BACKGROUND:There are many problems to completely transform clinical diseases into animal models,but the ideal animal model is the premise of the mechanism research of cervical spondylosis,and it is very important to select the appropriate animal model of cervical spondylosis.OBJECTIVE:To analyze the species,sex,age,type of cervical spondylosis model and its internal molecular mechanism of animal models of cervical spondylosis in detail so as to explore how to select suitable animal models for experimental research of cervical spondylosis.METHODS:PubMed,Medline,Embase,Web of Science,WanFang,VIP,and CNKI databases were searched with Chinese and English search terms"cervical spondylosis,cervical spondylotic myelopathy,cervical spondylotic radiculopathy,cervical spondylosis of vertebral artery type,neck type cervical spondylosis,unbalanced dynamic and static forces,joint injury,neck pain,animal model."According to the inclusion and exclusion criteria,the literature was screened,and finally 61 articles were included for review and analysis.RESULTS AND CONCLUSION:Rats are the most commonly used animals,and males seem to be more popular.It is recommended to use young adult animals.According to the characteristics of molding,cervical spondylosis models were divided into cervical spondylotic myelopath,cervical spondylotic radiculopathy,neck type cervical spondylosis,and other type cervical spondylosis.The advantages and disadvantages of various modeling methods were evaluated.Based on the studies of existing animal models,the molecular mechanism of cervical spondylosis was summarized.Therapeutic signals mediate nuclear factor-κB,phosphatidylinositol-3 kinase/protein kinase B,mitogen-activated protein kinase,and other pathways to regulate the biological processes of inflammation,apoptosis and autophagy of spinal cord,nerve root,intervertebral disc,muscle and other tissues,and ultimately delay the progression of cervical spondylosis.The quality of some studies is poor,and the clinical compatibility is not high.In the future,it is necessary to further standardize the animal model of cervical spondylosis,formulate relevant guidelines,improve the credibility of the research results,and lay a solid foundation for further human clinical trials.

Objective:To explore the results of four types of Urea cycle disorders (UCDs) in newborns from the Xuzhou region, assess the efficacy of newborn screening by tandem mass spectrometry (MS/MS), and analyze their genetic characteristics.Methods:A retrospective analysis was performed using tandem mass spectrometry to screen for inherited metabolic disorders in 691 712 newborns at the Maternal and Child Health Care Hospital of Xuzhou from November 2015 to December 2023. Ten children (cases 1-10) were diagnosed with Ornithine transcarbamylase deficiency (OTCD), Carbamoylphosphate synthase 1 deficiency (CPS1D), Arginase deficiency (ARGD), and Argininosuccinate synthase deficiency (ASSD) based on MS/MS and genetic testing. This study was approved by the Medical Ethics Committee of Xuzhou Maternity and Child Health Care Hospital (Ethics No.XZFY2024-051K-01J).Results:A total of 691 712 neonates were screened for UCDs using MS/MS, which identified 1 237, 1 237, 510, and 1 009 initial positive cases for OTCD, CPS1D, ASSD, and ARGD, respectively. After genetic testing, 1 case of OTCD, 1 case of CPS1D, 1 case of ASSD, and 7 cases of ARGD were confirmed. The overall positive predictive value for these four UCDs was 0.362%. Among the 10 diagnosed UCD cases, four novel variants were identified, which included OTC: c. 1024C>A (p.L342M) and ASS1: c. 826A>G (p.M276V), c.695C>T (p.P232L) and c. 694C>T (p.P232S). Bioinformatic analysis has rated these as variants of uncertain clinical significance or likely pathogenic based on guidelines from the American College of Medical Genetics and Genomics (ACMG). Conclusion:The incidence of four UCDs in neonates from the Xuzhou area is relatively low, and there is a correlation between genetic variants and clinical phenotypes. For novel variants with uncertain clinical significance or suspected pathogenicity, their pathogenicity should be clarified in conjunction with clinical and biochemical indicators. The four novel pathogenic variants of UCDs identified in this study have enriched the mutational spectrum of UCDs-associated genes in the Xuzhou region.

