Mutational Signatures Analysis of Micropapillary Components and Exploration of ZNF469 Gene in Early-stage Lung Adenocarcinoma with Ground-glass Opacities / 中国肺癌杂志

BACKGROUND@#In China, lung cancer remains the cancer with the highest incidence and mortality rate. Among early-stage lung adenocarcinomas (LUAD), the micropapillary (MPP) component is prevalent and typically exhibits high aggressiveness, significantly correlating with early metastasis, lymphatic infiltration, and reduced five-year survival rates. Therefore, the study is to explore the similarities and differences between MPP and non-micropapillary (non-MPP) components in malignant pulmonary nodules characterized by GGOs in early-stage LUAD, identify unique mutational features of the MPP component and analyze the relationship between the ZNF469 gene, a member of the zinc-finger protein family, and the prognosis of early-stage LUAD, as well as its correlation with immune infiltration.@*METHODS@#A total of 31 malignant pulmonary nodules of LUAD were collected and dissected into paired MPP and non-MPP components using microdissection. Whole-exome sequencing (WES) was performed on the components of early-stage malignant pulmonary nodules. Mutational signatures analysis was conducted using R packages such as maftools, Nonnegative Matrix Factorization (NMF), and Sigminer to unveil the genomic mutational characteristics unique to MPP components in invasive LUAD compared to other tumor tissues. Furthermore, we explored the expression of the ZNF469 gene in LUAD using The Cancer Genome Atlas (TCGA) database to investigate its potential association with the prognosis. We also investigated gene interaction networks and signaling pathways related to ZNF469 in LUAD using the GeneMANIA database and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Lastly, we analyzed the correlation between ZNF469 gene expression and levels of immune cell infiltration in LUAD using the TIMER and TISIDB databases.@*RESULTS@#MPP components exhibited a higher number of genomic variations, particularly the 13th COSMIC (Catalogue of Somatic Mutations in Cancer) mutational signature characterized by the activity of the cytidine deaminase APOBEC family, which was unique to MPP components compared to non-MPP components in tumor tissues. This suggests the potential involvement of APOBEC in the progression of MPP components in early-stage LUAD. Additionally, MPP samples with high similarity to APOBEC signature displayed a higher tumor mutational burden (TMB), indicating that these patients may be more likely to benefit from immunotherapy. The expression of ZNF469 was significantly upregulated in LUAD compared to normal tissue, and was associated with poor prognosis in LUAD patients (P<0.05). Gene interaction network analysis and GO/KEGG enrichment analysis revealed that COL6A1, COL1A1, COL1A2, TGFB2, MMP2, COL8A2 and C2CD4C interacted with ZNF469 and were mainly involved in encoding collagen proteins and participating in the constitution of extracellular matrix. ZNF469 expression was positively correlated with immune cell infiltration in LUAD (P<0.05).@*CONCLUSIONS@#The study has unveiled distinctive mutational signatures in the MPP components of early-stage invasive LUAD in the Asian population. Furthermore, we have identified that the elevated expression of mutated ZNF469 impacts the prognosis and immune infiltration in LUAD, suggesting its potential as a diagnostic and prognostic biomarker in LUAD.

Effects of Tongfengning（痛风宁） on Intestinal Flora and Intestinal Uric Acid Metabolism in Model Mice of Hyperuri⁃cemia of Spleen Deficiency with Exuberance of Dampness Syndrome / 中医杂志

