersection targets indicated that the key gene functions of Tougu Xiaotong Capsules in treating the three types of arthritis were found to be cellular response to lipopolysaccharide,inflammatory response,extracellular matrix,protein binding,and zinc ion binding.(3)Kyoto Encyclopedia of Genes and Genomes enrichment analysis identified key pathways as interleukin-17 signaling pathway,tumor necrosis factor signaling pathway,NOD-like receptor and Toll-like receptor signaling pathways.(4)Six core targets[interleukin-6,interleukin-1β,prostaglandin endoperoxide synthase 1,prostaglandin endoperoxide synthase 2,cytochrome P450 1A2(CYP1A2)and C-X-C chemokine ligand 8]were determined based on the protein-protein interaction network.(5)Molecular docking results confirmed that(+)-catechin,β-sitosterol,kaempferol,myricetin,and wallichilide had good structure-activity relationships.Molecular dynamics simulations further confirmed the stable binding of CYP1A2 with wallichilide,corroborating the network pharmacology and molecular docking results.Therefore,Tougu Xiaotong Capsules may regulate the interleukin-17 signaling pathway,tumor necrosis factor signaling pathway,and other signaling pathways by targeting interleukin-1β,prostaglandin endoperoxide synthase 1,prostaglandin endoperoxide synthase 2 and CYP1A2,exert an effect of"Same Treatment for Different Diseases"on osteoarthritis,rheumatoid arthritis and gouty arthritis.

Objective:To construct logistic regression, decision tree, and neural network models to predict pressure injury in neurocritically ill patients using machine learning algorithms, and compare the predictive performance of the three models.Methods:The clinical data of 341 neurocritically ill patients who received treatment in the Department of Neurosurgery at The First Affiliated Hospital of Wenzhou Medical University from May 2020 to February 2023 were collected retrospectively. The patients were randomly divided into a training set and a testing set in a 7:3 ratio. Univariate and multivariate analyses were conducted based on the clinical data from the training set. According to the results of the multivariate analysis, logistic regression, decision tree, and neural network models were constructed. The predictive performance of the three models was validated and compared using receiver operating characteristic curve analysis.Results:Among the 341 patients, 35 developed pressure injury (a total of 40 occurrences), with an incidence rate of 10.26%. Multivariate analysis indicated that incontinence ( OR = 47.32, 95% CI: 1.360-1 647.700), decreased albumin levels ( OR = 0.56, 95% CI: 0.360-0.870), increased sensory ability ( OR = 0.00, 95% CI: 0.000-0.190), and increased mobility ( OR = 0.03, 95% CI: 0.000-0.390) were independent risk factors for pressure injury in neurocritically ill patients (all P < 0.05). Based on these independent risk factors, logistic regression, decision tree, and neural network models were constructed. Receiver operating characteristic curve analysis revealed that the area under the curve for the three models was 0.987 (95% CI: 0.941-0.999), 0.945 (95% CI: 0.881-0.980), and 0.908 (95% CI: 0.834-0.956), respectively. These results suggest that all three models exhibited high predictive performance for pressure injury in neurocritically ill patients, with the logistic regression model showing a significantly greater area under the curve than the neural network model. Conclusions:The occurrence of pressure injury in neurocritically ill patients is closely related to incontinence, albumin levels, sensory ability, and mobility. Constructing predictive models using machine learning algorithms can provide valuable insights for the early prevention and management of pressure injury in neurocritically ill patients.