OBJECTIVE: To explore the results of four types of Urea cycle disorders (UCDs) in newborns from the Xuzhou region, assess the efficacy of newborn screening by tandem mass spectrometry (MS/MS), and analyze their genetic characteristics. METHODS: A retrospective analysis was performed using tandem mass spectrometry to screen for inherited metabolic disorders in 691 712 newborns at the Maternal and Child Health Care Hospital of Xuzhou from November 2015 to December 2023. Ten children (cases 1-10) were diagnosed with Ornithine transcarbamylase deficiency (OTCD), Carbamoylphosphate synthase 1 deficiency (CPS1D), Arginase deficiency (ARGD), and Argininosuccinate synthase deficiency (ASSD) based on MS/MS and genetic testing. This study was approved by the Medical Ethics Committee of Xuzhou Maternity and Child Health Care Hospital (Ethics No.XZFY2024-051K-01J). RESULTS: A total of 691 712 neonates were screened for UCDs using MS/MS, which identified 1 237, 1 237, 510, and 1 009 initial positive cases for OTCD, CPS1D, ASSD, and ARGD, respectively. After genetic testing, 1 case of OTCD, 1 case of CPS1D, 1 case of ASSD, and 7 cases of ARGD were confirmed. The overall positive predictive value for these four UCDs was 0.362%. Among the 10 diagnosed UCD cases, four novel variants were identified, which included OTC: c.1024C>A (p.L342M) and ASS1: c.826A>G (p.M276V), c.695C>T (p.P232L) and c.694C>T (p.P232S). Bioinformatic analysis has rated these as variants of uncertain clinical significance or likely pathogenic based on guidelines from the American College of Medical Genetics and Genomics (ACMG). CONCLUSION The incidence of four UCDs in neonates from the Xuzhou area is relatively low, and there is a correlation between genetic variants and clinical phenotypes. For novel variants with uncertain clinical significance or suspected pathogenicity, their pathogenicity should be clarified in conjunction with clinical and biochemical indicators. The four novel pathogenic variants of UCDs identified in this study have enriched the mutational spectrum of UCDs-associated genes in the Xuzhou region.
Humans ; Infant, Newborn ; Tandem Mass Spectrometry/methods* ; Urea Cycle Disorders, Inborn/diagnosis* ; Neonatal Screening/methods* ; Genetic Testing/methods* ; Female ; Retrospective Studies ; Male ; Ornithine Carbamoyltransferase Deficiency Disease/diagnosis* ; Mutation ; Carbamoyl-Phosphate Synthase (Ammonia)/genetics* ; Ornithine Carbamoyltransferase/genetics*

BACKGROUND:There are many problems to completely transform clinical diseases into animal models,but the ideal animal model is the premise of the mechanism research of cervical spondylosis,and it is very important to select the appropriate animal model of cervical spondylosis.OBJECTIVE:To analyze the species,sex,age,type of cervical spondylosis model and its internal molecular mechanism of animal models of cervical spondylosis in detail so as to explore how to select suitable animal models for experimental research of cervical spondylosis.METHODS:PubMed,Medline,Embase,Web of Science,WanFang,VIP,and CNKI databases were searched with Chinese and English search terms"cervical spondylosis,cervical spondylotic myelopathy,cervical spondylotic radiculopathy,cervical spondylosis of vertebral artery type,neck type cervical spondylosis,unbalanced dynamic and static forces,joint injury,neck pain,animal model."According to the inclusion and exclusion criteria,the literature was screened,and finally 61 articles were included for review and analysis.RESULTS AND CONCLUSION:Rats are the most commonly used animals,and males seem to be more popular.It is recommended to use young adult animals.According to the characteristics of molding,cervical spondylosis models were divided into cervical spondylotic myelopath,cervical spondylotic radiculopathy,neck type cervical spondylosis,and other type cervical spondylosis.The advantages and disadvantages of various modeling methods were evaluated.Based on the studies of existing animal models,the molecular mechanism of cervical spondylosis was summarized.Therapeutic signals mediate nuclear factor-κB,phosphatidylinositol-3 kinase/protein kinase B,mitogen-activated protein kinase,and other pathways to regulate the biological processes of inflammation,apoptosis and autophagy of spinal cord,nerve root,intervertebral disc,muscle and other tissues,and ultimately delay the progression of cervical spondylosis.The quality of some studies is poor,and the clinical compatibility is not high.In the future,it is necessary to further standardize the animal model of cervical spondylosis,formulate relevant guidelines,improve the credibility of the research results,and lay a solid foundation for further human clinical trials.

