Research progress of IDO1-mediated tryptophan metabolism in sepsis / 药学学报

Sepsis is a condition characterized by organ dysfunction resulting from the systemic inflammatory response triggered by an infection. Excessive inflammation and immunosuppression are intertwined, and severe cases may even develop into multiple organ failure. Studies have shown that indoleamine 2,3-dioxygenase 1-mediated tryptophan metabolism is involved in the occurrence and development of sepsis, and elevated plasma kynurenine levels and Kyn/Trp ratios are early indicators of sepsis development. In this paper, we provide a comprehensive summary of the role of IDO1 in the acute inflammatory phase of sepsis, late immunosuppression, and organ damage. This includes its regulation of inflammatory state, immune cell function, blood pressure, and other aspects. Additionally, we analyze preclinical studies on targeted IDO1 drugs. An in-depth understanding and study of IDO may help to understand the pathogenesis and clinical significance of sepsis and multiple organ damage from a new perspective and provide new research ideas for exploring its prevention and treatment methods.

Pathological Mechanism of Diabetes Based on NF-κB Signaling Pathway and Traditional Chinese Medicine Intervention： A Review / 中国实验方剂学杂志

As people's living standards improve， the development trend of diabetes has gradually become severe. Diabetes is a chronic inflammatory disease associated with abnormal expression of nuclear factor-kappa B （NF-κB） in patients. NF-κB exists in various tissue cells and participates in the regulation of a variety of genes related to immune function and inflammation. Varieties of factors can activate NF-κB when the body is stimulated by external factors， so as to produce inflammation and other reactions. Previous studies on NF-κB mainly focus on cancer， and the pathological mechanism of the treatment of diabetes by related signaling pathways and the progress of traditional Chinese medicine （TCM） treatment have not been systematically elaborated on. By referring to the relevant literature in China and abroad， it was found that NF-κB is not isolated in the development and progression of diabetes but is associated with signal molecules related to inflammation， oxidative stress， and energy metabolism， and it is involved in mediating inflammation， pancreatic β cell apoptosis， insulin signal transduction， and other physiological functions. Therefore， blocking the transmission of NF-κB signaling pathway is beneficial to the treatment of diabetes. At present， Western medicine for the treatment of diabetes mainly includes oral hypoglycemic drugs and insulin injections， but the adverse reactions are obvious. TCM has been characterized by multi-target， extensive action， and excellent curative effects in the treatment of diabetes. TCM and its compounds with functions of tonifying Qi and promoting blood circulation， regulating qi and eliminating phlegm， clearing heat and detoxifying， and nourishing Yin and moistening dryness can effectively intervene in the abnormal expression of NF-κB signaling pathway in vivo through anti-inflammatory effects. In this paper， the association between NF-κB signaling pathway and diabetes was summarized， and the modern research progress of TCM intervention of NF-κB signaling pathway in the treatment of diabetes in the past five years was reviewed， so as to lay a laboratory foundation for the study of a new pathological mechanism of diabetes based on NF-κB signaling pathway and provide new targets and research direction for the prevention and treatment of diabetes and development of related TCM.

Ancient Literature Analysis and Modern Clinical Application of Famous Classical Formula Huagaisan / 中国实验方剂学杂志

ObjectiveTo sort out the historical evolution， prescription evolution and modern clinical application of Huagaisan. MethodHuagaisan and its synonym Huagaitang are used as keywords to search the databases of Traditional Chinese Medicine Think Tank， Chinese Medical Dictionary， Airusheng Chinese Medical Database and China National Knowledge Infrastructure（CNKI）. According to the inclusion and exclusion criteria， we obtained the information of ancient books and modern clinical research literature related to Huagaisan， and systematically reviewed and analyzed the historical origin， prescription composition， preparation method， dosage， efficacy， medicinal material origin， processing method and modern clinical application of Huagaisan. ResultA total of 198 pieces of ancient book information were included， involving 93 ancient Chinese medicine books. Huagaisan was composed of fried Perillae Fructus， red Poria， fried Mori Cortex， Citri Eoxcarpium Rubrum， stir-fried Armeniacae Semen Amarum， Ephedrae Herba and fried Glycyrrhizae Radix et Rhizoma， which had the efficacy of promoting the lungs and relieving epidemiological symptoms， expelling phlegm and relieving cough， and treating cough with wind-cold bundled epidemiological symptoms and stagnation of phlegm and Qi. The preparation method was suggested as boiling powder， crushing the seven herbs into coarse particles， the dosage of each drug was fried Perillae Fructus of 1.27 g， red Poria of 1.27 g， fried Mori Cortex of 1.27 g， Citri Eoxcarpium Rubrum of 1.27 g， stir-fried Armeniacae Semen Amarum of 1.27 g， Ephedrae Herba of 1.27 g and fried Glycyrrhizae Radix et Rhizoma of 0.64 g， taking 8.26 g when decocting， adding 300 mL of water， decocting to 210 mL， removing the dregs， and taking it warmly after meals. Twenty-one clinical research papers were included to analyze the modern clinical application of Huagaisan， which was mainly used in the treatment of respiratory diseases such as pneumonia， asthma， bronchitis and so on. ConclusionThis paper has verified and summarized the key information of the famous classical formula Huagaisan， which can provide a detailed reference basis for the development and clinical application of its compound preparation.

