Objective: The purpose of this study was to explore the capacity for energy production under conditions of increased energy demand in schizophrenia (SCZ) subjects compared to healthy controls. Methods: Twelve healthy controls (33.00±6.07 years) and 12 subjects diagnosed with SCZ or schizoaffective disorder (36.00±8.33 years) matched for age and sex, were recruited for this study. Hypoxic stress was induced during MR scans to elevate the energy demand on the subjects’ bioenergetic systems. Participants breathed air with a lower oxygen concentration (FiO2=13%), maintaining their SpO2 levels (86%) during the initial phase of the scan. 31Phosphorus MR spectroscopy was employed to examine metabolite levels, including phosphocreatine (PCr), β-adenosine triphosphate (ATP), and inorganic phosphate (Pi), as well as the ratios of PCr/Pi and PCr/β-ATP, in regions such as the prefrontal cortex (PFC), anterior cingulate cortex (ACC), and posterior cortex (POC), as well as across the entire brain, during both hypoxia and hyperoxia scans. Results: Subjects with SCZ had significantly lower levels of Pi across the brain and particularly, in the PFC, POC, and ACC during the hypoxia scan. Moreover, levels of PCr/Pi, indicative of mitochondrial energy production, were found to be higher in the same brain regions in the SCZ group. No significant differences were found in hyperoxia scan phase. Conclusion These findings suggest a deficit in the bioenergetic systems of individuals with SCZ under conditions of heightened energy demand. Further studies are warranted.

ObjectiveTo construct a large language model （LLM）-based intelligent pre-consultation system for traditional Chinese medicine （TCM） to improve efficacy of clinical practice. MethodsA TCM large language model was fine-tuned using DeepSpeed ZeRO-3 distributed training strategy based on YAYI 2-30B. A weighted undirected graph network was designed and an agent-based syndrome differentiation model was established based on relationship data extracted from TCM literature and clinical records. An agent collaboration framework was developed to integrate the TCM LLM with the syndrome differentiation model. Model performance was comprehensively evaluated by Loss function， BLEU-4， and ROUGE-L metrics， through which training convergence， text generation quality， and language understanding capability were assessed. Professional knowledge test sets were developed to evaluate system proficiency in TCM physician licensure content， TCM pharmacist licensure content， TCM symptom terminology recognition， and meridian identification. Clinical tests were conducted to compare the system with attending physicians in terms of diagnostic accuracy， consultation rounds， and consultation duration. ResultsAfter 100 000 iterations， the training loss value was gradually stabilized at about 0.7±0.08， indicating that the TCM-LLM has been trained and has good generalization ability. The TCM-LLM scored 0.38 in BLEU-4 and 0.62 in ROUGE-L， suggesting that its natural language processing ability meets the standard. We obtained 2715 symptom terms， 505 relationships between diseases and syndromes， 1011 relationships between diseases and main symptoms， and 1 303 600 relationships among different symptoms， and constructed the Agent of syndrome differentiation model. The accuracy rates in the simulated tests for TCM practitioners， licensed pharmacists of Chinese materia medica， recognition of TCM symptom terminology， and meridian recognition were 94.09%， 78.00%， 87.50%， and 68.80%， respectively. In clinical tests， the syndrome differentiation accuracy of the system reached 88.33%， with fewer consultation rounds and shorter consultation time compared to the attending physicians （P＜0.01）， suggesting that the system has a certain pre- consultation ability. ConclusionThe LLM-based intelligent TCM pre-diagnosis system could simulate diagnostic thinking of TCM physicians to a certain extent. After understanding the patients' natural language， it collects all the patient's symptom through guided questioning， thereby enhancing the diagnostic and treatment efficiency of physicians as well as the consultation experience of the patients.