Objective:To describe the safety of using the Chinese-made robotic laparoscopic surgery system for laparoscopic sacrocolpopexy in the treatment of severe pelvic organ prolapse.Methods:A pilot descriptive clinical study was conducted, enrolling 16 severe pelvic organ prolapse patients at Peking University First Hospital from April 2023 to January 2024. Patients who consented to participate in this study underwent laparoscopic sacrocolpopexy for severe pelvic organ prolapse using Chinese-made robotic laparoscopic surgery system. Preoperative clinical basic data and perioperative data of the patients were collected, summarizing the data on perioperative bleeding and complications, and reviewed the surgical learning experience. The evaluation indicators related to the learning experience included: (1) efficiency evaluation: including equipment docking time, total surgery time, suturing time, mechanical arm operation time and hysterectomy time, which were timed and recorded during surgery; (2) equipment operability evaluation: including equipment operation task load assessment and intraoperative operation feeling score. The cumulative sum analysis method was used to quantify surgery time and fit the learning curve.Results:Sixteen patients were successfully enrolled and underwent surgery, including total hysterectomy with bilateral salpingo-oophorectomy or salpingectomy plus sacrocolpopexy, or sacrocolpopexy alone (for one case without uterus). The age of 16 cases was (56.7±7.6) years (ranged from 44 to 67 years), with body mass index of (25.4±2.5) kg/m2. Concurrent procedures included anterior vaginal wall repair in 12 cases (12/16), posterior vaginal wall repair in 13 cases (13/16), tension-free vaginal tape obturator system in 1 case (1/16), and recto-uterine pouch hernia repair in 4 cases (4/16). The total surgery time was (355.8±91.1) minutes, with docking time at (6.7±4.9) minutes, robotic operative time at (267.6±81.4) minutes, robotic suturing time at (155.6±53.9) minutes, and hysterectomy time at (112.0±45.3) minutes. Learning curve analysis revealed inflection points at 6 cases for total surgery time ( P<0.001, R2=0.944) and robotic operative time ( P<0.001, R2=0.982), 5 cases for docking time ( P<0.001, R2=0.989), and 6 cases for robotic suturing time ( P<0.001, R2=0.907). Hysterectomy time had an inflection point at 5 cases ( P=0.023, R2=0.700). Median blood loss was 30 ml (range: 10-1 000 ml), with severe bleeding in one patient (1/16). No conversions to open surgery or laparoscopy occurred, and no severe perioperative or postoperative complications were reported. Conclusion:The Chinese-made robotic laparoscopic surgery system demonstrates excellent short-time safety and ease of operation for laparoscopic sacrocolpopexy.

Objective:To construct logistic regression, decision tree, and neural network models to predict pressure injury in neurocritically ill patients using machine learning algorithms, and compare the predictive performance of the three models.Methods:The clinical data of 341 neurocritically ill patients who received treatment in the Department of Neurosurgery at The First Affiliated Hospital of Wenzhou Medical University from May 2020 to February 2023 were collected retrospectively. The patients were randomly divided into a training set and a testing set in a 7:3 ratio. Univariate and multivariate analyses were conducted based on the clinical data from the training set. According to the results of the multivariate analysis, logistic regression, decision tree, and neural network models were constructed. The predictive performance of the three models was validated and compared using receiver operating characteristic curve analysis.Results:Among the 341 patients, 35 developed pressure injury (a total of 40 occurrences), with an incidence rate of 10.26%. Multivariate analysis indicated that incontinence ( OR = 47.32, 95% CI: 1.360-1 647.700), decreased albumin levels ( OR = 0.56, 95% CI: 0.360-0.870), increased sensory ability ( OR = 0.00, 95% CI: 0.000-0.190), and increased mobility ( OR = 0.03, 95% CI: 0.000-0.390) were independent risk factors for pressure injury in neurocritically ill patients (all P < 0.05). Based on these independent risk factors, logistic regression, decision tree, and neural network models were constructed. Receiver operating characteristic curve analysis revealed that the area under the curve for the three models was 0.987 (95% CI: 0.941-0.999), 0.945 (95% CI: 0.881-0.980), and 0.908 (95% CI: 0.834-0.956), respectively. These results suggest that all three models exhibited high predictive performance for pressure injury in neurocritically ill patients, with the logistic regression model showing a significantly greater area under the curve than the neural network model. Conclusions:The occurrence of pressure injury in neurocritically ill patients is closely related to incontinence, albumin levels, sensory ability, and mobility. Constructing predictive models using machine learning algorithms can provide valuable insights for the early prevention and management of pressure injury in neurocritically ill patients.