Aerobic activity reducing depression in school-age children: a multiple mediation effects analysis based on five dimensions of psychosocial functioning / 中国康复理论与实践

ObjectiveTo explore the mechanism of aerobic capacity on depression in school-age children, and the multiple mediators of the five dimensions of psychosocial functioning (emotional symptoms, conduct problems, peer problems, prosocial behavior and hyperactivity) between aerobic capacity and depression. MethodsFrom October to December, 2021, pupils of Grade two to Grade five from two primary schools were chester-sampled and investigated using 20-meter multistage shuttle run test, Depression Self-Rating Scale for Children, Self-reported Strengths and Difficulties Questionnaire. ResultsA total of 391 pupils underwent 20-meter multistage shuttle run test, and 312 out of them answering the questionnaires, and 294 questionnaires were valid. Aerobic capacity, depression, emotional symptoms, peer problems, prosocial behavior and hyperactivity were significantly correlated with each other (|r| > 0.127, P < 0.05) (except aerobic capacity and peer problems, and emotional symptoms and prosocial behavior). The results of the multiple mediation effect model showed that aerobic capacity could directly and negatively predict depression, and the mediating effects of emotional symptoms, peer problems, prosocial behavior and hyperactivity were significant, accounting for 34.37%, 12.54%, 34.06% and 17.80% of the total mediating effect, respectively. ConclusionThe aerobic capacity could not only directly affect depression of school-age children, but also improve their psychosocial functioning by reducing emotional symptoms, peer problems and hyperactivity, and increasing prosocial behavior, to indirectly affect their depression.

Application progress of electronic tongue on taste evaluation for drug products / 药学学报

The taste of oral dosage forms has become a critical factor affecting the drug compliance and adherence to the treatment, and clinical application of the drug product may seriously restricted due to its bad taste. On the basis of the statement for the basic principle and specific performance of existing instruments, the application progress of electronic tongue on drug taste evaluation is addressed in detail. In view of its objective, fatigue-free, less harmful and accurate advantages, electronic tongue has been widely and meaningfully applied in the aspects of bitterness masking, and quality assessment and assurance of drug products. In addition, the reasons limiting the popularization of electronic tongue are mentioned in the paper, and some suggestions might be useful to enlarge the further application in the future.

Study of government responsibility on village clinics construction / 中华医院管理杂志

As the " bottom" of the rural three-level medical and health network, the village clinic is the closest medical and health institution to the villagers. Through field research on H District of Beijing, the author found that the government implemented the management responsibility of village clinics by issuing health policies to carry out the standardization construction, strengthened the practice management of village doctors, and stabilized the income source of rural doctors, so that village doctors could better assume the functions of village level public health and prevention and treatment of common diseases. However, the unclear ownership relationship of village clinics and the labor relationship of village doctors, the differences in hardware configuration and the convergence of post responsibilities under different management systems affected the government′s implementation of the management responsibility of village clinics. Therefore, it could be necessary to pay attention to the change of policy environment, timely reform and mechanism integration of village clinics, and establish a career development mechanism connecting counties and villages. The bottleneck in the construction of village clinics will be broken, and the goal of " quality medical and health services nearby" for rural residents will be realized.

Investigation on the demand and management status quo of scientific research assistants in hospitals and analysis of their development path based on the perspective of scientific research managers / 中华医学科研管理杂志