Objective:To explore the results of four types of Urea cycle disorders (UCDs) in newborns from the Xuzhou region, assess the efficacy of newborn screening by tandem mass spectrometry (MS/MS), and analyze their genetic characteristics.Methods:A retrospective analysis was performed using tandem mass spectrometry to screen for inherited metabolic disorders in 691 712 newborns at the Maternal and Child Health Care Hospital of Xuzhou from November 2015 to December 2023. Ten children (cases 1-10) were diagnosed with Ornithine transcarbamylase deficiency (OTCD), Carbamoylphosphate synthase 1 deficiency (CPS1D), Arginase deficiency (ARGD), and Argininosuccinate synthase deficiency (ASSD) based on MS/MS and genetic testing. This study was approved by the Medical Ethics Committee of Xuzhou Maternity and Child Health Care Hospital (Ethics No.XZFY2024-051K-01J).Results:A total of 691 712 neonates were screened for UCDs using MS/MS, which identified 1 237, 1 237, 510, and 1 009 initial positive cases for OTCD, CPS1D, ASSD, and ARGD, respectively. After genetic testing, 1 case of OTCD, 1 case of CPS1D, 1 case of ASSD, and 7 cases of ARGD were confirmed. The overall positive predictive value for these four UCDs was 0.362%. Among the 10 diagnosed UCD cases, four novel variants were identified, which included OTC: c. 1024C>A (p.L342M) and ASS1: c. 826A>G (p.M276V), c.695C>T (p.P232L) and c. 694C>T (p.P232S). Bioinformatic analysis has rated these as variants of uncertain clinical significance or likely pathogenic based on guidelines from the American College of Medical Genetics and Genomics (ACMG). Conclusion:The incidence of four UCDs in neonates from the Xuzhou area is relatively low, and there is a correlation between genetic variants and clinical phenotypes. For novel variants with uncertain clinical significance or suspected pathogenicity, their pathogenicity should be clarified in conjunction with clinical and biochemical indicators. The four novel pathogenic variants of UCDs identified in this study have enriched the mutational spectrum of UCDs-associated genes in the Xuzhou region.

Critical care medicine-related treatment is an interdisciplinary and multi-professional process,often leading to secondary or concomitant mental disorders in clinical practice.Currently,there is no consensus on the pharmacological treatment of related mental illnesses in China.The Chinese Society of Psychosomatic Medicine collaborated with the Critical Care Medicine expert group to form a consensus writing expert group.After a systematic review of relevant literature,summarizing published domestic and foreign literature,and extensive discussions,the consensus was developed.The consensus elaborates on the principles and processes of the standardized use of psychotropic drugs in critical care medicine,as well as the clinical indications,precautions,and specific drug selection of various psychiatric medications,providing feasible suggestions and guidance for the clinical application of psychiatric medications in the intensive care unit.

Humans ; Aripiprazole/therapeutic use* ; Schizophrenia/drug therapy* ; Antipsychotic Agents/therapeutic use* ; Risperidone ; China ; Treatment Outcome

【Objective】 To explore the action mechanism of vinpocetine in improving learning and memory disorders in depressive rats after modified electroconvulsive therapy (MECT). 【Methods】 The models of depressive rats were constructed by chronic unpredictable mild stress (CUMS) method. A total of 30 rats with depression were randomly divided into depression group, MECT group, and MECT+vinpocetine (10 mg/kg) group, with 10 in each group. A total of 10 untreated healthy rats were enrolled as control group. The learning and memory ability were tested by Morris water maze test and novel object recognition test. The depression state was evaluated by sugar preference test. The brain slices of the hippocampus were prepared for electrophysiological experiments. The density of dendritic spine was detected by Golgi staining. The expressions of endocannabinoids related genes [diacylglycerol lipase (DAGLα), monoacylglycerol lipase (MAGL), and endocannabinoid type-I receptor (CB1R)] were detected by qPCR and Western blotting. The lentivirus was injected to downregulate the expressions of CB1R and DAGLα in the hippocampus. After re-modeling and treatment, behavioral tests were performed. 【Results】 Compared with control group, sugar preference, spatial exploration time, relative discrimination index, long-term potentiation (LTP), density of dendritic spine, expressions of DAGLα and CB1R were decreased, while escape latency and MAGL were increased in depression group (P<0.05). Compared with depression group, sugar preference, escape latency, and MAGL were increased, while spatial exploration time, relative discrimination index, LTP, density of dendritic spine, expressions of DAGLα and CB1R were decreased in MECT group (P<0.05). Compared with depression group, sugar preference, spatial exploration time, relative discrimination index, LTP, density of dendritic spine, expressions of DAGLα and CB1R were increased, while escape latency and MAGL were decreased in MECT+vinpocetine group (P<0.05). Compared with MECT group, sugar preference, spatial exploration time, relative discrimination index, LTP, density of dendritic spine, expressions of DAGLα and CB1R were increased, while escape latency and MAGL were decreased in MECT+vinpocetine group (P<0.05). The down-regulation of DAGLα or CB1R by lentivirus could inhibit the improvement effect of vinpocetine on behavioral performance of depressive rats after MECT. 【Conclusion】 Vinpocetine can significantly improve learning and memory disorders in depressive rats after MECT, which may be related to regulating the expressions of endocannabinoid-related genes and enhancing synaptic plasticity.

