ObjectiveTo clarify whether METTL14 mediates the core role of acupuncture at Neiguan (PC6) in promoting myelination and improving behavior in young autistic rats through gene intervention technology. MethodsThe ASD model was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats. Male offspring were intracerebroventricularly injected with adenovirus-packaged METTL14 shRNA (sh-METTL14) or its control (sh-NC) on postnatal day 1, with a model group set as well. Subsequently, the juvenile rats were divided into model group, acupuncture group, acupuncture+sh-NC group, and acupuncture+sh-METTL14 group. The acupuncture group received acupuncture at Neiguan (PC6) from postnatal day 7, once daily for 21 consecutive days. Neurobehavioral changes were evaluated by behavioral tests; METTL14 knockdown efficiency and the expression of METTL14, METTL3, and PTEN were detected by quantitative real-time PCR (qRT-PCR) and Western blot (WB); PTEN m⁶A levels were measured by RNA immunoprecipitation-qPCR (RIP-qPCR); myelin ultrastructure, expression of myelin basic protein (MBP) and neurofascin 155 (NF155), and dendritic spine density were observed using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, qRT-PCR, and primary neuron culture. ResultsBehaviorally, knockdown of METTL14 significantly counteracted the beneficial effects of acupuncture in improving self-grooming, open field exploration, three-chamber social interaction, and Morris water maze learning and memory (P<0.05, P<0.01). Compared with the acupuncture+sh-NC group, the acupuncture+sh-METTL14 group showed significantly decreased mRNA and protein expression of hippocampal METTL14 (P<0.01), and the upregulating effects of acupuncture on METTL3 and PTEN expression were reversed (P<0.01). Meanwhile, knockdown of METTL14 significantly inhibited the acupuncture-induced increase in PTEN m⁶A levels (P<0.01). Morphologically, knockdown of METTL14 attenuated the improvement of myelin structure by acupuncture, reversed the downregulation of MBP and upregulation of NF155 induced by acupuncture, and blocked the increase in dendritic spine density (P<0.05, P<0.01). ConclusionMETTL14 is a key molecule mediating the therapeutic effect of acupuncture at Neiguan. Acupuncture at Neiguan upregulates METTL14, thereby enhancing m⁶A methylation modification of PTEN mRNA to stabilize its expression, ultimately promoting myelin development and improving behavioral symptoms in ASD juvenile rats. This preliminarily reveals the modern biological connotation of “opening Xuanfu and dredging myelin”.

ObjectiveTo clarify whether METTL14 mediates the core role of acupuncture at Neiguan (PC6) in promoting myelination and improving behavior in young autistic rats through gene intervention technology. MethodsThe ASD model was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats. Male offspring were intracerebroventricularly injected with adenovirus-packaged METTL14 shRNA (sh-METTL14) or its control (sh-NC) on postnatal day 1, with a model group set as well. Subsequently, the juvenile rats were divided into model group, acupuncture group, acupuncture+sh-NC group, and acupuncture+sh-METTL14 group. The acupuncture group received acupuncture at Neiguan (PC6) from postnatal day 7, once daily for 21 consecutive days. Neurobehavioral changes were evaluated by behavioral tests; METTL14 knockdown efficiency and the expression of METTL14, METTL3, and PTEN were detected by quantitative real-time PCR (qRT-PCR) and Western blot (WB); PTEN m⁶A levels were measured by RNA immunoprecipitation-qPCR (RIP-qPCR); myelin ultrastructure, expression of myelin basic protein (MBP) and neurofascin 155 (NF155), and dendritic spine density were observed using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, qRT-PCR, and primary neuron culture. ResultsBehaviorally, knockdown of METTL14 significantly counteracted the beneficial effects of acupuncture in improving self-grooming, open field exploration, three-chamber social interaction, and Morris water maze learning and memory (P<0.05, P<0.01). Compared with the acupuncture+sh-NC group, the acupuncture+sh-METTL14 group showed significantly decreased mRNA and protein expression of hippocampal METTL14 (P<0.01), and the upregulating effects of acupuncture on METTL3 and PTEN expression were reversed (P<0.01). Meanwhile, knockdown of METTL14 significantly inhibited the acupuncture-induced increase in PTEN m⁶A levels (P<0.01). Morphologically, knockdown of METTL14 attenuated the improvement of myelin structure by acupuncture, reversed the downregulation of MBP and upregulation of NF155 induced by acupuncture, and blocked the increase in dendritic spine density (P<0.05, P<0.01). ConclusionMETTL14 is a key molecule mediating the therapeutic effect of acupuncture at Neiguan. Acupuncture at Neiguan upregulates METTL14, thereby enhancing m⁶A methylation modification of PTEN mRNA to stabilize its expression, ultimately promoting myelin development and improving behavioral symptoms in ASD juvenile rats. This preliminarily reveals the modern biological connotation of “opening Xuanfu and dredging myelin”.

