BACKGROUND:Bone marrow mesenchymal stem cells are the main effector cells for bone formation.With the increase of age,the regenerative ability of bone marrow mesenchymal stem cells is weakened and the differentiation function is impaired,leading to poor osteoporosis.Therefore,restoring the regenerative capacity and cellular function of aged bone marrow mesenchymal stem cells is essential for the effective treatment of osteoporosis.OBJECTIVE:To investigate the effects of passage 3 and passage 11 bone marrow mesenchymal stem cells-derived exosomes of young rats on the aging of bone marrow mesenchymal stem cells derived from elderly rats.METHODS:Bone marrow mesenchymal stem cells from 6-8-week-old female SD rats were isolated and cultured,and passaged to the passages 3 and 11,respectively.Then,exosomes from passages 3 and 11 bone marrow mesenchymal stem cells were extracted.Bone marrow mesenchymal stem cells from 18-month-old female SD rats were isolated and cultured,passaged to passage 3,and divided into 3 groups.The control group was routinely cultured,and the other two groups were intervened with exosomes from passages 3 and 11 bone marrow mesenchymal stem cells.After 48 hours of exosome intervention,the expression of β-galactosidase in the nucleus was detected by β-galactosidase staining kit.The expression of aging-related genes was detected by qRT-PCR.The expression differences of miRNA in exosomes from passages 3 and 11 bone marrow mesenchymal stem cells were compared by Small RNA sequencing.RESULTS AND CONCLUSION:(1)Compared with the control group and passage 11 bone marrow mesenchymal stem cell-derived exosomes group,theβ-galactosidase activity of bone marrow mesenchymal stem cells of aged rats was significantly lower in the passage 3 bone marrow mesenchymal stem cell-derived exosomes group.(2)Compared with the control group,the expression of aging-related genes p21 and p16 was significantly reduced in the passage 3 bone marrow mesenchymal stem cell-derived exosome group(P＜0.05),while there was no significant difference in the expression of aging-related genes p21 and p16 in the passage 11 bone marrow mesenchymal stem cell-derived exosome group.(3)Sequencing results showed that there was a significant difference in the expression of miRNAs in the two exosomes,among which the miRNAs with the most significant expression differences were let-7c-5p,let-7b-5p,miR-320-3p,and miR-26a-5p.KEGG analysis results showed that significantly different miRNA enrichment pathways include mTOR,AMPK and other aging-related signaling pathways.The above results indicate that passage 3 bone marrow mesenchymal stem cell-derived exosomes have the ability to reverse the aging of bone marrow mesenchymal stem cells in aged rats.

BACKGROUND:Bone marrow mesenchymal stem cells are the main effector cells for bone formation.With the increase of age,the regenerative ability of bone marrow mesenchymal stem cells is weakened and the differentiation function is impaired,leading to poor osteoporosis.Therefore,restoring the regenerative capacity and cellular function of aged bone marrow mesenchymal stem cells is essential for the effective treatment of osteoporosis.OBJECTIVE:To investigate the effects of passage 3 and passage 11 bone marrow mesenchymal stem cells-derived exosomes of young rats on the aging of bone marrow mesenchymal stem cells derived from elderly rats.METHODS:Bone marrow mesenchymal stem cells from 6-8-week-old female SD rats were isolated and cultured,and passaged to the passages 3 and 11,respectively.Then,exosomes from passages 3 and 11 bone marrow mesenchymal stem cells were extracted.Bone marrow mesenchymal stem cells from 18-month-old female SD rats were isolated and cultured,passaged to passage 3,and divided into 3 groups.The control group was routinely cultured,and the other two groups were intervened with exosomes from passages 3 and 11 bone marrow mesenchymal stem cells.After 48 hours of exosome intervention,the expression of β-galactosidase in the nucleus was detected by β-galactosidase staining kit.The expression of aging-related genes was detected by qRT-PCR.The expression differences of miRNA in exosomes from passages 3 and 11 bone marrow mesenchymal stem cells were compared by Small RNA sequencing.RESULTS AND CONCLUSION:(1)Compared with the control group and passage 11 bone marrow mesenchymal stem cell-derived exosomes group,theβ-galactosidase activity of bone marrow mesenchymal stem cells of aged rats was significantly lower in the passage 3 bone marrow mesenchymal stem cell-derived exosomes group.(2)Compared with the control group,the expression of aging-related genes p21 and p16 was significantly reduced in the passage 3 bone marrow mesenchymal stem cell-derived exosome group(P＜0.05),while there was no significant difference in the expression of aging-related genes p21 and p16 in the passage 11 bone marrow mesenchymal stem cell-derived exosome group.(3)Sequencing results showed that there was a significant difference in the expression of miRNAs in the two exosomes,among which the miRNAs with the most significant expression differences were let-7c-5p,let-7b-5p,miR-320-3p,and miR-26a-5p.KEGG analysis results showed that significantly different miRNA enrichment pathways include mTOR,AMPK and other aging-related signaling pathways.The above results indicate that passage 3 bone marrow mesenchymal stem cell-derived exosomes have the ability to reverse the aging of bone marrow mesenchymal stem cells in aged rats.

