OBJECTIVE: Benzylisoquinoline alkaloids (BIAs) have pharmacological functions and clinical use. BIAs are mainly distributed in plant species across the order Ranunculales and the genus Phellodendron from Sapindales. The BIA biosynthesis has been intensively investigated in Ranunculales species. However, the accumulation mechanism of BIAs in Phellodendron is largely unknown. The aim of this study is to unravel the biosynthetic pathways of BIAs in Phellodendron amurens. METHODS: The transcriptome and metabolome data from 18 different tissues of P. amurense were meticulously sequenced and subsequently subjected to a thorough analysis. Weighted gene co-expression network analysis (WGCNA), a powerful systems biology approach that facilitates the construction and subsequent analysis of co-expression networks, was utilized to identify candidate genes involved in BIAs biosynthesis. Following this, recombinant plasmids containing candidate genes were expressed in Escherichia coli, a widely used prokaryotic expression system. The purpose of this genetic engineering endeavor was to express the candidate genes within the bacteria, thereby enabling the assessment of the resultant enzyme activity. RESULTS: The synonymous substitutions per synonymous site for paralogs indicated that at least one whole genome duplication event has occurred. The potential BIA biosynthetic pathway of P. amurense was proposed, and two PR10/Bet v1 members, 14 CYP450s, and 33 methyltransferases were selected as related to BIA biosynthesis. One PR10/Bet v1 was identified as norcoclaurine synthase, which could catalyze dopamine and 4-hydroxyphenylacetaldehyde into (S)-norcoclaurine. CONCLUSION Our studies provide important insights into the biosynthesis and evolution of BIAs in non-Ranunculales species.

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 compare the effects of 5 prone ventilation positions in patients with acute respiratory distress syndrome (ARDS) with network Meta-analysis.Methods:The randomized controlled trials on various prone ventilation positions in patients with ARDS were retrieved from Cochrane Library, EMbase, CINAHL, PubMed, Web of Science, SinoMed, CNKI, Chinese Medical Association Guideline Database, Wanfang Data, China Biology Medicine disc, VIP Information and Chinese Clinical Trial Registry from their inception to December 31, 2023. Literature screening, quality assessment and data extraction were done following the inclusion and exclusion criteria. Network Meta-analysis of outcome indicators was done using Stata 18.0.Results:A total of 19 articles, covering 1 284 patients and 5 prone ventilation positions (0°, 10°, 30°, 25° and 45°) were included. Cochrane risk assessment results showed that 15 articles were grade B and 4 articles were grade C. In direct comparisons, heterogeneity was acceptable ( I2≤50% and P≥0.1). In network analysis, the global and local consistency test result showed good consistency ( P>0.05). Network Meta-analysis result showed that the incidences of pressure injury in patients with 10°, 25°, 30° and 45° prone ventilation were significantly lower than that in patients with 0° prone ventilation, the incidence of pressure injury in patients with 25° prone ventilation was significantly lower than that in patients with 10° prone ventilation, and there were statistical differences ( P<0.05); the oxygenation index in patients with 25° prone ventilation was significantly better than that in patients with 0°, 30° and 45° prone ventilation, and there was statistical difference ( P<0.05). Conclusions:The 25° prone ventilation can both effectively improve oxygenation and maximally reduce the incidence of pressure injury in patients with ARDS.