Trauma is an important cause of death in young- and middle-aged people. Trauma is comprehensive and includes many surgical specialties, and the surgical techniques of these specialties have long been mature. To reduce the mortality and disability rate of trauma patients, it is necessary to improve trauma management. Trauma has attracted attention in China and trauma treatment and care developed rapidly in recent years. To decrease traumatic mortality and disability rates, our team is committed to building an efficient trauma system in Shaanxi province and has successfully developed a trauma limb salvage map to address the high rates of amputation and disability in patients with limb injuries. This article elaborates on the construction experience of a trauma limb salvage map and its application details in Shaanxi province of China.
Humans ; China ; Limb Salvage/methods* ; Wounds and Injuries/surgery* ; Male ; Extremities/injuries* ; Adult ; Amputation, Surgical ; Middle Aged ; Female

OBJECTIVES: To explore the mediating role of sleep duration in the relationship between depression symptoms and myopia among middle school students. METHODS: This study was a cross-sectional research conducted using a stratified cluster random sampling method. A total of 1 728 middle school students were selected from two junior high schools and two senior high schools in certain urban areas and farms of the Xinjiang Production and Construction Corps. Questionnaire surveys and vision tests were conducted among the students. Spearman analysis was used to analyze the correlation between depression symptoms, sleep duration, and myopia. The Bootstrap method was employed to investigate the mediating effect of sleep duration between depression symptoms and myopia. RESULTS: The prevalence of myopia in the overall population was 74.02% (1 279/1 728), with an average sleep duration of (7.6±1.0) hours. The rate of insufficient sleep was 83.62% (1 445/1 728), and the proportion of students exhibiting depression symptoms was 25.29% (437/1 728). Correlation analysis showed significant negative correlations between visual acuity in both eyes and sleep duration with depressive emotions as measured by the Center for Epidemiologic Studies Depression Scale (with correlation coefficients of -0.064, -0.084, and -0.199 respectively; P<0.01), as well as with somatic symptoms and activities (with correlation coefficients of -0.104, -0.124, and -0.233 respectively; P<0.01) and interpersonal relationships (with correlation coefficients of -0.052, -0.059, and -0.071 respectively; P<0.05). The correlation coefficients for left and right eye visual acuity and sleep duration were 0.206 and 0.211 respectively (P<0.001). Sleep duration exhibited a mediating effect between depression symptoms and myopia (indirect effect=0.056, 95%CI: 0.029-0.088), with the mediating effect value for females (indirect effect=0.066, 95%CI: 0.024-0.119) being higher than that for males (indirect effect=0.042, 95%CI: 0.011-0.081). CONCLUSIONS Sleep duration serves as a partial mediator between depression symptoms and myopia in middle school students.