To evaluate the efficacy,safety and acceptability of different drugs in the treatment of mixed states in bipolar disorder using the Cochrane systematic review method. The results showed that for the treatment of bipolar depression with mixed features,there is evidence to support the efficacy of lurasidone and quetiapine. Lurasidone has low metabolic and sedative side effects,and can be used in children and adolescents with bipolar depression with mixed features. Quetiapine has balanced anti-depressant and anti-manic effects,with low risk of phase transition. There is evidence to support the efficacy of olanzapine in the treatment of bipolar manic with mixed features. However,it is necessary to balance the efficacy and side effects of olanzapine,and pay attention to the risk of phase transition. For mixed episode in Bipolar disorder,aripiprazole had most research evidence. Aripiprazole has fewer side effects on metabolism and prolactin,and can be used in children with bipolar disorder. Valproate and lithium are recommended by experts for the treatment of mixed state in bipolar disorder. The inconsistency between current studies is still significant,and high-quality randomized controlled trials are urgently needed to provide more comprehensive evidence-based support for the treatment of mixed states in bipolar disorder.

Objective To report and analyze the clinical characteristics of kidney transplant recipients(KTRs)combined with novel coronavirus Omicron variant strain infection of novel coronavirus(SARS-CoV-2),and to investigate the possible factors affecting the serum creatinine change.Methods The patients under-going allogeneic kidney transplantation and complicating Omicron variant strain infection in this hospital from October 2022 to December 2023 were retrospectively observed.Their clinical data,basic complications and prognosis,etc.were collected and analyzed.The possible factors affecting the serum creatinine change were an-alyzed.Results Among the 114 cases of KTRs combined with Omicron variant strain infection included in this study,there were 90 cases(78.9％)in the home management group(group A),18 cases(15.8％)in the non-intensive isolation ward group(group B)and 6 cases(5.3％)in the ICU group(group C).The most common symptoms were in turn fever(90.4％),fatigue(65.8％)and cough(61.4％),the clinical manifesta-tions were mainly upper respiratory tract infection symptoms.The overall mortality rate was 2.6％(3/114),moreover the dead patients all were in the group C.The number of basic comorbidities in the group C was higher than that in the group B and group A(P＜0.05).The patients were re-divided into 33 cases(28.9％)in the creatinine increase group(group D),71 cases(62.3％)in the creatinine unchange group(group E)and 10 cases(8.8％)in the creatinine decrease group(group F).The patients in the F group were the patients with mild and moderate Omicron variant strain infection in the group A,and a larger proportions of the pa-tients in the group D and group F discontinued or reduced the calcineurin inhibitor(CNI)type drugs than in the group E.Conclusion The hazard of Omicron variant strains to KTRs has been greatly reduced compared with previous other variant strains.Realizing the immune balance between anti-infection and anti-rejection is the effective measure for preventing renal function damage in KTRs.