BACKGROUND:Existing studies have preliminarily summarized the potential association between muscle activity of the affected lower limb and gait stability during walking in patients undergoing anterior cruciate ligament reconstruction.However,there are some issues such as incomplete observation of muscle categories,incomplete observation of walking action phases,and failure to consider synergistic effects among multiple muscle groups,which urgently require further improvement in this study.OBJECTIVE:To monitor muscle synergy information of the affected leg during walking in patients undergoing anterior cruciate ligament reconstruction and to analyze the association between muscle synergy information and gait stability.METHODS:Twenty-four male patients aged(21.66±4.09)years undergoing anterior cruciate ligament reconstruction,were recruited.Electromyographic and center of pressure data were collected from the affected lower limb during walking.A non-negative matrix decomposition algorithm was used to extract the number of muscle synergic elements from the affected leg,the time spent in peak activation of each muscle synergic element,and the muscle relative weight indexes.Correlation analysis was then performed with the center of pressure indexes.RESULTS AND CONCLUSION:Six types of muscle synergies were identified in the affected leg.The number of muscle synergic elements showed no significant correlation with the distance and speed of lateral displacement of the center of pressure.Regarding the peak activation time of muscle synergic elements,synergic element 3 in the dominant gait loading response period showed a significant negative correlation with the lateral displacement distance of the center of pressure(r=-0.413,P=0.045)and a significant negative correlation with the lateral displacement velocity of the center of pressure(r=-0.470,P=0.020).The activation time of the remaining types of muscle synergic elements was not significantly related with patient's gait stability indices.In terms of muscle relative weights,the rectus femoris muscle of synergistic element 1 in the dominant gait loading response period showed a significant negative correlation with the lateral displacement distance of the center of pressure(r=-0.592,P=0.005)and a significant negative correlation with the lateral displacement speed of the center of pressure(r=-0.529,P=0.014).Additionally,the relative weight of the biceps femoris muscle of synergistic element 3 in the dominant gait loading response period showed a significant negative correlation with the lateral displacement distance of the center of pressure(r=-0.428,P=0.037).To conclude,the central system in patients undergoing anterior cruciate ligament reconstruction regulates the synergistic muscle activity of the affected leg during walking to enhance gait stability in two primary ways:by prolonging the activation time of the muscle synergists during the dominant loading response period and enhancing the activation of the quadriceps muscle,in order to enhance the control of eccentric contractions of the knee joint during the landing of the affected leg and improve the stability of the knee joint;and by increasing the activation of the biceps femoris muscle during the loading response period,which increases the degree of knee flexion and enhances the lower limb's cushioning function during the landing of the affected leg.

Objective:To study the development status and characteristics of the Traditional Chinese Medicine(TCM)service capacity of primary medical institutions(referred as primary)in Beijing.Methods:The case-base aggregation method was used to analyze the total amount,distribution,and development changes of total TCM costs in primary healthcare institutions in Beijing.Results:From 2019 to 2023,the average annual growth rate of the TCM costs of primary healthcare institutions in Beijing was 10.09％,and the proportion in total TCM costs increased from 16.01％to 18.19％.The average annual growth rate of the TCM costs of community health service centers(stations)was 11.78％,but there were negative growths in outpatient departments,clinics,and village clinics.The proportion of the primary TCM costs in its health costs increased from 29.16％to 32.56％.The average annual growth rate of income from primary herbal medicines and processed Chinese medicines were 16.75％and 10.13％.Conclusion:The primary TCM undertaking has developed steadily,and Beijing should continue to guide high-quality TCM resources to sink.Multiple measures should be taken to promote the development of TCM in outpatient departments,clinics,and village clinics.The coordination between prices and medical insurance reimbursement and payment methods should be strengthened.Supervision over the quality and use of Chinese medicine should be strengthened,and the technical service capabilities of primary TCM should be enhanced.

Mental disorders frequently co-occur with other physical illnesses,becoming one of the leading causes of disability worldwide.Early diagnosis and intervention are crucial for the effective management of these disorders.Currently,biomarker studies on mental disorders predominantly concentrate on genes,blood indicators,and imaging features of the brain.There is a growing interest in objective phenotypic markers as a research focus.It is established that the retina is part of the central nervous system(CNS),which extends from the mesencephalon and develops concurrently with the brain during the embryonic period.Given the overlapping pathophysiological mechanisms between neurodegenerative diseases and mental disorders,studying the structural and functional changes in the inner layers of the retina has emerged as a new direction in mental health research.The advent of optical coherence tomography(OCT)has enabled microscopic imaging of retinal structures.OCT is capable of objectively quantifying the retinal sub-layers and offers the advantages of being non-invasive,non-contact,and high-resolution.The use of OCT to explore structural changes in the retina among individuals with schizophrenia,bipolar disorder,major depression and other psychiatric disorders has been well documented;however,there is a paucity of reviews on this topic.This review summarizes current research on retinal structural alterations in patients with mental disorders,and the results demonstrate reduced thickness in certain sub-layers of the retina structure in patients with several mental disorders,which supports that the retina structure has the potential to be a biomarker for mental disorders and offers a novel avenue for research in the diagnosis and treatment.