Humans ; Myopia/etiology* ; Male ; Female ; Depression/physiopathology* ; Cross-Sectional Studies ; Sleep ; Adolescent ; Students ; Child ; Time Factors ; Sleep Duration

ObjectiveMicrotube associated protein-2 （MAP-2）， alpha-tubulin （α-tubulin）， and synaptophysin （SYP） are important proteins in neuronal signal communication. This paper observed the effects of modified Zhigancao Tang on the expression of serum α-Synuclein （α-Syn） and its oligomers， MAP-2， α-tubulin， and SYP of patients with liver and kidney deficiency of Parkinson's disease （PD）， analyzed their correlation， and evaluated the therapeutic effect of modified Zhigancao Tang in patients with liver and kidney deficiency of PD based on α-Syn transmission pathway mediated by neuronal communication in vivo. MethodsA total of 60 patients with PD who met the inclusion criteria were randomly divided into a treatment group （30 cases） and a control group （30 cases）. Both groups were treated on the basis of PD medicine， and the treatment group was treated with modified Zhigancao Tang. Both groups were treated for 12 weeks. The changes in UPDRS score， TCM syndrome score， and expression of serum α-Syn and its oligomers， MAP-2， α-tubulin， and SYP were observed before and after 12 weeks of treatment in each group. The correlation between the above-mentioned serum biological indexes and the levels of serum α-Syn and its oligomers was analyzed. ResultsAfter treatment， the TCM syndrome score， UPDRS score， UPDRS-Ⅱ score， and UPDRS-Ⅲ score of the treatment group were significantly decreased （P<0.05， P<0.01）. The UPDRS score， UPDRS-Ⅱ score， and UPDRS-Ⅲ scores in the treatment group were significantly decreased compared with those in the control group after treatment （P<0.05）. After treatment， the total effective rate of the control group was 63.3% （19/30）， and that of the treatment group was 86.7% （26/30）. The clinical effect of the observation group was better than the control group （Z=-2.03， P<0.05）. The total effective rate of the observation group was better than that of the control group， and the difference was statistically significant （χ²=5.136， P<0.05）. After treatment， the oligomer level of serum α-Syn and MAP-2 level in the treatment group were significantly decreased （P<0.05， P<0.01）. The levels of serum α-Syn and its oligomers， as well as α-tubulin in the treatment group， were significantly decreased compared with those in the control group after treatment （P<0.05， P<0.01）. Serum α-Syn was correlated with serum MAP-2 and α-Syn oligomer in patients with PD （P<0.05， P<0.01） but not correlated with serum SYP . Serum α-Syn oligomers of patients with PD were correlated with serum MAP-2 and α-tubulin （P<0.05， P<0.01） but not correlated with serum SYP level. Serum SYP of patients with PD was correlated with serum MAP-2 （P<0.05）. ConclusionModified Zhigancao Tang has a therapeutic effect on patients with liver and kidney deficiency of PD by inhibiting the production of α-Syn oligomers and intervening α-Syn microtubule transport pathway in vivo.

Objective:To investigate the factors influencing early recurrence for patients with initially unresectable hepatocellular carcinoma (HCC) who underwent salvage liver resection (SLR) following transcatheter arterial chemoembolization-based downstaging treatment, and construct a predictive model to evaluate its predicting performance.Methods:The retrospective cohort study was constructed. The clinicopathological data of 305 patients with initially unresectable HCC who were admitted to 4 medical centers in China, including the Third Affiliated Hospital of Naval Medical University (Shanghai Eastern Hepatobiliary Surgery Hospital) et al, from January 2019 to December 2021 were collected. There were 286 males and 19 females, aged (48.7±10.4)years. A total of 133 patients who were admitted from January 2019 to December 2020 were set as the training cohort, and the other 172 patients who were admitted from January to December 2021 were set as the validation cohort. Observation indicators: (1) postoperative recurrence-free survival in HCC patients; (2) analysis of factors influencing postoperative early recurrence in HCC patients; (3) construction and validation of the predictive model. Comparison of measurement data with normal distribution between groups was conducted using the independent sample t test. Comparison of count data between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the rank sum test. Univariate and multivariate