Objective : To explore the effects of Blonanserin on hippocampal neurons damage and PI3K / AKT / GSK3 β signaling pathways in rats with MK-801 induced schizophrenia． Methods : The schizophrenia models were induced by one-time intraperitoneal injection of MK-801．A total of 48 SD rats were randomly divided into normal group，model group，Blonanserin group ( 1 mg / kg Blonanserin) and risperidone group (0. 54 mg / kg risperidone) ， with 12 cases in each group．The behaviors of rats were observed by stereotyped behavior assay，open field test and Morris water maze．The pathological damage of hippocampus was observed by HE staining，which was scored．The levels of serum glucose-lipid metabolism indexes were detected．The mRNA and proteins of phosphatidylinositol 3- kinase (PI3K) ，protein kinase B (AKT) and glycogen synthase kinase 3 β ( GSK3 β) in hippocampal tissues were detected by real-time fluorescent quantitative PCR and Western blot. Results : Compared with model group，scores of stereotyped behaviors，total distance in open field test，escape latency and score of pathological damage in hippo- campus decreased in Blonanserin group and risperidone group，while times of crossing platform original site，levels of PI3K，AKT and GSK3 β mRNA，and phosphorylation levels of PI3K，AKT and GSK3 increased (P ＜0. 05) . However，there was no significant difference in the above indexes between Blonanserin group and risperidone group．The differences in levels of fasting blood glucose ( FPG) ，glycosylated hemoglobin ( HbA1c) ，triglyceride (TG) ，total cholesterol (TC) ，high-density lipoprotein (HDL) and low-density lipoprotein (LDL) among normal group，model group and Blonanserin group was not statistically significant．However，levels of FPG，HbA1c，TG and TC in risperidone group were higher than those in the other three groups (P＜0. 05) ，and there was no signifi- cant change in HDL or LDL． Conclusion Blonanserin may protect schizophrenia rats from hippocampal neurons damage，improve cognitive function，learning and memory ability by activating PI3K / AKT / GSK3 β signaling path- ways.

Objective:To evaluate the efficacy and safety of Tyrosine Kinase Inhibitors (TKIs) combined with stereotactic body radiation therapy(SBRT) in the treatment of renal cell carcinoma (RCC) patients with bone metastasis.Methods:The clinical data of 80 RCC patients with bone metastasis in Sun Yat-sen University Cancer Center from April 2010 to April 2020 were analyzed retrospectively. Among them, 64 patients were medium or high risk according to the International Metastatic Renal Cell Carcinoma Database Consortium(IMDC) score. Twenty-four patients received TKI therapy alone(Group A), and the other 56 cases received TKIs combined with SBRT to bone metastastic lesions (Group B).Results:The median follow-up period was 20.7 months (4.8-115.6 months), 70 patients received second or third-line targeted drug therapy, and 4 patients in group A and 15 patients in group B received TKI plus immunotherapy. Fifty-four patients had symptoms of bone pain before radiotherapy, 46 patients were satisfied with the analgesic effect after SBRT treatment. Twelve patients got complete response (CR) after bone lesions, and 32 patients achieved partial response (PR). Forty patients died of disease progression during follow-up. The median OS was: 20.7 months vs not reached(Group A vs. Group B), and the 2-y OS and 5-y OS were 50% vs. 62%, and 19% vs. 56%, respectively ( P=0.006). There were only 2 patients (3.6%) had grade 3 SBRT related adverse events. Conclusions:SBRT combined with TKIs improved the quality of life and prolonged the overall survival of RCC patients with bone metastasis.