Objective:This study aims to explore the possible development path of hospital research assistants in China based on the cognition of the demand and management status quo from research management personnel in tertiary hospitals.Methods:62 scientific research management personnel from all over the country were surveyed, data about their cognition and the current status of scientific research assistants, that including the willingness of employ, position cognition, eligibility and competence, quantity and efficiency, management implementation, influencing factors and difficulties in team development, were collected and analyzed. Regarding to the practical needs and management status, the results were described by frequency, percentage and average score, and the rank sum test was used to verify whether there was any difference in the employment intention between the management department and the project team in the cognition of the survey subjects.Results:From the perspective of scientific research managers, there is a strong willingness at hospital level to employ the research assistant, positions require applicants with bachelor′s degree or above in medicine or other related majors. The most urgent needs are management of project funds, equipment and consumables, research integrity and ethics.The interviewees who work with research assistants think that the effect of research assistants on improving scientific research efficiency is obvious.However, the percentage of formulation of research assistants management measures is less than 40%, and the percentages of uniformly organized training and assessment are relatively low. There are still problems and challenges, such as incomplete cognition of the positioning and function, incomplete functional and vocational system, imperfect incentive mechanism and insufficient support for ability cultivation and improvement.Conclusions:It′s necessary to strengthen the top-down design of the development of scientific research assistant team and the construction of career system, improve the management basis and implementation mechanism, supporting resources should be in place, and promote capacity building system in order to develop a long-term mechanism of mutual promotion between the team building of scientific research assistants and the innovation of hospital scientific research management.

Repair of scalp defect with anterolateral thigh perforator flap after revascularisation of moyamoya disease: a report of 7 cases / 中华显微外科杂志

Objective:To investigate the clinical effect of free anterolateral thigh perforator flap(ALTPF) in reconstruction of temporal scalp defect after blood circulation reconstruction surgery for moyamoya disease.Methods:From May 2020 to July 2022, 7 patients with scalp defect after revascularisation of moyamoya disease were treated in Department of Hand and Foot Microsurgery, Henan Provincial People’s Hospital (People’s Hospital of Zhengzhou University). The patients were 4 males and 3 females, aged 33-59 years old, at 43 years old in average. There were 5 defects in left tempus and 2 in right tempus. The sizes of scalp defect were 4.5 cm × 5.5 cm-7.5 cm × 9.5 cm. Debridement and VSD management were primarily performed. After wounds were stabilised, ultrasound location of perforator vessels of ALTPFs was performed. Having confirmed that the perforator vessels were suitable for the surgical requirements, flap transfers were then performed. The descending branch of the lateral femoral circumflex artery was end-to-side anastomosed with the superficial temporal artery, and the descending branch of the lateral femoral circumflex vein was end-to-end anastomosed with the superficial temporal vein. Postoperative follow-up was conducted through outpatient clinic visits, telephone and WeChat reviews. Appearance, texture of ALTPFs and the flap donor sites were observed in follow-ups. Comparisons of the changes of nervous system before and after surgery were made. Cognitive function of the patients was assessed with the Mini Mental State Examination (MMSE), together with the Activities of Daily Living (ADL) .Results:All 7 flaps survived. One flap had vascular compromise 6 hours after surgery, and was rectified after surgical intervention. All the patients were included in the postoperative follow-up for 7-33 (average 19) months. All flaps had good appearance with soft texture. There was no obvious difference in colour comparing with the skin around the recipient region. The donor sites healed well without hypertrophic scar. Examinations of nervous system of the patients were found the same as that before surgery. Using Manual Muscle Testing (MMT), the average limb muscle strength of the patients was 4 before surgery and 4 after surgery, without change; Using the Ashworth assessment scale, the average preoperative and postoperative limb muscle tension in this group of patients was 1, without change; The Berg balance scale was used to evaluate the patient's balance function, with an average score of 42 before surgery and 42 after surgery, without any changes; There was no change in limb sensation before and after surgery; Using the MMSE, the average preoperative score and postoperative score of this group of patients were 25 points, without any change. Using the modified Barthel index scoring standard, the average preoperative score for this group of patients was 75 points, and the average postoperative score was 79 points, and the ADL of the patient had improved to various levels.Conclusion:Reconstruction of scalp defect with free ALTPF after revascularisation of moyamoya disease has obvious advantages, such as it closes the wound quickly, prevents infection and achieves a good appearance. This surgical procedure can produce a good clinical effect.

Recommendations for the diagnosis and treatment of maternal SARS-CoV-2 infection / 中华围产医学杂志

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has spread worldwide and threatened human's health. With the passing of time, the epidemiology of coronavirus disease 2019 evolves and the knowledge of SARS-CoV-2 infection accumu-lates. To further improve the scientific and standardized diagnosis and treatment of maternal SARS-CoV-2 infection in China, the Chinese Society of Perinatal Medicine of Chinese Medical Association commissioned leading experts to develop the Recommendations for the Diagnosis and Treatment of Maternal SARS-CoV-2 Infection under the guidance of the Maternal and Child Health Department of the National Health Commission. This recommendations includes the epidemiology, diagnosis, management, maternal care, medication treatment, care of birth and newborns, and psychological support associated with maternal SARS-CoV-2 infection. It is hoped that the recommendations will effectively help the clinical management of maternal SARS-CoV-2 infection.