analyses were conducted using the Cox regre-ssion model. The Kaplan-Meier method was used to calculate survival. The Log-rank test was used for survival analysis. The predicting performance of the model was evaluated using the concordance index (C-index) and the area under curve (AUC) of time-dependent receiver operating characteristic (ROC) curve, and the accuracy of the model was validated using the calibration curve. The total net gain of the model was evaluated using the decision curve. Results:(1) Postoperative recurrence-free survival in HCC patients. The recurrence-free survival time of 133 HCC patients in the training cohort was 10.0(range, 1.5-24.0)months, with 1-, 2-year recurrence-free survival rate of 47.3% and 36.8%. The recurrence-free survival time of 172 HCC patients in the validation cohort was 11.0(range, 1.0-24.0)months, with 1-, 2-year recurrence-free survival rate of 51.7% and 37.2%. There was no significant difference in recurrence-free survival between patients in the training cohort and the validation cohort ( χ2=0.075, P>0.05). (2) Analysis of factors influencing postoperative early recur-rence in HCC patients. Results of multivariate analysis showed that tumor burden prior to down-staging treatment, grade of albumin-bilirubin (ALBI) score prior to SLR, alpha-fetoprotein (AFP) half-life prior to SLR, and tumor response prior to SLR were independent factors influencing early recurrence in HCC patients after surgery [ hazard ratio=3.212, 2.526, 2.304, 1.575, 95% confidence interal ( CI) as 1.262-8.175, 1.324-4.818, 1.477-3.595, 1.138-2.180, P<0.05]. (3) Construction and validation of the predictive model. A nomogram predictive model for postoperative early recurrence was constructed base on the results of multivariate analysis. The C-index of predictive model was 0.786 for the training cohort and 0.734 for the validation cohort. The AUC of ROC curve of nomogram predictive model for 12-, 18-, and 24-month recurrence-free survival rate in the training cohort were 0.890 (95% CI as 0.836-0.944), 0.895 (95% CI as 0.842-0.947), and 0.887 (95% CI as 0.831-0.942), respectively. The AUC of ROC curve of nomogram predictive model for 12-, 18-, and 24-month recurrence-free survival rate in the validation cohort were 0.845 (95% CI as 0.781-0.909], 0.888 (95% CI as 0.826-0.950), and 0.919 (95% CI as 0.870-0.968), respectively. Results of calibration curve showed high consistency between the predicted results of nomogram predictive model and actual outcomes. Results of decision curve showed the nomogram predictive model with a good total net gain at a threshold of 0.10-0.50. Conclusions:Tumor burden prior to downstaging treatment, grade of ALBI score prior to SLR, AFP half-life prior to SLR, and tumor response prior to SLR are independent factors influencing early recurrence in initially unresectable HCC patients undergoing SLR following downstaging treatment. The nomogram predictive model based on these factors can effectively evaluate the prognosis of this patient population.

Aim To explore the possible regulatory effect of leptin on acyl-CoA synthetase long chain fami-ly member ACSL5 and their effect on migration and in-vasion of breast cancer cell,and to explore the underly-ing mechanism.Methods The expression of leptin receptor was detected by immunofluorescence assay.The migration and invasion ability of MCF-7 cells were detected by wound healing assay and Transwell assay respectively.The downstream target gene of leptin was analyzed by PCR microarray data.The expression of ACSL5 in breast cancer and its correlation with the staging and prognosis of breast cancer patients were as-sessed uing bioinformatics methods.The expression of ACSL5 in MCF-7 cells treated with different concentra-tions of leptin was detected using real time fluorescence quantitative polymerase chain reaction(RT-qPCR).Overexpressing ACSL5 was constructed by lentiviral transfection;the expressions of EMT related proteins,AMPK-α and p-AMPK-α were detected by Western blot.Results Leptin promoted breast cancer cell mi-gration and invasion and EMT.ACSL5 was significant-ly low expressed in breast cancer and related to progno-sis.Leptin downregulated the expression of ACSL5 through OBR.Leptin activated AMPK pathway to downregulate ACSL5 and promote migration,invasion and EMT of breast cancer cells.Conclusions Leptin may promote the migration,invasion and EMT of breast cancer by downregulating ACSL5 through activating AMPK pathway.