BACKGROUND:Our previous research found that Tougu Xiaotong Capsules can be used not only for the treatment of osteoarthritis,but also for rheumatoid arthritis and gouty arthritis.However,the specific mechanism of action of"Same Treatment for Different Diseases"is still unclear.OBJECTIVE:To identify the main effects and mechanisms of Tougu Xiaotong Capsules in the treatment of osteoarthritis,rheumatoid arthritis and gouty arthritis with the treating principle of"Same Treatment for Different Diseases"by the methodologies of integrated pharmacology,molecular docking techniques and molecular dynamics simulation.METHODS:The active chemical components of Tougu Xiaotong Capsules and their corresponding targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and the Swiss Target Prediction database.The disease genes for osteoarthritis,rheumatoid arthritis and gouty arthritis were obtained from the GeneCards and OMIM databases.Cytoscape 3.7.2 software was used to construct a drug-component-disease-target network diagram and a protein-protein interaction network.Gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were conducted using the Daivd database.Molecular docking simulations were performed on the CB-DOCK2 website,and molecular dynamics simulations were carried out using the GROMACS 2020.6 software.RESULTS AND CONCLUSION:(1)A total of 50 active components of Tougu Xiaotong Capsules were screened,with 184 potential targets and 29 intersection targets across the three types of arthritis.(2)The gene ontology enrichment analysis of the intersection targets indicated that the key gene functions of Tougu Xiaotong Capsules in treating the three types of arthritis were found to be cellular response to lipopolysaccharide,inflammatory response,extracellular matrix,protein binding,and zinc ion binding.(3)Kyoto Encyclopedia of Genes and Genomes enrichment analysis identified key pathways as interleukin-17 signaling pathway,tumor necrosis factor signaling pathway,NOD-like receptor and Toll-like receptor signaling pathways.(4)Six core targets[interleukin-6,interleukin-1β,prostaglandin endoperoxide synthase 1,prostaglandin endoperoxide synthase 2,cytochrome P450 1A2(CYP1A2)and C-X-C chemokine ligand 8]were determined based on the protein-protein interaction network.(5)Molecular docking results confirmed that(+)-catechin,β-sitosterol,kaempferol,myricetin,and wallichilide had good structure-activity relationships.Molecular dynamics simulations further confirmed the stable binding of CYP1A2 with wallichilide,corroborating the network pharmacology and molecular docking results.Therefore,Tougu Xiaotong Capsules may regulate the interleukin-17 signaling pathway,tumor necrosis factor signaling pathway,and other signaling pathways by targeting interleukin-1β,prostaglandin endoperoxide synthase 1,prostaglandin endoperoxide synthase 2 and CYP1A2,exert an effect of"Same Treatment for Different Diseases"on osteoarthritis,rheumatoid arthritis and gouty arthritis.

Objective: The study aimed to investigate the role of N6-methyladenosine (m6A) modification in spinal cord injury (SCI) and its underlying mechanism, focusing on the interplay between m6A methyltransferase-like 3 (METTL3), miR-30c, and autophagy-related proteins. Methods: An SCI model was established in rats, and changes in autophagy-related proteins, m6A methylation levels, and miR-30c levels were analyzed. Hydrogen peroxide (H2O2)-stimulated spinal cord neuron cells (SCNCs) were used to assess the impact of METTL3 overexpression. The effects of STM2457, an antagonist of METTL3, were evaluated on cell viability, apoptosis, and autophagy markers in H2O2-stimulated SCNCs. Results: In the SCI model, decreased levels of autophagy markers and increased m6A methylation, miR-30c levels, and METTL3 were observed. Overexpression of METTL3 in SCNCs led to reduced cell viability, increased apoptosis, and suppressed autophagy. Conversely, co-overexpression of autophagy-related protein 5 (ATG5) or miR-30c inhibition reversed these effects. Knocking out METTL3 yielded opposite results. STM2457 treatment improved cell viability, reduced apoptosis, and upregulated autophagy markers in SCNCs, which also enhanced functional recovery in rats as measured by the Basso-Beattie-Bresnahan score and inclined plate test. Conclusion STM2457 alleviated SCI by suppressing METTL3-mediated m6A modification of miR-30c, which in turn induces ATG5-mediated autophagy. This study provides insights into the role of m6A modification in SCI and suggests a potential therapeutic approach through targeting METTL3.