Efficacy analysis of anti-platelet in the treatment of high-risk non-disabling ischemic cerebrovascular events guided by point-of-care testing of CYP2C19 gene / 中华神经科杂志

Objective:To explore the efficacy and safety of different anti-platelet regimens in the treatment of high-risk non-disabling ischemic cerebrovascular events (HR-NICE) guided by point-of-care testing of CYP2C19 gene. Methods:A single-centre, prospective, randomised, open-label, and blinded endpoint design was uesd in the study. From July 2020 to January 2022, HR-NICE patients were enrolled in the Stroke Green Channel and Department of Neurology of Xuzhou Central Hospital, and all patients were scraped the buccal mucosa for screening for CYP2C19 loss-of-function allele carriers by point-of-care testing . Patients with intermediate metabolism were defined as those who carried 1 loss-of-function allele and patients with poor metabolism were those who carried 2 loss-of-function alleles. This study reduced the test turnaround time to 1 hour by using a fully automated medical polymerase chain reaction analyzer for a point-of-care test of CYP2C19 genotype. CYP2C19 loss-of-function allele carriers were divided according to the random number table method into the conventional treatment group (clopidogrel 75 mg, once a day), the ticagrelor group (ticagrelor 90 mg, twice a day) and the intensive dose group (clopidogrel 150 mg, once a day) separately combined with aspirin (100 mg, once a day) dual antiplatelet for 21 days. Baseline information, Acute Stroke Org 10172 Treatment Trial staging, 90-day modified Rankin Scale score, occurrence of adverse events and severe adverse events were collected for all the 3 groups. The primary efficacy outcome was new stroke within 90 days, and the primary safety outcome was severe or moderate bleeding within 90 days. Results:A total of 716 patients were included: 240 in the conventional treatment group, 240 in the ticagrelor group and 236 in the intensive dose group. There was no statistically significant difference between the 3 groups at baseline (all P>0.05). There were 26 cases (10.8%) with new stroke events in the conventional treatment group, 11 cases (4.6%) in the ticagrelor group and 4 cases (1.7%) in the intensive dose group, with statistically significant differences among the 3 groups (χ 2=19.28, P<0.05), and the differences between the conventional treatment group and the ticagrelor group (χ 2=6.59, P=0.010) and between the conventional treatment group and the intensive dose group (χ 2=16.83, P<0.001) were statistically significant, whereas the difference between the ticagrelor group and the intensive dose group was not statistically significant ( P>0.05). In the 3 groups, there was 1 case (0.4%) of severe bleeding in the conventional treatment group, 6 cases (2.5%) in the ticagrelor group and none in the intensive dose group, which showed statistically significant differences (χ 2=7.23, P<0.05), and there was statistically significant difference between the ticagrelor group and the intensive dose group ( P=0.030). Among the patients with intermediate CYP2C19 metabolism, there were 13 cases (13/158, 8.2%) with 90-day recurrent stroke in the conventional treatment group, 4 cases (4/153, 2.6%) in the ticagrelor group, and 0 case (0/159) in the intensive dose group, with statistically significant difference (χ 2=16.04, P<0.001), and the differences between the intensive dose group and the conventional treatment group were statistically significant (χ 2=13.64, P<0.001), whereas there was no statistically significant difference between the intensive dose group and the ticagrelor group ( P>0.05). In the patients with 90-day recurrent stroke in the intensive dose group, there was 0 case (0/159) with intermediate metabolism and 4 cases (4/77,5.2%) with poor metabolism, with statistically significant differences ( P=0.011), whereas there were no statistically significant differences in the conventional treatment group and the ticagrelor group ( P>0.05). Conclusions:Screening carriers of CYP2C19 loss-of-function alleles by point-of-care testing can quickly and precisely guide the treatment of patients with non-cardiogenic HR-NICE. An intensive clopidogrel dose of 150 mg, once a day combined with aspirin was effective in reducing stroke recurrence with less occurrence of any bleeding and adverse events, and patients with intermediate CYP2C19 metabolism may be the best population to benefit.