Aim To explore the possible regulatory effect of leptin on acyl-CoA synthetase long chain fami-ly member ACSL5 and their effect on migration and in-vasion of breast cancer cell,and to explore the underly-ing mechanism.Methods The expression of leptin receptor was detected by immunofluorescence assay.The migration and invasion ability of MCF-7 cells were detected by wound healing assay and Transwell assay respectively.The downstream target gene of leptin was analyzed by PCR microarray data.The expression of ACSL5 in breast cancer and its correlation with the staging and prognosis of breast cancer patients were as-sessed uing bioinformatics methods.The expression of ACSL5 in MCF-7 cells treated with different concentra-tions of leptin was detected using real time fluorescence quantitative polymerase chain reaction(RT-qPCR).Overexpressing ACSL5 was constructed by lentiviral transfection;the expressions of EMT related proteins,AMPK-α and p-AMPK-α were detected by Western blot.Results Leptin promoted breast cancer cell mi-gration and invasion and EMT.ACSL5 was significant-ly low expressed in breast cancer and related to progno-sis.Leptin downregulated the expression of ACSL5 through OBR.Leptin activated AMPK pathway to downregulate ACSL5 and promote migration,invasion and EMT of breast cancer cells.Conclusions Leptin may promote the migration,invasion and EMT of breast cancer by downregulating ACSL5 through activating AMPK pathway.

Objective:To investigate the factors influencing early recurrence for patients with initially unresectable hepatocellular carcinoma (HCC) who underwent salvage liver resection (SLR) following transcatheter arterial chemoembolization-based downstaging treatment, and construct a predictive model to evaluate its predicting performance.Methods:The retrospective cohort study was constructed. The clinicopathological data of 305 patients with initially unresectable HCC who were admitted to 4 medical centers in China, including the Third Affiliated Hospital of Naval Medical University (Shanghai Eastern Hepatobiliary Surgery Hospital) et al, from January 2019 to December 2021 were collected. There were 286 males and 19 females, aged (48.7±10.4)years. A total of 133 patients who were admitted from January 2019 to December 2020 were set as the training cohort, and the other 172 patients who were admitted from January to December 2021 were set as the validation cohort. Observation indicators: (1) postoperative recurrence-free survival in HCC patients; (2) analysis of factors influencing postoperative early recurrence in HCC patients; (3) construction and validation of the predictive model. Comparison of measurement data with normal distribution between groups was conducted using the independent sample t test. Comparison of count data between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the rank sum test. Univariate and multivariate analyses were conducted using the Cox regre-ssion model. The Kaplan-Meier method was used to calculate survival. The Log-rank test was used for survival analysis. The predicting performance of the model was evaluated using the concordance index (C-index) and the area under curve (AUC) of time-dependent receiver operating characteristic (ROC) curve, and the accuracy of the model was validated using the calibration curve. The total net gain of the model was evaluated using the decision curve. Results:(1) Postoperative recurrence-free survival in HCC patients. The recurrence-free survival time of 133 HCC patients in the training cohort was 10.0(range, 1.5-24.0)months, with 1-, 2-year recurrence-free survival rate of 47.3% and 36.8%. The recurrence-free survival time of 172 HCC patients in the validation cohort was 11.0(range, 1.0-24.0)months, with 1-, 2-year recurrence-free survival rate of 51.7% and 37.2%. There was no significant difference in recurrence-free survival between patients in the training cohort and the validation cohort ( χ2=0.075, P>0.05). (2) Analysis of factors influencing postoperative early recur-rence in HCC patients. Results of multivariate analysis showed that tumor burden prior to down-staging treatment, grade of albumin-bilirubin (ALBI) score prior to SLR, alpha-fetoprotein (AFP) half-life prior to SLR, and tumor response prior to SLR were independent factors influencing early recurrence in HCC patients after surgery [ hazard ratio=3.212, 2.526, 2.304, 1.575, 95% confidence interal ( CI) as 1.262-8.175, 1.324-4.818, 1.477-3.595, 1.138-2.180, P<0.05]. (3) Construction and validation of the predictive model. A nomogram predictive model for postoperative early recurrence was constructed base on the results of multivariate analysis. The C-index of predictive model was 0.786 for the training cohort and 0.734 for the validation cohort. The AUC of ROC curve of nomogram predictive model for 12-, 18-, and 24-month recurrence-free survival rate in the training cohort were 0.890 (95% CI as 0.836-0.944), 0.895 (95% CI as 0.842-0.947), and 0.887 (95% CI as 0.831-0.942), respectively. The AUC of ROC curve of nomogram predictive model for 12-, 18-, and 24-month recurrence-free survival rate in the validation cohort were 0.845 (95% CI as 0.781-0.909], 0.888 (95% CI as 0.826-0.950), and 0.919 (95% CI as 0.870-0.968), respectively. Results of calibration curve showed high consistency between the predicted results of nomogram predictive model and actual outcomes. Results of decision curve showed the nomogram predictive model with a good total net gain at a threshold of 0.10-0.50. Conclusions:Tumor burden prior to downstaging treatment, grade of ALBI score prior to SLR, AFP half-life prior to SLR, and tumor response prior to SLR are independent factors influencing early recurrence in initially unresectable HCC patients undergoing SLR following downstaging treatment. The nomogram predictive model based on these factors can effectively evaluate the prognosis of this patient population.