Objective:This study aimed to explore whether there are abnormalities in the kynurenine pathway in patients with depression and suicidal ideation, and their dynamic relationship with clinical symptoms.Methods:According to the DSM-5 diagnostic criteria, a total of 68 patients with depression were prospectively enrolled, including 28 males and 40 females, aged( M ( Q1, Q3)) 22.0 (17.3, 47.8) years, who were the inpatients in the Division of Mood Disorders of Shanghai Mental Health Center from July 2019 to July 2022. The depressed patients were divided into groups with ( n=41) or without suicidal ideation ( n=27) based on whether they chose "weak" or "moderate to strong" suicidal ideation in questions 4 and 5 of the Beck Scale for Suicide Ideation (BSI). And 72 gender-matched healthy controls were also enrolled, including 29 males and 43 females, aged 25.5 (24.0, 36.8) years. Hamilton Depression Rating Scale-24 (HAMD 24), Hamilton Anxiety Rating Scale (HAMA), and BSI were used to evaluate the depression symptoms, anxiety symptoms, and suicidal ideation of depressed patients. All the participants received fasting venous blood collection to measure the levels of kynurenine metabolites in plasma. Among them, depressed patients with suicidal ideation were followed up, and the assessment s of depression symptoms, anxiety symptoms, and suicidal ideation, as well as kynurenine metabolites measurements, were repeated at the end of the 2nd and 4th weeks. Ultra-high performance liquid chromatography-triple quadrupole mass spectrometry was used to measure the levels of kynurenine metabolites in plasma. The hematological indicators were log-transformed, Z-score standardized, and false discovery rate correction was used for multiple comparisons of different metabolites. The relationship between baseline kynurenine metabolites and scale scores was analyzed. The relationship between kynurenine metabolites and scale scores during the follow-up process was analyzed by a linear mixed-effects model. Results:The peripheral picolinic acid (0.39±0.87 vs -0.23±1.09, t=3.89), 3-hydroxykynurenine/kynurenine (3-HK/KYN) (0.38±0.85 vs -0.09±1.01, t=2.98) and 3-HK (0.31±0.81 vs 0.14±1.04, t=2.78) of patients with depression were lower than those of healthy controls (both P<0.05). No statistically significant difference was found between patients with depression with or without suicidal ideation in kynurenine metabolites. In patients with depression and suicidal ideation, baseline HAMD 24 and HAMA scores were positively correlated with plasma 3-HK (HAMD 24: r=0.38; HAMA: r=0.39) and 3-HK/KYN (HAMD 24: r=0.34; HAMA: r=0.37) levels (all P<0.05). After adjusting for age and gender factors, a linear mixed-effects model was established for the follow-up scale scores, and kynurenine metabolite levels of this group of patients, and the results showed that the positive effect of HAMA score on 3-HK/KYN during follow-up was statistically significant ( B=0.04, t=2.46, P<0.05). Conclusion:There are abnormalities in the kynurenine pathway of tryptophan metabolism in patients with depression. 3-HK and 3-HK/KYN are related to the severity of depression and anxiety in patients with depression and suicidal ideation, among which 3-HK/KYN, representing the activity of kynurenine-3-monooxygenase, is dynamically associated with anxiety level.

To evaluate the efficacy,safety and acceptability of different drugs in the treatment of mixed states in bipolar disorder using the Cochrane systematic review method. The results showed that for the treatment of bipolar depression with mixed features,there is evidence to support the efficacy of lurasidone and quetiapine. Lurasidone has low metabolic and sedative side effects,and can be used in children and adolescents with bipolar depression with mixed features. Quetiapine has balanced anti-depressant and anti-manic effects,with low risk of phase transition. There is evidence to support the efficacy of olanzapine in the treatment of bipolar manic with mixed features. However,it is necessary to balance the efficacy and side effects of olanzapine,and pay attention to the risk of phase transition. For mixed episode in Bipolar disorder,aripiprazole had most research evidence. Aripiprazole has fewer side effects on metabolism and prolactin,and can be used in children with bipolar disorder. Valproate and lithium are recommended by experts for the treatment of mixed state in bipolar disorder. The inconsistency between current studies is still significant,and high-quality randomized controlled trials are urgently needed to provide more comprehensive evidence-based support for the treatment of mixed states in bipolar disorder.

Objective:This study aimed to explore whether there are abnormalities in the kynurenine pathway in patients with depression and suicidal ideation, and their dynamic relationship with clinical symptoms.Methods:According to the DSM-5 diagnostic criteria, a total of 68 patients with depression were prospectively enrolled, including 28 males and 40 females, aged( M ( Q1, Q3)) 22.0 (17.3, 47.8) years, who were the inpatients in the Division of Mood Disorders of Shanghai Mental Health Center from July 2019 to July 2022. The depressed patients were divided into groups with ( n=41) or without suicidal ideation ( n=27) based on whether they chose "weak" or "moderate to strong" suicidal ideation in questions 4 and 5 of the Beck Scale for Suicide Ideation (BSI). And 72 gender-matched healthy controls were also enrolled, including 29 males and 43 females, aged 25.5 (24.0, 36.8) years. Hamilton Depression Rating Scale-24 (HAMD 24), Hamilton Anxiety Rating Scale (HAMA), and BSI were used to evaluate the depression symptoms, anxiety symptoms, and suicidal ideation of depressed patients. All the participants received fasting venous blood collection to measure the levels of kynurenine metabolites in plasma. Among them, depressed patients with suicidal ideation were followed up, and the assessment s of depression symptoms, anxiety symptoms, and suicidal ideation, as well as kynurenine metabolites measurements, were repeated at the end of the 2nd and 4th weeks. Ultra-high performance liquid chromatography-triple quadrupole mass spectrometry was used to measure the levels of kynurenine metabolites in plasma. The hematological indicators were log-transformed, Z-score standardized, and false discovery rate correction was used for multiple comparisons of different metabolites. The relationship between baseline kynurenine metabolites and scale scores was analyzed. The relationship between kynurenine metabolites and scale scores during the follow-up process was analyzed by a linear mixed-effects model. Results:The peripheral picolinic acid (0.39±0.87 vs -0.23±1.09, t=3.89), 3-hydroxykynurenine/kynurenine (3-HK/KYN) (0.38±0.85 vs -0.09±1.01, t=2.98) and 3-HK (0.31±0.81 vs 0.14±1.04, t=2.78) of patients with depression were lower than those of healthy controls (both P<0.05). No statistically significant difference was found between patients with depression with or without suicidal ideation in kynurenine metabolites. In patients with depression and suicidal ideation, baseline HAMD 24 and HAMA scores were positively correlated with plasma 3-HK (HAMD 24: r=0.38; HAMA: r=0.39) and 3-HK/KYN (HAMD 24: r=0.34; HAMA: r=0.37) levels (all P<0.05). After adjusting for age and gender factors, a linear mixed-effects model was established for the follow-up scale scores, and kynurenine metabolite levels of this group of patients, and the results showed that the positive effect of HAMA score on 3-HK/KYN during follow-up was statistically significant ( B=0.04, t=2.46, P<0.05). Conclusion:There are abnormalities in the kynurenine pathway of tryptophan metabolism in patients with depression. 3-HK and 3-HK/KYN are related to the severity of depression and anxiety in patients with depression and suicidal ideation, among which 3-HK/KYN, representing the activity of kynurenine-3-monooxygenase, is dynamically associated with anxiety level.