Survey on status quo of psychosomatic medical service ability and training needs among general practice resident physicians / 中华全科医师杂志

Objective:To investigate the current status of psychosomatic medical service competence and training needs among general practice resident physicians.Methods:An online questionnaire survey was conducted from August to September 2021, among general practice resident physicians selected by cluster sampling from 4 affiliated hospitals of Tongji University. The questionnaire contained the basic information, the self-assessment and training needs of psychosomatic medical service competence of participants, and psychosomatic medical service requirements of patients in the community.Results:A total of 159 questionnaires were distributed, and 140 were collected (88.1%). The survey showed that 25.7% (36/140) of participants believed that 50% or more patients had physical symptoms accompanied by emotional problems; 29.3% (41/140) thought that 50% or more patients had sleep problems, but 60.0% (84/140) of them failed to provide appropriate treatment. The rate of "core knowledge and concepts of psychosomatic medicine" was 47.5% (665/1 400) and the correct rate of "common psychosomatic diseases" was (64.6±23.4)%. Merely 21.4% (30/140) participants reported satisfaction with the psychosomatic medical service competence; 62.8% (88/140) respondents believed that the coverage rate of the above-mentioned competence training in the current general practice residential training program was less than 50%, and 66.4% (93/140) supported that more psychosomatic training was "necessary". The acceptance rate of online training, workshops, MDT, and clinical practice ranged from 56.4% (79/140) to 63.4% (89/140).Conclusions:The survey indicates that there are large needs for psychosomatic medical services among patients in community, but the competence and confidence of general practice resident physicians to provide the service are significantly insufficient. Therefore, it is suggested to strengthen the training of psychosomatic medical service competence in the general practice residency training program.

Correlation between vaccination doses and duration of positive nucleic acid or antigen tests among COVID-19 patients / 中华全科医师杂志

Objective:To investigate the relationship between vaccination doses and the duration of positive nucleic acid or antigen tests in Corona Virus Disease 2019 (COVID-19) patients during omicron epidemic.Methods:A cross-sectional study was conducted from December 26 to December 31, 2022 among COVID-19 patients from all community health service centers in 16 districts of Beijing municipality selected by multi-stage stratified cluster quota sampling method. A questionnaire was used to collect the basic information, vaccination doses, results of nucleic acid or antigen tests of all subjects. The subjects were divided into 5 groups according to the doses of COVID-19 vaccination: the non-vaccination group, the 1, 2, 3 and 4 doses vaccination group. The relationship between vaccination doses and the duration of positive nucleic acid or antigen tests was analyzed by univariate and multivariate logistic regression models.Results:A total of 10 506 COVID-19 cases were included in the study with the age of (43.3±13.7) years. The duration of positive nucleic acid or antigen tests was longer than 7 days in 59.4%(276/465), 51.5%(67/130), 50.6%(355/701), 46.1% (3 464/7 520) and 39.2%(662/1 690) of non-vaccination, and 1, 2, 3, 4 dose vaccination groups, respectively ( P<0.001). Multivariate logistic regression analysis showed that compared with non-vaccination patients, the vaccination dose was an independent protective factor for duration of positive nucleic acid or antigen tests>7 days, and the OR values were 0.7 (95% CI 0.5-0.9, P=0.015), 0.6 (95% CI 0.5-0.8, P<0.001) and 0.5 (95% CI 0.4-0.6, P<0.001) for 2, 3 and 4 doses of vaccination, respectively. Conclusion:The vaccination doses are independently related to the duration of positive nucleic acid or antigen tests in COVID-19 patients and the risk is gradually decreases with the increasing vaccination doses.

Analysis of revascularization strategies for elderly patients with ST-segment elevation myocardial infarction and multivessel disease / 中华老年医学杂志

Objective:To compare the effects of staged percutaneous coronary intervention(PCI)after emergency PCI and emergency culprit-only PCI on clinical outcomes of elderly patients with ST-segment elevation myocardial infarction(STEMI)and multivessel disease.Methods:A retrospective analysis was performed on 389 elderly patients with STEMI and multivessel lesions, aged ≥70 years and within 12 h of onset, admitted to the Clinical College of Thoracic Medicine, Tianjin Medical University, between January 2014 and September 2019.According to different revascularization strategies, enrolled patients were divided into the culprit-only PCI group(79.18%, 308)and the staged PCI group(20.82%, 81). Kaplan-Meier analysis and the Cox proportional hazards regression model were used to compare the incidences of major adverse cardiac and cerebrovascular events(MACCE), all-cause death, cardiac death, recurrent myocardial infarction, stroke and ischemia-driven revascularization between the two groups and to evaluate the effects of different revascularization strategies on MACCE and all-cause death.Then subgroup analysis was performed.Results:During a 56-month follow-up, 131 patients developed MACCE and 96 patients died.Compared with the culprit-only PCI group, the staged PCI group had a lower risk of MACCE( HR: 0.404, 95% CI: 0.227-0.716, P=0.002), all-cause death( HR: 0.354, 95% CI: 0.171-0.730, P=0.005), cardiac death( HR: 0.363, 95% CI: 0.157-0.838, P=0.018), and recurrent myocardial infarction( HR: 0.229, 95% CI: 0.055-0.953, P=0.043). There was no significant difference in the incidence of stroke or ischemia-driven revascularization between the two groups( P>0.05). The reduced risk with staged PCI for MACCE and for all-cause mortality persisted in all subgroups.Multivariate Cox proportional hazards regression revealed that, after adjusting for confounding factors, staged PCI was an independent protective factor for MACCE( HR: 0.44, 95% CI: 0.239-0.815, P=0.009)and for all-cause death( HR: 0.390, 95% CI: 0.90, P=0.020). Conclusion:Compared with culprit-only PCI, staged PCI can significantly improve the long-term prognosis of elderly patients ≥70 years with STEMI and multivessel disease within 12 h of onset.