Objective: The purpose of this study was to explore the capacity for energy production under conditions of increased energy demand in schizophrenia (SCZ) subjects compared to healthy controls. Methods: Twelve healthy controls (33.00±6.07 years) and 12 subjects diagnosed with SCZ or schizoaffective disorder (36.00±8.33 years) matched for age and sex, were recruited for this study. Hypoxic stress was induced during MR scans to elevate the energy demand on the subjects’ bioenergetic systems. Participants breathed air with a lower oxygen concentration (FiO2=13%), maintaining their SpO2 levels (86%) during the initial phase of the scan. 31Phosphorus MR spectroscopy was employed to examine metabolite levels, including phosphocreatine (PCr), β-adenosine triphosphate (ATP), and inorganic phosphate (Pi), as well as the ratios of PCr/Pi and PCr/β-ATP, in regions such as the prefrontal cortex (PFC), anterior cingulate cortex (ACC), and posterior cortex (POC), as well as across the entire brain, during both hypoxia and hyperoxia scans. Results: Subjects with SCZ had significantly lower levels of Pi across the brain and particularly, in the PFC, POC, and ACC during the hypoxia scan. Moreover, levels of PCr/Pi, indicative of mitochondrial energy production, were found to be higher in the same brain regions in the SCZ group. No significant differences were found in hyperoxia scan phase. Conclusion These findings suggest a deficit in the bioenergetic systems of individuals with SCZ under conditions of heightened energy demand. Further studies are warranted.

Objective: The purpose of this study was to explore the capacity for energy production under conditions of increased energy demand in schizophrenia (SCZ) subjects compared to healthy controls. Methods: Twelve healthy controls (33.00±6.07 years) and 12 subjects diagnosed with SCZ or schizoaffective disorder (36.00±8.33 years) matched for age and sex, were recruited for this study. Hypoxic stress was induced during MR scans to elevate the energy demand on the subjects’ bioenergetic systems. Participants breathed air with a lower oxygen concentration (FiO2=13%), maintaining their SpO2 levels (86%) during the initial phase of the scan. 31Phosphorus MR spectroscopy was employed to examine metabolite levels, including phosphocreatine (PCr), β-adenosine triphosphate (ATP), and inorganic phosphate (Pi), as well as the ratios of PCr/Pi and PCr/β-ATP, in regions such as the prefrontal cortex (PFC), anterior cingulate cortex (ACC), and posterior cortex (POC), as well as across the entire brain, during both hypoxia and hyperoxia scans. Results: Subjects with SCZ had significantly lower levels of Pi across the brain and particularly, in the PFC, POC, and ACC during the hypoxia scan. Moreover, levels of PCr/Pi, indicative of mitochondrial energy production, were found to be higher in the same brain regions in the SCZ group. No significant differences were found in hyperoxia scan phase. Conclusion These findings suggest a deficit in the bioenergetic systems of individuals with SCZ under conditions of heightened energy demand. Further studies are warranted.

Objective: The purpose of this study was to explore the capacity for energy production under conditions of increased energy demand in schizophrenia (SCZ) subjects compared to healthy controls. Methods: Twelve healthy controls (33.00±6.07 years) and 12 subjects diagnosed with SCZ or schizoaffective disorder (36.00±8.33 years) matched for age and sex, were recruited for this study. Hypoxic stress was induced during MR scans to elevate the energy demand on the subjects’ bioenergetic systems. Participants breathed air with a lower oxygen concentration (FiO2=13%), maintaining their SpO2 levels (86%) during the initial phase of the scan. 31Phosphorus MR spectroscopy was employed to examine metabolite levels, including phosphocreatine (PCr), β-adenosine triphosphate (ATP), and inorganic phosphate (Pi), as well as the ratios of PCr/Pi and PCr/β-ATP, in regions such as the prefrontal cortex (PFC), anterior cingulate cortex (ACC), and posterior cortex (POC), as well as across the entire brain, during both hypoxia and hyperoxia scans. Results: Subjects with SCZ had significantly lower levels of Pi across the brain and particularly, in the PFC, POC, and ACC during the hypoxia scan. Moreover, levels of PCr/Pi, indicative of mitochondrial energy production, were found to be higher in the same brain regions in the SCZ group. No significant differences were found in hyperoxia scan phase. Conclusion These findings suggest a deficit in the bioenergetic systems of individuals with SCZ under conditions of heightened energy demand. Further studies are warranted.

