Schizophrenia is a chronic and debilitating mental disorder.Around 20%to 40%of patients do not respond well to normal antipsychotic medication,and are ultimately diagnosed with treatment-resistant schizophrenia(TRS),representing the most severe and challenging form of schizophrenia.Currently,clozapine is the standard treatment for TRS.Early identification and standardized treatment can be beneficial to patients with TRS by controlling acute-phase symptoms as soon as possible,reducing suicidal rate and improving their quality of life.Under the guidance of the Steering Committee,this consensus was formed after multiple discussions by 30 psychiatric experts and anonymous Delphi surveys including 17 consensus opinions on treatment-resistant schizophrenia,which cover risk factors and prevention,diagnosis and evaluation,standardized clozapine treatment and management of adverse reactions,treatment regimens for clozapine resistance and intolerance,and psychosocial intervention,etc.The consensus-making process also incorporated evidence-based medicine to help standardize and guide diagnosis and treatment for adults with TRS in China.

Objective To study the effect and possible mechanism of Siraitiae fructus Qingyan Formula(SQF)on acute pharyngitis(AP)rats induced by ammonia water.Methods The active ingredients and targets of SQF were obtained from TCMSP database,pharyngitis targets were acquired from disease databases such as DrugBank,and the common targets were identified through intersections.Constructing protein-protein interaction(PPI)networks to obtain key targets.GO and KEGG enrichment analysis were carried out,and the"active ingredients-targets-pathways"network was constructed.Discovery Studio 2019 was used for molecular docking of active ingredients.The acute pharyngitis model was induced by fixed point quantitative application of ammonia water.After Siraitiae fructus Qingyan oral thick paste(SQP)low-,medium-and high-dose(4,8,16 g/kg)administration,The body mass,general behavior and symptoms of the rats were monitored continuously,and the score of pharyngeal swelling was recorded;the pathological changes of pharyngeal were observed by HE staining.The classification and the count of inflammatory cells were determined.The expression of inflammatory factors(IL-6,IL-1β,PGE2)and PI3K-AKT signaling pathways in pharyngeal tissues were assessed by quantitative real-time polymerase chain reaction(qRT-PCR).Results A total of 35 active ingredients,223 action targets and 2549 pharyngitis related targets were obtained through network pharmacology,with 153 common targets in total.The key targets were protein kinase B(PKB or AKT).Pathways involved PI3K-AKT signaling pathway.Combined with key targets,it was speculated that PI3K-AKT is an important signaling pathway for the treatment of acute pharyngitis with SQF.Compared with the model group,the related symptoms of AP rats were alleviated after the treatment of SQP.The redness and swelling of pharynx were significantly improved(P<0.001).The hyperplasia of the upper mucosa of pharyngeal was alleviated or disappeared,infiltration of a small amount of inflammatory cells,and hypertrophy and hyperplasia of submucosa glandular cells were alleviated.The numbers of inflammatory cells in blood of rats significantly decreased(P<0.05).And the mRNA expression levels of IL-6,IL-1β and PGE2 in pharyngeal tissues were significantly decreased(P<0.05,P<0.01,P<0.001),while the mRNA expression levels of PI3K,AKT and mTOR mRNA were remarkably raised(P<0.05,P<0.01).Conclusion SQF has obvious improvement effect on AP rats,and its mechanism may be related to reducing inflammation level,improving pharyngeal mucosa hyperplasia,inflammatory cells infiltration,hypertrophy and hyperplasia of submucosal glandular cells,and regulating PI3K-AKT signaling pathway.

Objective To explore the effects of different concentrations of simvastatin on nerve regeneration after sciatic nerve injury.Methods Rats were randomly divided into the normal group,the control group,the low-dose group and the high-dose group,with 3 rats in each group.Except for the normal group,adult rat sciatic nerve crush injury models were established in the other groups.Rats in the normal group and the control group were orally administered with water,while those in the low-dose group and high-dose group were orally administered with 98%simvastatin at dosages of 4 mg/mL and 40 mg/mL,respectively.The sciatic nerve regeneration in rats was evaluated by sciatic function index(SFI),HE staining,luxol fast blue(LFB)staining and immunofluorescence staining,etc.Results The SFI of rats in the high-dose group 7 days and 14 days after surgery were higher than those in the control group(P<0.05);there was no significant difference in SFI of rats between the low-dose group and the control group 7 days and 14 days after surgery(P>0.05).HE staining and LFB staining results showed that compared with the control group,the number of neurons of rats in the high-dose group increased,the nerve fibers and myelin were clearer and denser,and the nerve function was significantly restored;while no significant improvement was observed in the sciatic nerve of rats in the low-dose group.The immunofluorescence staining results showed that compared with the control group,the immunofluorescence intensity in the high-dose group increased,while that in the low-dose group decreased,the differences were statistically significant(P<0.05).Conclusion High-dose simvastatin can promote peripheral nerve regeneration by regulating the expression of M2 macrophages.