Rutin Promotes Browning of 3T3-L1 Preadipocytes and Its Mechanism / 中国实验方剂学杂志

ObjectiveTo investigate the effect of rutin on the browning of 3T3-L1 preadipocytes and the mechanism. MethodCell counting kit-8 （CCK-8） assay was used to detect the effect of different concentration of rutin （3.125， 6.25， 12.5， 25， 50， 100， 200 μmol·L-1） on 3T3-L1 cell activity， and Western blot to examine the effect of rutin （12.5， 25， 50 μmol·L-1） on the expression of thermogenesis-associated proteins uncoupling protein 1 （UCP1）， PR domain containing 16 （PRDM16） and peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α） in adipocytes. After the optimal concentration of rutin was determined， the effect of rutin on lipid droplet formation in adipocytes was observed based on oil red O staining， and the expression of nuclear respiratory factor 1 （NRF1）， nuclear respiratory factor 2 （NRF2） and mitochondrial transcription factor A （TFAM）， which were the landmark proteins of mitochondrial biosynthesis， was detected by Western blot. ResultCompared with the blank group， 200 μmol·L-1 rutin inhibited 3T3-L1 cell activity （P<0.01）. Compared with the blank group， at the concentration of 12.5， 25， 50 μmol·L-1 rutin significantly promoted the expression of thermogenesis-associated proteins （UCP1， PRDM16， and PGC-1α） （P<0.01）， which was determined as the optimal concentration. Compared with the blank group， 50 μmol·L-1 rutin significantly increased the immunofluorescence intensity of mitochondrial UCP1 protein in 3T3-L1 cells （P<0.01） and the expression of the markers of mitochondrial biosynthesis （NRF1， NRF2， and TFAM） （P<0.01）. In addition， 50 μmol·L-1 rutin significantly inhibited lipid droplet formation of 3T3-L1 adipocytes （P<0.01）. ConclusionRutin inhibited lipid droplet deposition in 3T3-L1 adipocytes and increased the expression of thermogenesis-related proteins （UCP1， PRDM16， and PGC-1α） and markers of mitochondrial biosynthesis （NRF1， NRF2， and TFAM）， thereby inducing the browning of 3T3-L1 adipocytes. This lays a basis for the development of drugs that safely regulate the browning of white cells.

Mechanisms of Euphorbia fischeriana steud. alcohol extracts intreatment of HCC based on network pharmacology and experiment verification / 中国药理学通报

Aim To investigate the molecular mechanisms of alcohol extracts of Euphorbia fischeriana steud. against hepatocellular carcinoma (HCC) through a combination of network pharmacology analysis and experimental validation. Methods The active ingredients and targets of alcohol extracts of Euphorbia fischeriana steud. were determined through TCMSP, Swiss ADME, Swiss Target Prediction database and references. The databases DisGeNET and GeneCards were employed to screen potential HCC-related genes. Venny platform, STRING platform and Cytoscape software were applied to construct active ingredient-target-disease and protein-protein interaction (PPI) network maps. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses were performed using the DAVID database. To assess the effects of Euphorbia fischeriana steud. alcohol extracts on BEL-7402 cells, the proliferation and apoptosis were detected by CCK-8, EdU and flow cytometry assays, and the related protein levels of JAK2/STAT3 pathway were analyzed by Western blot. Additionally, H22 hepatocellular carcinoma mouse model was used to evaluate the in vivo efficacy of Euphorbia fischeriana steud. alcohol extracts. Results A total of 916 HCC targeted genes, 30 active ingredients containing the related 567 potential targeted genes, and 115 intersection targets of disease and compounds were obtained. KEGG enrichment analysis identified JAK2/STAT3 signaling as a critical pathway. In vitro experiments showed the alcohol extracts of Euphorbia fischeriana steud. could inhibit proliferation, promote apoptosis and suppress JAK2/STAT3 signaling pathway in a dose-dependent manner in BEL-7402 cells. In addition, the alcohol extracts of Euphorbia fischeriana steud., either alone or in combination with sorafenib, dramatically blocked tumor growth in in vivo tests. Conclusions Euphorbia fischeriana steud. alcohol extracts have anti-cancer effects in HCC, and the molecular mechanisms may be connected to the regulation of JAK2/STAT3 signaling pathway.