Objective: The purpose of this study was to explore the capacity for energy production under conditions of increased energy demand in schizophrenia (SCZ) subjects compared to healthy controls. Methods: Twelve healthy controls (33.00±6.07 years) and 12 subjects diagnosed with SCZ or schizoaffective disorder (36.00±8.33 years) matched for age and sex, were recruited for this study. Hypoxic stress was induced during MR scans to elevate the energy demand on the subjects’ bioenergetic systems. Participants breathed air with a lower oxygen concentration (FiO2=13%), maintaining their SpO2 levels (86%) during the initial phase of the scan. 31Phosphorus MR spectroscopy was employed to examine metabolite levels, including phosphocreatine (PCr), β-adenosine triphosphate (ATP), and inorganic phosphate (Pi), as well as the ratios of PCr/Pi and PCr/β-ATP, in regions such as the prefrontal cortex (PFC), anterior cingulate cortex (ACC), and posterior cortex (POC), as well as across the entire brain, during both hypoxia and hyperoxia scans. Results: Subjects with SCZ had significantly lower levels of Pi across the brain and particularly, in the PFC, POC, and ACC during the hypoxia scan. Moreover, levels of PCr/Pi, indicative of mitochondrial energy production, were found to be higher in the same brain regions in the SCZ group. No significant differences were found in hyperoxia scan phase. Conclusion These findings suggest a deficit in the bioenergetic systems of individuals with SCZ under conditions of heightened energy demand. Further studies are warranted.

OBJECTIVE: To study the in vitro and in vivo antitumor effects of the polysaccharide of Alocasia cucullata (PAC) and the underlying mechanism. METHODS: B16F10 and 4T1 cells were cultured with PAC of 40 µg/mL, and PAC was withdrawn after 40 days of administration. The cell viability was detected by cell counting kit-8. The expression of Bcl-2 and Caspase-3 proteins were detected by Western blot and the expressions of ERK1/2 mRNA were detected by quantitative real-time polymerase chain reaction (qRT-PCR). A mouse melanoma model was established to study the effect of PAC during long-time administration. Mice were divided into 3 treatment groups: control group treated with saline water, positive control group (LNT group) treated with lentinan at 100 mg/(kg·d), and PAC group treated with PAC at 120 mg/(kg·d). The pathological changes of tumor tissues were observed by hematoxylin-eosin staining. The apoptosis of tumor tissues was detected by TUNEL staining. Bcl-2 and Caspase-3 protein expressions were detected by immunohistochemistry, and the expressions of ERK1/2, JNK1 and p38 mRNA were detected by qRT-PCR. RESULTS: In vitro, no strong inhibitory effects of PAC were found in various tumor cells after 48 or 72 h of administration. Interestingly however, after 40 days of cultivation under PAC, an inhibitory effect on B16F10 cells was found. Correspondingly, the long-time administration of PAC led to downregulation of Bcl-2 protein (P<0.05), up-regulation of Caspase-3 protein (P<0.05) and ERK1 mRNA (P<0.05) in B16F10 cells. The above results were verified by in vivo experiments. In addition, viability of B16F10 cells under long-time administration culture in vitro decreased after drug withdrawal, and similar results were also observed in 4T1 cells. CONCLUSIONS Long-time administration of PAC can significantly inhibit viability and promote apoptosis of tumor cells, and had obvious antitumor effect in tumor-bearing mice.
Mice ; Animals ; Alocasia/metabolism* ; MAP Kinase Signaling System ; Caspase 3/metabolism* ; Apoptosis ; RNA, Messenger/metabolism*

The quality control of traditional Chinese medicine(TCM)is the core issue to ensure the modernization,industrialization and internationalization of TCM.Compared with other detection methods,electrochemical analysis method has many advantages such as high sensitivity,fast detection speed and low cost,making it an important means of quality control for TCM and having broad development prospects.This article reviewed the research progress of electrochemical methods in quality control of TCM in recent years,discussed the application of electrochemical fingerprinting technique in identification of TCM,and comprehensively summarized the application of electrochemical technology in analyzing effective components and harmful substances in TCM,including flavonoids,alkaloids,quinones,glycosides,heavy metals and pesticide residues.Finally,the development prospects of electrochemical methods in the field of quality control of TCM were discussed.