Objective:To explore the early predictive value of the triglyceride-glucose (TyG) index and the controlling nutritional status (CONUT) score for severe acute pancreatitis (SAP).Methods:Clinical data from 1 050 hospitalized patients with acute pancreatitis (AP) at the General Hospital of Central Theater Command between January 2019 and December 2023 were retrospectively analyzed. Patients were categorized into mild acute pancreatitis (MAP) group ( n=606), moderately severe acute pancreatitis (MSAP) group ( n=320), and SAP group ( n=124) based on AP severity. General clinical data, laboratory parameters, modified computed tomography severity index (MCTSI), bedside index for severity in acute pancreatitis (BISAP), TyG index, and CONUT score were compared among the three groups. Spearman correlation analysis was used to evaluate the relationship between TyG index, CONUT score and AP severity. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for AP severity. Receiver operating characteristic curves (ROC) were plotted to calculate the area under the curve (AUC), sensitivity, and specificity for evaluating the predictive efficacy of TyG index, CONUT score, and their combination for SAP. Results:Significant differences on TyG index and CONUT score were observed among AP patients with varying severity (all P value <0.001). Spearman correlation analysis further revealed positive correlations of TyG index ( r=0.174), CONUT score ( r=0.306) with AP severity (both P<0.001). Multivariate logistic regression identified neutrophil count ( OR=1.076, 95% CI 1.027-1.125), MCTSI ( OR=2.565, 95% CI 2.250-2.921), BISAP ( OR=3.522, 95% CI 2.726-4.549), TyG index ( OR=1.859, 95% CI 1.276-2.707), and CONUT score ( OR=1.155, 95% CI 1.035-1.288) as independent risk factors for AP severity. The combined predictive model equation was: -7.342+0.76×TyG+0.439×CONUT. ROC analysis showed that the AUC values of the TyG index, CONUT score, and the combined index (TyG index+CONUT score) were 0.583 (95% CI 0.529-0.637), 0.701 (95% CI 0.652-0.75), and 0.755 (95% CI 0.710-0.801), with sensitivities of 0.706, 0.677, and 0.742, and specificities of 0.884, 0.629, and 0.657, respectively (all P value <0.05). Conclusions:TyG index and CONUT score are positively correlated with AP severity and may serve as reliable predictors for SAP. Their combination could enhance the predictive accuracy for AP.

Objective To study the effect and possible mechanism of Siraitiae fructus Qingyan Formula(SQF)on acute pharyngitis(AP)rats induced by ammonia water.Methods The active ingredients and targets of SQF were obtained from TCMSP database,pharyngitis targets were acquired from disease databases such as DrugBank,and the common targets were identified through intersections.Constructing protein-protein interaction(PPI)networks to obtain key targets.GO and KEGG enrichment analysis were carried out,and the"active ingredients-targets-pathways"network was constructed.Discovery Studio 2019 was used for molecular docking of active ingredients.The acute pharyngitis model was induced by fixed point quantitative application of ammonia water.After Siraitiae fructus Qingyan oral thick paste(SQP)low-,medium-and high-dose(4,8,16 g/kg)administration,The body mass,general behavior and symptoms of the rats were monitored continuously,and the score of pharyngeal swelling was recorded;the pathological changes of pharyngeal were observed by HE staining.The classification and the count of inflammatory cells were determined.The expression of inflammatory factors(IL-6,IL-1β,PGE2)and PI3K-AKT signaling pathways in pharyngeal tissues were assessed by quantitative real-time polymerase chain reaction(qRT-PCR).Results A total of 35 active ingredients,223 action targets and 2549 pharyngitis related targets were obtained through network pharmacology,with 153 common targets in total.The key targets were protein kinase B(PKB or AKT).Pathways involved PI3K-AKT signaling pathway.Combined with key targets,it was speculated that PI3K-AKT is an important signaling pathway for the treatment of acute pharyngitis with SQF.Compared with the model group,the related symptoms of AP rats were alleviated after the treatment of SQP.The redness and swelling of pharynx were significantly improved(P<0.001).The hyperplasia of the upper mucosa of pharyngeal was alleviated or disappeared,infiltration of a small amount of inflammatory cells,and hypertrophy and hyperplasia of submucosa glandular cells were alleviated.The numbers of inflammatory cells in blood of rats significantly decreased(P<0.05).And the mRNA expression levels of IL-6,IL-1β and PGE2 in pharyngeal tissues were significantly decreased(P<0.05,P<0.01,P<0.001),while the mRNA expression levels of PI3K,AKT and mTOR mRNA were remarkably raised(P<0.05,P<0.01).Conclusion SQF has obvious improvement effect on AP rats,and its mechanism may be related to reducing inflammation level,improving pharyngeal mucosa hyperplasia,inflammatory cells infiltration,hypertrophy and hyperplasia of submucosal glandular cells,and regulating PI3K-AKT signaling pathway.