ObjectiveTo explore the possible mechanisms of Tongfengning （痛风宁， TFN） in treating hyperuricemia （HUA） of spleen deficiency with exuberance of dampness syndrome. MethodsTen of 60 mice were randomly selected， and were fed with regular diet as the control group， while the remaining 50 mice were fed with high-fat and high-sugar diet combined with excessive exercise and potassium oxonate-allopurinol suspension to establish an HUA animal model of syndrome of spleen deficiency with exuberance of dampness. After the successful modeling， in order to better observe the effects of TFN on the intestinal microbiota of the model mice， a mixed antibiotic suspension was administered by gavage to induce further dysbiosis of the intestinal microbiota in the model mice. Fifty sucessfully modeled mice were randomly divided into model group， TFN group， allopurinol group， probiotics group， and an allopurinol + probiotics group， 10 in each group. The TFN group was administered TFN liquid at a dosage of 19.11 g/（kg·d） by gavage. The allopurinol group was administered allopurinol suspension at a dosage of 78 mg/（kg·d） by gavage. The probiotics group was administered live combined Bifidobacterium and Lactobacillus tablets suspension at a dosage of 3 g/（kg·d） by gavage. The allopurinol + probiotics group was administered allopurinol at a dosage of 78 mg/（kg·d） and live combined Bifidobacterium and Lactobacillus tablets suspension at a dosage of 3 g/（kg·d） by gavage. The control group and model group were administered normal saline at a dosage of 19.11 ml/（kg·d） by gavage. The interventions were continued for 21 days. In order to maintain a stable high blood uric acid state， all groups but the control group continued modeling while receiving drug intervention. The changes in spleen deficiency syndrome scores， blood uric acid levels， microbial community structure， acetic acid and butyric acid content in intestinal lavage fluid， adenosine deaminase （ADA） and xanthine oxidase （XOD） content in small intestine tissue， as well as ATP-binding cassette transporter G2 （ABCG2）， glucose transporter 9 （GLUT9） protein and mRNA expression in the small intestine tissue were compared among the groups of mice. ResultsCompared with the control group， the model group showed increased spleen deficiency syndrome scores， blood uric acid levels， relative abundance of phylum Firmicutes， Firmicutes/Bacteroidetes ratio， abundance of Bacteroides genus， Klebsiella genus， and Enterococcus genus， acetic acid content in intestinal lavage fluid， ADA and XOD content in small intestine tissue， as well as GLUT9 protein and mRNA expression （P<0.05）. The number of operational taxonomic units （OTUs） of intestinal microbiota， relative abundance of Bacteroidetes phylum， abundance of Lactobacillus genus and uncultured Bacteroides genus， butyric acid content in intestinal lavage fluid， and ABCG2 protein and mRNA expression in small intestine tissue were significantly decreased （P＜0.05）. Compared with the model group， in the group treated with TFN， probiotics， and allopurinol + probiotics， the spleen deficiency syndrome score， blood uric acid level， relative abundance of Firmicutes， acetic acid content in intestinal lavage fluid， ADA and XOD content in small intestine tissue， GLUT9 protein and mRNA expression significantly decreased. The number of gut microbiota OTUs， relative abundance of proteobacteria， butyric acid content in intestinal lavage fluid， ABCG2 protein and mRNA expression in small intestine tissue significantly increased （P＜0.05）. In the probiotics group， the ratio of Firmicutes to Bacteroidetes decreased. In the TFN group， the abundance of Lactobacillus and uncultured Bacteroidetes significantly increased， while the abundance of Parabacteroides， Klebsiella， and Enterococcus significantly decreased （P＜0.05）. Compared with the TFN group， allopurinol group and the probiotics group showed elevated blood uric acid levels， abundance of Bacteroidetes， ADA and XOD levels in intestinal tissue， and GLUT9 mRNA expression. The relative abundance of Firmicutes， abundance of lactobacilli， and ABCG2 mRNA expression significantly decreased. The probiotics group showed elevated GLUT9 protein expression in intestinal tissue. The probiotics group and the allopurinol plus probiotics group showed significantly higher scores for spleen deficiency syndrome in mice， and lower levels of butyric acid in mouse intestinal lavage fluid. The allopurinol group showed decreased numbers of OTUs in mouse intestinal flora， decreased abundance of proteobacteria， and butyric acid levels in intestinal lavage fluid. The allopurinol group also showed decreased ABCG2 protein expression in intestinal tissue， increased acetic acid levels in intestinal lavage fluid， increased abundance of Klebsiella， and significantly elevated GLUT9 protein expression （P＜0.05）. ConclusionsThe treatment of HUA with TFN may be associated with the regulation of intestinal probiotics （such as lactobacilli） and pathogenic bacteria （such as Klebsiella）， as well as the production of bacterial metabolites such as acetic acid and butyric acid. It may also involve reducing the expression of ADA and XOD in the intestines， decreasing intestinal uric acid production， upregulating the expression of intestinal epithelial urate transporter ABCG2， downregulating GLUT9 expression， and promoting intestinal uric acid excretion. These factors are related to the syndrome of spleen deficiency with exuberance of dampness.