Objective:To investigate respiratory virus infection in children with septic shock in pediatric care units (PICU) in China and its influence on clinical outcomes.Methods:The clinical data of children with septic shock in children′s PICU from January 2018 to December 2019 in 10 Chinese hospitals were retrospectively collected. They were divided into the pre-COVID-19 and post-COVID-19 groups according to the onset of disease, and the characteristics and composition of respiratory virus in the 2 groups were compared. Matching age, malignant underlying diseases, bacteria, fungi and other viruses, a new database was generated using 1∶1 propensity score matching method. The children were divided into the respiratory virus group and non-respiratory virus group according to the presence or absence of respiratory virus infection; their clinical characteristics, diagnosis, and treatment were compared by t-test, rank sum test and Chi-square test. The correlation between respiratory virus infection and the clinical outcomes was analyzed by logistic regression. Results:A total of 1 247 children with septic shock were included in the study, of them 748 were male; the age was 37 (11, 105) months. In the pre-and post-COVID-19 groups, there were 530 and 717 cases of septic shock, respectively; the positive rate of respiratory virus was 14.9% (79 cases) and 9.8% (70 cases); the seasonal distribution of septic shock was 28.9% (153/530) and 25.9% (185/717) in autumn, and 30.3% (161/530) and 28.3% (203/717) in winter, respectively, and the corresponding positive rates of respiratory viruses were 19.6% (30/153) and 15.7% (29/185) in autumn, and 21.1% (34/161) and 15.3% (31/203) in winter, respectively. The positive rates of influenza virus and adenovirus in the post-COVID-19 group were lower than those in the pre-COVID-19 group (2.1% (15/717) vs. 7.5% (40/530), and 0.7% (5/717) vs. 3.2% (17/530), χ2=21.51 and 11.08, respectively; all P<0.05). Rhinovirus virus were higher than those in the pre-Covid-19 group (1.7% (12/717) vs. 0.2% (1/530), χ2=6.51, P=0.011). After propensity score matching, there were 147 cases in both the respiratory virus group and the non-respiratory virus group. Rate of respiratory failure, acute respiratory distress, rate of disseminated coagulation dysfunction, and immunoglobulin usage of the respiratory virus group were higher than those of non-respiratory virus group (77.6% (114/147) vs. 59.2% (87/147), 17.7% (26/147) vs. 4.1% (6/147), 15.6% (25/147) vs. 4.1% (7/147), and 35.4% (52/147) vs. 21.4% (32/147); χ2=11.07, 14.02, 11.06 and 6.67, all P<0.05); and PICU hospitalization of the former was longer than that of the later (7 (3, 16) vs. 3 (1, 7)d, Z=5.01, P<0.001). Univariate logistic regression analysis showed that the presence of respiratory viral infection was associated with respiratory failure, disseminated coagulation dysfunction, the use of mechanical ventilation, and the use of immunoglobulin and anti-respiratory viral drugs ( OR=2.42, 0.22, 0.25, 0.56 and 1.12, all P<0.05). Conclusions:The composition of respiratory virus infection in children with septic shock is different between pre and post-COVID-19. Respiratory viral infection is associated with organ dysfunction in children with septic shock. Decreasing respiratory viral infection through respiratory protection may improve the clinical outcome of these children.