Objective To analyze the burden and changing trend of testicular cancer in China from 1990 to 2019.Methods Based on the 2019 Global Burden of Disease Database(GBD 2019),analyze the incidence,mortality,disability-adjusted life years(DALYs),years of life lost(YLLs),years lived with disability(YLDs)and their variation trend of testicular cancer in Chinese population from 1990 to 2019.Evaluating changes in age standardized rate(ASR)by calculating annual estimated percentage change(EAPC).According to the age grouping,analyze the age distribution characteristics of testicular cancer disease burden by age group.Results In 2019,the incident cases,deaths,age-standardized incidence rate,and age-standardized mortality rate of testicular cancer in China were 17.17×103,1.21×103,2.39/105,and 0.16/105,respectively.Compared to 1990,incident cases,deaths,and age-standardized incidence rate increased obviously in China,which was consistent with the global change trend,while the increase was higher than the global level.However,both Chinese and global age-standardized mortality rate showed a downward trend.From 1990 to 2019,DALYs,YLLs and YLDs of testicular cancer increased by 29.66%,9.83%and 720.91%respectively in China.The two age groups,0-15 years group and 30-35 years group,were with highest incidence of testicular cancer,while the highest disease burden of testicular cancer was 30-35 years.Conclusion From 1990 to 2019,the disease burden of testicular cancer in China showed an upward trend.Adolescents and young adults should be the priority population for screening and prevention due to their higher incidence and disease burden.

BACKGROUND:Whether activating transcription factor 7 interacting protein(Atf7ip)is involved in the regulation in osteogenic differentiation is still controversial,and studying its impact on osteogenic differentiation and its specific mechanisms is of great significance. OBJECTIVE:To investigate the effect of Atf7ip on bone morphogenetic protein 2 promoting osteogenic differentiation of mouse embryonic osteoblast precursor cells(MC3T3-E1). METHODS:MC3T3-E1 cells cultured in vitro were divided into three groups:normal group,interference group(NC-siRNA group,Atf7ip-siRNA group),and high expression group(CMV-VC group and CMV-Atf7ip group),and were transfected for 24 hours,and then treated with 200 ng/mL bone morphogenetic protein 2 for 0,12,24,and 48 hours,respectively.qRT-PCR was used to detect the mRNA expression levels of Atf7ip,alkaline phosphatase,osteocalcin,type I collagen α1 in the cells of each group.Western blot assay was used to detect the protein expression of osteogenic differentiation markers Sp7 and Runx2,and the expression of Atf7ip binding molecule SETDB1,histone H3 and H3K9me3.Alkaline phosphatase activity was detected by alkaline phosphatase staining. RESULTS AND CONCLUSION:(1)With the increase of bone morphogenetic protein 2 treatment time,the protein and mRNA expression of Atf7ip decreased,while the protein expression of Sp7,Runx2 and the mRNA expression of osteocalcin and alkaline phosphatase increased significantly(P<0.05).There was no significant change in the protein expression of Atf7ip binding molecule SETDB1.(2)Compared with the NC-siRNA group,the protein expression of Sp7,Runx2 and the mRNA expression of osteocalcin and type I collagen α1 were significantly up-regulated(P<0.05),and alkaline phosphatase activity was significantly enhanced;and H3K9 methylation significantly decreased in the Atf7ip-siRNA group(P<0.05).(3)Compared with the CMV-VC group,the protein expression of Sp7 and Runx,as well as mRNA expression of osteocalcin,alkaline phosphatase,and type I collagen α1 was significantly downregulated(P<0.05),and the alkaline phosphatase activity was significantly reduced in the CMV-Atf7ip group,while the H3K9 methylation protein in the CMV-Atf7ip group was significantly upregulated compared to the control group(P<0.05).(4)In conclusion,Atf7ip expression was decreased during bone morphogenetic protein 2-induced osteogenic differentiation of MC3T3-E1,and osteogenic differentiation was significantly increased after knockdown of Atf7ip.Overexpression of Atf7ip significantly weakened osteogenic differentiation,indicating that Atf7ip is a negative regulatory factor of bone morphogenetic protein 2 promoting osteogenic differentiation of MC3T3-E1 cells.