A study on the suitability of HD-V2 film in ultra-high dose-rate electron beam dosimetry / 中华放射肿瘤学杂志

Objective:To evaluate the usability of Gafchromic HD-V2 film for dose dosimetry in the ultra-high dose-rate (UD) electron beam from a modified medical linac, and to investigate the response between the energy and dose-rate dependence to the film.Methods:The HD-V2 film was utilized to measure the average dose-rate of the UD electron beam. The measured result was compared with those by advanced Markus chamber and alanine pellets. And characteristics of the UD electron beam were also measured by HD-V2 film. Energy dependence of HD-V2 film at three beam energies (6 MV X-ray, 9 MeV and 16 MeV electron beam) was investigated by obtaining and comparing the calibration curves based on the clinical linear accelerator in the dose range of 10-300 Gy. The dose-rate dependence of HD-V2 film was also studied by varying the dose rate among 0.03 Gy/s, 0.06 Gy/s and 0.1 Gy/s, and range of 100-200 Gy/s.Results:The measured average maximum dose-rate of 9 MeV UD electron beam at source skin distance (SSD) 100 cm was approximately 121 Gy/s using HD-V2 film, consistent with the results by advanced Markus chamber and alanine pellets. The measured percentage depth dose (PDD) curve parameters of the UD electron beam were similar to the conventional 9 MeV beam. The off-axis dose distribution of the UD electron beam showed the highest central axis, and the dose was gradually decreased with the increase of off-axis distance. The energy dependence of HD-V2 film had no dependency of 6 MV and 9, 16 MeV while measuring the dose in the range from 20 to 300 Gy. The HD-V2 film had no significant dose-rate dependency at the dose rate of 0.03 Gy/s, 0.06 Gy/s and 0.1 Gy/s for the clinical linear accelerator. Likewise, there was also no dose-rate dependence in the range 100-200 Gy/s in the modified machine.Conclusion:HD-V2 film is suitable for measuring ultra-high dose rate electron beam, independent of energy and dose rate.

Devascularized bone surface culture for identification of microorganisms for osteomyelitis / 中华创伤骨科杂志

Objective:To evaluate devascularized bone surface culture for identification of microorganisms for osteomyelitis.Methods:A prospective study was conducted to include the eligible patients who were diagnosed with osteomyelitis and treated at Division of Orthopaedics and Traumatology, Department of Orthopaedics and Traumatology, Nanfang Hospital from December 2021 to January 2023. Their infected bone tissues were collected for both bone sample culture (BSC) and general sample culture (GSC). For BSC, the devascularized bone fragments, harvested intraoperatively, were put flat on sterile culture plates with solidified agar, their surface was gently covered with cooled and molten tryptone soy agar, and then the plates with bone samples were incubated at 37 ℃ with 5% CO 2. Meanwhile, 5 suspected samples of infected bone tissue were randomly harvested by 5 independent instruments for laboratory GSC. The culture time, bacterial species, and bacterial positive rate were compared between the 2 culture methods. Results:Included were a total of 73 patients [59 males and 14 females with an age of 49.0(31.0, 58.5) years]. The culture time for BSC [1 (1, 1) d] was significantly shorter than that for GSC [3 (2, 3) d], and the total positive rate of BSC [78.1% (57/73)] was significantly higher than that of GSC [61.6% (45/73)] ( P<0.05). The bacterial species cultured by GSC were consistent with those cultured by BSC. Conclusion:In identification of microorganisms for osteomyelitis, since BSC may be quicker and lead to a higher positive rate of bacterial culture than GSC, it can be used as an optional choice besides GCS.

Efficacy of implant surface culture in identification of microorganisms for fracture device-related infection: a preliminary analysis / 中华创伤骨科杂志

Objective:To evaluate the efficacy of implant surface culture in identification of pathogens for fracture device-related infection.Methods:A prospective study was conducted to include the eligible patients who were diagnosed with infection after fracture fixation and needed surgical removal of the implants according to treatment principles at Division of Orthopaedics and Traumatology, Department of Orthopaedics and Traumatology, Nanfang Hospital from November 2020 to January 2023. With informed consent, after rinsing with aseptic normal saline twice, their implants were gently covered with a thin layer of tryptone soy agar medium. Thereafter, the implants were incubated at 37 ℃ with 5% CO 2. Changes on the surface and in the surroundings of the implants were observed every day for consecutive 2 weeks to avoid drying up by supplementing the medium when necessary. Once pathogen colonies formed, samples were collected at 3 independent sites using sterile swabs for laboratory identification. Comparisons were made between the samples from implant surface culture and the intraoperative multisite samples from conventional culture. Results:Included were a total of 75 patients [56 males and 19 females with an age of (46.2±15.4) years]. The most common infection site was the tibia (37 cases), and the most common type of implants was plate and screw (59 cases). The positive rate of implant surface culture was significantly higher than that of conventional culture (86.7% vs. 52.0%, P<0.001). 80.5% (29/36) of the negative patients detected by the conventional culture obtained positive results by the implant surface culture; three of the positive patients detected by the conventional culture obtained negative results by the implant surface culture. The culture results were positive by both culture methods in 36 patients, and consistent by both culture methods in 35 patients, yielding a consistent rate of 97.2% (35/36). The time for implant surface culture was significantly shorter than that for conventional culture [1 (1, 2) d versus 3 (3, 4) d] ( P<0.001). Of the 65 positive patients by the implant surface culture, 59 were detected with monomicrobial infection, with Staphylococcus aureus on the top (29 cases). Conclusion:As the implant surface culture, a novel method, may be superior to the conventional culture in a significantly higher positive rate and a shorter culture time, it may be used as an effective adjunct to the conventional culture in identification of pathogens for fracture device-related infection.