Investigation of extrauterine growth restriction in very preterm infants in Chinese neonatal intensive care units / 中华儿科杂志

Objective: To comprehensively assess the current status of extrauterine growth restriction (EUGR) in very preterm infants (VPI) and its associated factors in Chinese neonatal intensive care units (NICU). Methods: In this cohort study, 6 179 preterm infants born at <32 weeks' gestation were included, who were admitted to 57 hospitals in the China Neonatal Network in 2019 and hospitalized for ≥7 days. EUGR was evaluated by a cross-sectional definition (weight at discharge<10th percentile for postmenstrual age), a longitudinal definition (decline in weight Z score>1 from birth to discharge), and weight growth velocity. The comparison between infants with and without EUGR was conducted by t-test, Mann-Whitney U test or χ2 test as appropriate. Multivariable Logistic regression models were used to evaluate associations between EUGR with different definitions and maternal and neonatal factors, clinical practices, and neonatal morbidities. Results: A total of 6 179 VPI were enrolled in the study, with a gestational age of (29.8±1.5) weeks and birth weight of (1 365±304) g; 56.2% (3 474) of them were male. Among them, 48.4% (2 992 VPI) were cross-sectional EUGR and 74.9% (4 628 VPI) were longitudinal EUGR. Z score of weight was (0.13±0.78) at birth and decrease to (-1.35±0.99) at discharge. The weight growth velocity was 10.13 (8.42, 11.66) g/(kg·d). Multivariate Logistic regression analysis showed that among the influential factors that could be intervened after birth, late attainment of full enteral feeds (ORadjust=1.01, 95%CI 1.01-1.02, P<0.001; ORadjust=1.01, 95%CI 1.01-1.02, P<0.001), necrotizing enterocolitis≥Ⅱstage (ORadjust=2.64, 95%CI 1.60-4.35, P<0.001; ORadjust=1.62, 95%CI 1.10-2.40, P<0.001) and patent ductus arteriosus (ORadjust=1.94, 95%CI 1.50-2.51, P<0.001; ORadjust=1.63, 95%CI 1.29-2.06, P<0.001) were all associated with increased risks of both cross-sectional and longitudinal EUGR. In addition, late initiation of enteral feeds (ORadjust=1.06, 95%CI 1.02-1.09, P=0.020) and respiratory distress syndrome (ORadjust=1.45, 95%CI 1.24-1.69, P<0.001) were all associated with cross-sectional EUGR. Breast milk feeding (ORadjust=1.33, 95%CI 1.05-1.68, P<0.001) was associated with a higher risk of longitudinal EUGR. Conclusions: The incidence of EUGR in VPI in China is high. Some modifiable risk factors provide priorities to improve postnatal growth for VPI. Nutritional management of VPI and the efforts to decrease the incidence of complications are still the focus of clinical management in China.

Aureane-type sesquiterpene tetraketides as a novel class of immunomodulators with interleukin-17A inhibitory activity

Interleukin (IL)-17A, a pro-inflammatory cytokine, is a fundamental function in the onset and advancement of multiple immune diseases. To uncover the primary compounds with IL-17A inhibitory activity, a large-scale screening of the library of traditional Chinese medicine constituents and microbial secondary metabolites was conducted using splenic cells from IL-17A-GFP reporter mice cultured under Th17-priming conditions. Our results indicated that some aureane-type sesquiterpene tetraketides isolated from a wetland mud-derived fungus, Myrothecium gramineum, showed remarkable IL-17A inhibitory activity. Nine new aureane-type sesquiterpene tetraketides, myrogramins A-I ( 1, 4- 11), and two known ones ( 2 and 3) were isolated and identified from the strain. Compounds 1, 3, 4, 10, and 11 exhibited significant IL-17A inhibitory activity. Among them, compound 3, with a high fermentation yield dose-dependently inhibited the generation of IL-17A and suppressed glycolysis in splenic cells under Th17-priming conditions. Strikingly, compound 3 suppressed immunopathology in both IL-17A-mediated animal models of experimental autoimmune encephalomyelitis and pulmonary hypertension. Our results revealed that aureane-type sesquiterpene tetraketides are a novel class of immunomodulators with IL-17A inhibitory activity, and hold great promise applications in treating IL-17A-mediated immune diseases.