ObjectiveTo clarify the anti-inflammatory and lung-protective effects of Yantiao prescription on lipopolysaccharide （LPS）-induced acute lung injury （ALI）， and to explore the impact of Yantiao prescription on the metabolic pathways of arachidonic acid （AA） in vivo. MethodsThirty male C57BL/6J mice were randomly divided into the following groups based on body weight： normal group， model group， dexamethasone group （2 mg·kg^-1）， low-dose Yantiao prescription group （18 g·kg^-1）， and high-dose Yantiao prescription group （36 g·kg^-1）， with 6 mice in each group. The ALI mouse model was established by intraperitoneal injection of LPS. The treatment groups received oral gavage once a day for 7 consecutive days， and serum and lung tissue were collected at the end of the experiment. The content of pro-inflammatory cytokines tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） in serum was detected by enzyme-linked immunosorbent assay （ELISA）. Hematoxylin-eosin （HE） staining was used to assess lung tissue pathology. The wet/dry weight ratio （W/D） and myeloperoxidase （MPO） activity in lung tissue were measured. The content of AA metabolites in serum and lung tissue was measured by liquid chromatography triple quadrupole-mass spectrometry （LC-MS/MS）. ResultsCompared with the conditions in the normal group， the content of serum pro-inflammatory cytokines TNF-α， IL-1β， and IL-6 in the model group was significantly increased （P<0.01）. The alveolar structure in mice was severely damaged， with markedly thickened alveolar walls and extensive inflammatory cell infiltration. The W/D ratio and MPO activity in lung tissue were significantly increased （P<0.01）. The content of AA metabolites， including prostaglandin D₂ （PGD₂）， prostaglandin E₂ （PGE₂）， 11（S）-hydroxy-eicosatetraenoic acid ［11（S）-HETE］， and 5-hydroxy-eicosatetraenoic acid （5-HETE） in serum and lung tissue was significantly increased （P<0.05）， while the content of 11，12-epoxyeicosatrienoic acid （11，12-EET） and 14，15-epoxyeicosatrienoic acid （14，15-EET） in serum was significantly decreased （P<0.01）. Compared with the results in the model group， the content of serum pro-inflammatory cytokines TNF-α， IL-1β， and IL-6 in the dexamethasone group， low-dose Yantiao prescription group， and high-dose Yantiao prescription group was significantly reduced （P<0.05）. Mild thickening of alveolar walls， scattered inflammatory cell infiltration， and relatively intact tissue structure with improved alveolar architecture were observed. The W/D ratio and MPO activity in lung tissue were significantly reduced （P<0.01）. The content of AA metabolites PGD₂， PGE₂， 11（S）-HETE， and 5-HETE in serum from the dexamethasone group was significantly decreased （P<0.05）， while the content of 14，15-EET in serum significantly increased （P<0.01）， and the content of 5-HETE in lung tissue significantly decreased （P<0.01）. In the low-dose and high-dose Yantiao prescription groups， the content of AA metabolites PGD₂， PGE₂， 11（S）-HETE， and 5-HETE in serum and lung tissue was significantly decreased （P<0.05）， while the content of 11，12-EET in both serum and lung tissue was significantly increased （P<0.05）. ConclusionYantiao prescription has significant protective effects against LPS-induced ALI， which are related to its regulation of AA metabolic pathways in vivo.

Objective: To investigate the trend in disease burden of interstitial lung disease (ILD) in China from 1990 to 2021, so as to provide a reference for formulating prevention and control strategies for chronic respiratory diseases. Methods: Based on the Global Burden of Disease 2021 database, data on the number of incident cases, incidence, standardized incidence, number of deaths, mortality, standardized mortality, number of disability-adjusted life years (DALY), DALY rate, and standardized DALY rate of ILD in China were collected. The incidence, mortality, and DALY rate were used to analyze the disease burden of ILD. The estimated annual percentage change (EAPC) was employed to assess the trend in standardized incidence, standardized mortality, and standardized DALY rate of ILD from 1990 to 2021. Rate decomposition analysis was applied to identify the main contributing factors affecting the trend in disease burden. Results: In 2021, China reported 48 514 cases, 7 674 deaths, and 222 288 person-years of DALY due to ILD, representing increases of 155.43%, 159.70%, and 97.34%, respectively, compared with 1990. From 1990 to 2021, the standardized incidence and standardized mortality of ILD in China showed upward trends (EAPC=1.106% and 0.239%, both P<0.05), while the standardized DALY rate showed a downward trend (EAPC=-0.230%, P<0.05). From 1990 to 2021, the standardized incidence and standardized mortality among males showed upward trends (EAPC=1.199% and 0.520%, both P<0.05), while the trend in the standardized DALY rate was not statistically significant (P>0.05). Among females, the standardized incidence of ILD showed an upward trend (EAPC=0.966%, P<0.05), while the standardized mortality and standardized DALY rate showed downward trends (EAPC=-0.306% and -0.760%, both P<0.05). In 2021, the incidence, mortality, and DALY rate of ILD in China increased with age, peaking in the group aged ≥95 years at 14.84/105, 13.90/105, and 124.71/105, respectively. Across all age groups aged ≥55 years, the incidence, mortality, and DALY rate of ILD were consistently higher in males than in females. The increase in the number of incident cases, deaths, and DALY due to ILD in China from 1990 to 2021 was primarily influenced by population aging, with contribution rates of 42.65%, 68.25%, and 69.79%, respectively. Conclusions From 1990 to 2021, the incidence and mortality risk of ILD in China showed upward trends, while the disability risk demonstrated a downward trend. Males bore a heavier disease burden of ILD, and aging was identified as the primary factor contributing to the increased burden of ILD in China.