Schizophrenia is a chronic and debilitating mental disorder.Around 20%to 40%of patients do not respond well to normal antipsychotic medication,and are ultimately diagnosed with treatment-resistant schizophrenia(TRS),representing the most severe and challenging form of schizophrenia.Currently,clozapine is the standard treatment for TRS.Early identification and standardized treatment can be beneficial to patients with TRS by controlling acute-phase symptoms as soon as possible,reducing suicidal rate and improving their quality of life.Under the guidance of the Steering Committee,this consensus was formed after multiple discussions by 30 psychiatric experts and anonymous Delphi surveys including 17 consensus opinions on treatment-resistant schizophrenia,which cover risk factors and prevention,diagnosis and evaluation,standardized clozapine treatment and management of adverse reactions,treatment regimens for clozapine resistance and intolerance,and psychosocial intervention,etc.The consensus-making process also incorporated evidence-based medicine to help standardize and guide diagnosis and treatment for adults with TRS in China.

Objective To explore the effects of different concentrations of simvastatin on nerve regeneration after sciatic nerve injury.Methods Rats were randomly divided into the normal group,the control group,the low-dose group and the high-dose group,with 3 rats in each group.Except for the normal group,adult rat sciatic nerve crush injury models were established in the other groups.Rats in the normal group and the control group were orally administered with water,while those in the low-dose group and high-dose group were orally administered with 98%simvastatin at dosages of 4 mg/mL and 40 mg/mL,respectively.The sciatic nerve regeneration in rats was evaluated by sciatic function index(SFI),HE staining,luxol fast blue(LFB)staining and immunofluorescence staining,etc.Results The SFI of rats in the high-dose group 7 days and 14 days after surgery were higher than those in the control group(P<0.05);there was no significant difference in SFI of rats between the low-dose group and the control group 7 days and 14 days after surgery(P>0.05).HE staining and LFB staining results showed that compared with the control group,the number of neurons of rats in the high-dose group increased,the nerve fibers and myelin were clearer and denser,and the nerve function was significantly restored;while no significant improvement was observed in the sciatic nerve of rats in the low-dose group.The immunofluorescence staining results showed that compared with the control group,the immunofluorescence intensity in the high-dose group increased,while that in the low-dose group decreased,the differences were statistically significant(P<0.05).Conclusion High-dose simvastatin can promote peripheral nerve regeneration by regulating the expression of M2 macrophages.

Objective:To explore the early predictive value of the triglyceride-glucose (TyG) index and the controlling nutritional status (CONUT) score for severe acute pancreatitis (SAP).Methods:Clinical data from 1 050 hospitalized patients with acute pancreatitis (AP) at the General Hospital of Central Theater Command between January 2019 and December 2023 were retrospectively analyzed. Patients were categorized into mild acute pancreatitis (MAP) group ( n=606), moderately severe acute pancreatitis (MSAP) group ( n=320), and SAP group ( n=124) based on AP severity. General clinical data, laboratory parameters, modified computed tomography severity index (MCTSI), bedside index for severity in acute pancreatitis (BISAP), TyG index, and CONUT score were compared among the three groups. Spearman correlation analysis was used to evaluate the relationship between TyG index, CONUT score and AP severity. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for AP severity. Receiver operating characteristic curves (ROC) were plotted to calculate the area under the curve (AUC), sensitivity, and specificity for evaluating the predictive efficacy of TyG index, CONUT score, and their combination for SAP. Results:Significant differences on TyG index and CONUT score were observed among AP patients with varying severity (all P value <0.001). Spearman correlation analysis further revealed positive correlations of TyG index ( r=0.174), CONUT score ( r=0.306) with AP severity (both P<0.001). Multivariate logistic regression identified neutrophil count ( OR=1.076, 95% CI 1.027-1.125), MCTSI ( OR=2.565, 95% CI 2.250-2.921), BISAP ( OR=3.522, 95% CI 2.726-4.549), TyG index ( OR=1.859, 95% CI 1.276-2.707), and CONUT score ( OR=1.155, 95% CI 1.035-1.288) as independent risk factors for AP severity. The combined predictive model equation was: -7.342+0.76×TyG+0.439×CONUT. ROC analysis showed that the AUC values of the TyG index, CONUT score, and the combined index (TyG index+CONUT score) were 0.583 (95% CI 0.529-0.637), 0.701 (95% CI 0.652-0.75), and 0.755 (95% CI 0.710-0.801), with sensitivities of 0.706, 0.677, and 0.742, and specificities of 0.884, 0.629, and 0.657, respectively (all P value <0.05). Conclusions:TyG index and CONUT score are positively correlated with AP severity and may serve as reliable predictors for SAP. Their combination could enhance the predictive accuracy for AP.

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.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors not only have good lipid-lowering effects, but also have pleiotropic effects such as improving cardiovascular outcomes, relieving anti-inflammation, relieving oxidative stress and improving vascular endothelium. In recent years, the continuous development of PCSK9 inhibitors provides new ideas for the treatment of cardiovascular diseases. This article reviewed the pleiotropic mechanisms of PCSK9 inhibitors, especially on vascular endothelial function.