Mulberry leaf flavonoids activate BAT and induce browning of WAT to improve type 2 diabetes via regulating the AMPK/SIRT1/PGC-1α signaling pathway / 中国天然药物

Mulberry (Morus alba L.) leaf is a well-established traditional Chinese botanical and culinary resource. It has found widespread application in the management of diabetes. The bioactive constituents of mulberry leaf, specifically mulberry leaf flavonoids (MLFs), exhibit pronounced potential in the amelioration of type 2 diabetes (T2D). This potential is attributed to their ability to safeguard pancreatic β cells, enhance insulin resistance, and inhibit α-glucosidase activity. Our antecedent research findings underscore the substantial therapeutic efficacy of MLFs in treating T2D. However, the precise mechanistic underpinnings of MLF's anti-T2D effects remain the subject of inquiry. Activation of brown/beige adipocytes is a novel and promising strategy for T2D treatment. In the present study, our primary objective was to elucidate the impact of MLFs on adipose tissue browning in db/db mice and 3T3-L1 cells and elucidate its underlying mechanism. The results manifested that MLFs reduced body weight and food intake, alleviated hepatic steatosis, improved insulin sensitivity, and increased lipolysis and thermogenesis in db/db mice. Moreover, MLFs activated brown adipose tissue (BAT) and induced the browning of inguinal white adipose tissue (IWAT) and 3T3-L1 adipocytes by increasing the expressions of brown adipocyte marker genes and proteins such as uncoupling protein 1 (UCP1) and beige adipocyte marker genes such as transmembrane protein 26 (Tmem26), thereby promoting mitochondrial biogenesis. Mechanistically, MLFs facilitated the activation of BAT and the induction of WAT browning to ameliorate T2D primarily through the activation of AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) signaling pathway. These findings highlight the unique capacity of MLF to counteract T2D by enhancing BAT activation and inducing browning of IWAT, thereby ameliorating glucose and lipid metabolism disorders. As such, MLFs emerge as a prospective and innovative browning agent for the treatment of T2D.

Advances in the classification and treatment of isolated superior mesenteric artery dissection / 中华外科杂志

Isolated superior mesenteric artery dissection (ISMAD) has attracted more and more clinicians' attention in recent years. Patients onset of ISMAD often present with abdominal pain. The misdiagnosis or miss diagnosis is common because of the non-specific symptoms and signs, which even can endanger lives in serious cases. Imaging classification is of great significance for diagnosis and treatment of ISMAD. The Sakamoto classification and the Yun classification are two classical classified methods. However, with the further study of ISMAD, various new classifications emerge. Conservative treatment was once considered as the preferred. As the rapid development of endovascular therapy and the great progress of new devices, stenting therapy can significantly improve symptoms and achieve satisfactory long-term effects, and be even expected to become the preferred method for clinical therapy of ISMAD. However, the long-term effects of endovascular therapy still need a large number of follow-up data, and complications after stent implantation can't be ignored.

Pulmonary granular cell tumors: a clinicopathological analysis of five cases / 中华病理学杂志

Objective: To investigate the clinicopathological features of pulmonary granular cell tumors (pGCTs) and to improve the diagnostic accuracy of the tumor. Methods: A total of 5 pGCTs were diagnosed from February 2016 to January 2022 at Shanghai Pulmonary Hospital, Tongji University School of Medicine and Fudan University Shanghai Cancer Center, China. Immunohistochemical staining, and analysis of the clinicopathological characteristics were performed. Results: The average age of the pGCTs patients was 46 years (ranging from 24 to 54 years), with 3 females and 2 males. One case occurred in the bronchus with multiple nodules in the lung, 2 cases occurred in the bronchial opening, and 2 cases were solitary nodules in the lung. The maximum diameter of the tumors ranged from 12 to 15 mm (mean size 14 mm). Microscopically, the tumor showed infiltrative growth and consisted of round, oval or polygonal cells. Abundant eosinophilic cytoplasm was noted, and the nucleoli were prominent. None of the 5 cases showed any mitosis or necrosis. Immunohistochemical and histochemical study showed positive staining for S-100 (5/5), SOX10 (5/5), Vimentin (5/5), TFE3 (4/5), PAS (3/5), and amylase-digested-PAS (3/5), while 4 cases were negative for CD68. TFE3 FISH analyses on 2 cases showed that no signal abnormality was detected in these 2 cases. The average proliferation index of Ki-67 was 2.2% (range 0-5%). There was no recurrence in 4 cases of pGCTs with a follow-up time ranging from 2 months to 60 months. Conclusions: pGCTs are very rare tumors, most likely originating from Schwann cells. Immunohistochemical staining is the conventional diagnostic tool for pGCTs diagnosis. Recognition of this entity is essential for pathologists to avoid misdiagnosis and unnecessary treatments.