Objective:To investigate the psychological status of HD nursing staff in hospitals in Guangdong province and its influential factors.Methods:1 630 nursing staff in HD rooms of 71 hospitals or units in Guangdong Province in February and March 2020 were evaluated by using the 10-item Kessler psychological distress scale (Kessler 10), General self-efficacy scale (GSES) and Connor-Davidson resilience scale (CD-RISC) to conduct a questionnaire survey on their psychological status. Insomnia severity index (ISI) and Fatigue scale-14 (FS-14) were used to investigate their degree of insomnia and fatigue. General information on gender, age, educational level, marital status, economic income, professional title, HD working hours, average weekly overtime times and hours, total number of HD patients per day, and whether holding other positions were collected.Results:A total of 1 630 questionnaires were collected, among which 1 629 were valid, with an effective recovery rate of 99.9%. The scores of the three scales were (20.16±7.47), (27.03±4.45) and (58.37±15.75), respectively. According to the Kessler 10, 835 people (51.2%) had mental disorders. Univariate analysis showed that age, educational level, economic income, type of work unit, total number of HD patients per day and living status in recent one week were related with Kessler 10 score (all P<0.05). Economic income, type of work unit, whether holding other positions, total number of HD patients per day and living status in recent one week were related with GSES scores (all P<0.05). Age, marital status, economic income, professional title, type of work unit, whether holding other positions and living status in recent one week were related to CD-RISC score (all P<0.05). Spearman rank correlation analysis showed that the number of HD machines ( r=0.100, P<0.001), the number of nurses ( r=0.082, P=0.001), average weekly overtime times ( r=0.142, P<0.001) and overtime hours ( r=0.136, P<0.001), ISI score ( r=0.572, P<0.001) and FS-14 score ( r=0.635, P<0.001) were correlated with Kessler 10 score. ISI score ( r=-0.311, P<0.001) and FS-14 score ( r=-0.335, P<0.001) were correlated with GSES score. Working years of HD service ( r=0.112, P<0.001), ISI score ( r=-0.289, P<0.001) and FS-14 score ( r=-0.314, P<0.001) were correlated with CD-RISC score. Multiple linear regression analysis showed that the economic income in 5 001-10 000 yuan (with<3 000 yuan as reference, B=-1.603, 95% CI -3.036--0.169, P=0.028) and the total number of HD patients per day >200 (with ≤50 as reference, B=-1.153, 95% CI -2.242--0.065, P=0.038) were negatively correlated with Kessler 10 score, and average weekly overtime times ( B=0.221, 95% CI 0.069-0.374, P=0.004), ISI score ( B=0.518, 95% CI 0.454-0.582, P<0.001) and FS-14 score ( B=1.166, 95% CI 1.066-1.265, P<0.001) were positively correlated with Kessler 10 score. The economic income (with<3 000 yuan as reference) in 3 001-5 000 yuan ( B=1.930, 95% CI 0.847-3.013, P<0.001), 5 001-10 000 yuan ( B=1.949, 95% CI 0.887-3.012, P<0.001), 10 001-15 000 yuan ( B=1.482, 95% CI 0.318-2.647, P=0.013), >20 000 yuan ( B=4.300, 95% CI 2.463-6.136, P<0.001), secondary hospital (with primary hospitals as reference, B= 1.078, 95% CI 0.005-2.152, P=0.049) and holding other positions ( B=0.729, 95% CI 0.277-1.181, P=0.002) were positively correlated with GSES score, and ISI score ( B=-0.169, 95% CI -0.217--0.120, P<0.001) and FS-14 score ( B=-0.403, 95% CI -0.478--0.328, P<0.001) were negatively correlated with GSES score. The economic income (with<3 000 yuan as reference) in 3 001-5 000 yuan ( B=7.631, 95% CI 3.753-11.509, P<0.001), 5 001-10 000 yuan ( B=9.236, 95% CI 5.362-13.110, P<0.001), 10 001-15 000 yuan ( B=9.039, 95% CI 4.735-13.342, P<0.001), 15 001-20 000 yuan ( B=8.639, 95% CI 2.989-14.289, P=0.003), >20 000 yuan ( B=16.101, 95% CI 9.162-23.039, P<0.001) and holding other positions ( B=3.228, 95% CI 1.510-4.945, P<0.001) were positively correlated with CD-RISC score, and ISI score ( B=-0.593, 95% CI -0.765--0.420, P<0.001) and FS-14 score ( B=-1.258, 95% CI -1.525--0.992, P<0.001) were negatively correlated with CD-RISC score. Conclusion:The psychological status of nursing staff in HD rooms of hospitals in Guangdong Province needs to be improved. Effective preventive measures should be taken to provide timely psychological support, counseling and intervention to nursing staff with psychological abnormalities, and encourage them to take the initiative to seek psychological counseling when necessary, so as to promote their physical and mental health.