Objective:To detect the expression level and clinical significance of centromere protein I (CENPI) in hepatocellular carcinoma (HCC) and to preliminarily explore the effects of CENPI on the biological behavior of liver cancer cells and its possible molecular mechanisms. Methods:The TCGA database, real-time fluorescent quantitative polymerase chain reaction, Western blot, and immunohistochemical staining experiments were used to analyze and detect the expression differences of CENPI in liver cancer and adjacent tissues. The correlation between CENPI expression levels and clinical pathological features were analyzed in combination with clinical data from HCC patients. The value of CENPI in the diagnosis and prognosis assessment of HCC was explored by plotting receiver operating characteristic curves and Kaplan-Meier survival curves. Furthermore, we investigated the impact of CENPI overexpression on the migration and healing capabilities of liver cancer cells using Transwell and wound healing experiments. Finally, the effects of CENPI on the epithelial-mesenchymal transition process in liver cancer cells and the potential molecular mechanisms were explored using Western blot. Comparisons between two groups were analyzed using t-tests, and comparisons among multiple groups were analyzed using one-way ANOVA. The expression of CENPI and its correlation with clinical pathological features were analyzed using the χ2 test. Results:The TCGA database analysis showed that the expression level of CENPI was significantly higher in liver cancer tissues than adjacent tissues, which was further validated by real-time fluorescent quantitative polymerase chain reaction, Western blotting, and immunohistochemical staining experiments. Combined clinical data analysis from HCC patients demonstrated that high expression of CENPI was positively correlated with the degree of tumor malignancy, T stage, and disease prognosis. The Kaplan-Meier survival curve indicated that the 5-year survival rate was significantly lower in patients with high CENPI expression compared to those with low expression. The results of the receiver operating characteristic curve further indicated that the expression level of CENPI had accurately predicted the prognosis of liver cancer patients (area under the curve=0.962). Transwell and wound healing experiment results indicated that overexpressing CENPI in Hep3B and Huh7 cells significantly increased cell migration numbers and healing rates. Further research results showed that overexpressing CENPI significantly upregulated the expression of mesenchymal cell-related marker genes: N-cadherin, Vimentin, and Snail protein, while the expression of the epithelial cell-related marker gene E-cadherin was significantly reduced. The mechanistic study revealed that when CENPI was overexpressed, the MEK and ERK phosphorylation levels and the expression of RAS protein were significantly increased compared to the control group, and the difference was statistically significant. Conclusion:The high expression of CENPI in the tissues of HCC patients is associated with poor prognosis, potentially promoting the migration of liver cancer cells and the epithelial-mesenchymal transition process by activating the RAS/MEK/ERK signaling pathway axis, suggesting that the CENPI gene may be a promising target for HCC treatment.

Non-alcoholic fatty liver disease(NAFLD)is a chronic liver disease caused by excessive lipid accumulation in the liver.Its incidence rate is increasing year by year and has become an increasingly serious public healthy problem.The pathogenesis of NAFLD is complex and has not been fully clarified at present.It is mainly related to multiple factors such as genetics,metabolism,intestinal flora and immune response.In order to explore the medication rules and mechanism of action of traditional Chinese medicine(TCM)in the treatment of NAFLD,and to provide references for the treatment of NAFLD with TCM and the research and development of new drugs,this article summarizes the TCM pathogenesis of NAFLD(such as"phlegm and blood stasis interlacing","liver depression and spleen deficiency",etc.)and modern etiology and pathogenesis(such as insulin resistance,lipid disorder,mitochondrial dysfunction,oxidative stress,etc.).The clinical research and experimental data at home and abroad in recent years were integrated to analyze the pathological process of NAFLD intervention by TCM through multiple targets,including improving insulin resistance and lipid metabolism disorders,inhibiting oxidative stress and mitochondrial dysfunction,etc.TCM has shown unique advantages in the prevention and treatment of NAFLD.However,the depth of its mechanism analysis and the level of clinical research still need to be improved.In the future,it is necessary to deepen the mechanism research by combining multi-omics technology to accelerate the modernization development of TCM.