The rapid development of technology in the information age has brought profound changes to healthcare. In particular, the close integration of artificial intelligence technology and medical services has demonstrated potential application value in disease diagnosis, treatment and clinical research.Psychiatry strives to keep pace with the times and of information technology. Artificial intelligence has made multi-faceted explorations in psychiatric clinical research. The process is not only full of opportunities and challenges, but also insightful dawn.Meanwhile, the application of information technology in psychiatric clinical research also has inevitable limitations.Psychiatric clinical research needs to pay attention to real data in the real world. On the basis of standardization and safety, it should be expected that artificial intelligence technology and real data in psychiatric clinical diagnosis and treatment should be combined to strengthen evidence-based studies, update clinical diagnosis and treatment guidelines, and promote a tool for translational application.From the perspective of scientific development, these tools will eventually help psychiatrists benefit the majority of patients with mental illness and promote the vigorous development of psychiatry.

The rapid development of technology in the information age has brought profound changes to healthcare. In particular, the close integration of artificial intelligence technology and medical services has demonstrated potential application value in disease diagnosis, treatment and clinical research.Psychiatry strives to keep pace with the times and of information technology. Artificial intelligence has made multi-faceted explorations in psychiatric clinical research. The process is not only full of opportunities and challenges, but also insightful dawn.Meanwhile, the application of information technology in psychiatric clinical research also has inevitable limitations.Psychiatric clinical research needs to pay attention to real data in the real world. On the basis of standardization and safety, it should be expected that artificial intelligence technology and real data in psychiatric clinical diagnosis and treatment should be combined to strengthen evidence-based studies, update clinical diagnosis and treatment guidelines, and promote a tool for translational application.From the perspective of scientific development, these tools will eventually help psychiatrists benefit the majority of patients with mental illness and promote the vigorous development of psychiatry.

Objective:To investigate the clinical characteristics of bipolar disorder patients who present with depressive symptoms at their first episode.Methods:A total of 1 600 bipolar disorder patients with the first episode of depression who participated in the clinical pathway survey of bipolar disorder were included in this study. Demographic data, clinical phenotype, and symptomatic characteristics when they presented with their first mania were described. One-way analysis of variance was applied to compare the clinical characteristics between patients who visited the general hospitals and the ones who visited the mental health centers, and chi-square test was applied to compare symptomatology of patients at the first hypomania/mania episode and their mania relapse.Results:The average time from the first depressive episode to the first hypomanic/manic episode was 3.63 years. It took an average of 1.83 years from the first hypomanic/manic episode to the diagnosis of bipolar mania, and only 45.4% (728 cases) were diagnosed as bipolar disorder when they presented with depression at their first episode; It was an average of 5.45 years from the first depressive episode to the diagnosis of bipolar disorder; There were statistically significant differences in the number of previous depressive episodes ( F=7.119, P=0.008) and the total number of previous episodes ( F=3.980, P=0.046) between bipolar disorder patients seen in the mental health centres and general hospitals. The top three symptoms of the first manic episode were mood elation (83%, 215 cases); increased activity (81.5%, 211 cases); increased speech (79.9%, 207 cases). Compared with recurrent manic episodes, patients at their first manic episode were more likely to report more gregarious (χ2=13.277, P<0.01), eloquent/humorous (χ2=10.665, P=0.001), and less likely to report excessive use of psychoactive substances (χ2=3.990, P=0.046). Conclusions:It takes a long time for the diagnosis of bipolar disorder who presents with the depressive mood in their first episode. The first manic episode is not easy to identify, and the patients treated in general hospitals have more frequent depressive episodes, while the first manic episode shows some different symptoms from the recurrent manic episodes.