Application of "eliminating stagnation and bloodletting/fire needling" in treatment of jingjin diseases / 中国针灸

Based on the development of conditions, the etiology and pathogenesis of jingjin (muscle region of meridian) diseases are summarized as 3 stages, i.e. stagnation due to over-exertion at early stage, manifested by tendon-muscle contracture and tenderness; cold condition due to stagnation, interaction of stasis and cold, resulting in clustered nodules at the middle stage; prolonged illness and missed/delayed treatment, leading to tendon-muscle contracture and impairment of joint function at the late stage. It is proposed that the treatment of jingjin diseases should be combined with the characteristic advantages of fire needling and bloodletting technique, on the base of "eliminating stagnation and bloodletting/fire needling". This combined therapy warming yang to resolve stasis and dispels cold to remove nodules, in which, eliminating the stagnation is conductive to the tissue regeneration, and the staging treatment is delivered in terms of the condition development at different phases.

Correlation between cognitive function and resting-state interhemispheric voxel-mirrored homotopic connectivity in patients with chronic schizophrenia / 四川精神卫生

BackgroundCognitive impairment， a core clinical feature of schizophrenia， is considered to be associated with the aberrant functional connectivity in patients with schizophrenia， whereas previous studies on the characteristics of cognitive impairment in patients with chronic schizophrenia and its correlation with interhemispheric voxel-mirrored homotopic connectivity （VMHC） are somewhat inadequate. ObjectiveTo investigate the characteristics of cognitive impairment in patients with chronic schizophrenia who are clinically stable on their antipsychotic medication， and to explore its correlation with resting-state interhemispheric VMHC， so as to provide theoretical basis for the identification of neurobiological mechanism possibly responsible for cognitive impairment in chronic schizophrenia. MethodsA total of 15 patients with chronic schizophrenia who met the criteria of the International Classification of Diseases， tenth edition （ICD-10） and hospitalized in Suzhou Guangji Hospital from January 2021 to December 2022 were included. Another 15 healthy community-dwelling individuals were concurrently recruited. All participants were requested to complete the Positive and Negative Symptom Scale （PANSS）， Repeatable Battery for the Assessment of Neuropsychological Status （RBANS） and resting-state functional Magnetic Resonance Imaging （rs-fMRI） scanning to evaluate their mental symptoms， cognitive function and interhemispheric functional connectivity. The rs-fMRI data were analyzed with VMHC method. Then Pearson correlation analysis was performed to examine the correlation between VMHC values of regions of interest and scores of RBANS and PANSS within patient group. ResultsPatient group obtained lower scores than control group based on RBANS immediate memory， visuospatial/constructional， language， attention and total score， with statistically significant differences （t=-2.853， -2.107， -5.576， -7.108， -5.354， P<0.05 or 0.01）. The VMHC values of left superior occipital gyrus （t=-5.188， P<0.05） and right cuneus （t=-5.188， P<0.05） in patient group were lower than those in control group， with statistical difference. Correlation analysis denoted that the VMHC values of left superior occipital gyrus （r=0.612， P=0.015） and right cuneus （r=0.612， P=0.015） were positively correlated with visuospatial/constructional index score in RBANS. ConclusionThe resting-state VMHC is abnormal in left superior occipital gyrus and right cuneus of patients with chronic schizophrenia， and yields a correlation with the visuospatial/constructional performance of patients. ［Funded by Suzhou Science and Technology Development Plan Project （number， SKJYD2021131； SKJY2021143）］

Machine learning modeling identifies hypertrophic cardiomyopathy subtypes with genetic signature / 医学前沿

Previous studies have revealed that patients with hypertrophic cardiomyopathy (HCM) exhibit differences in symptom severity and prognosis, indicating potential HCM subtypes among these patients. Here, 793 patients with HCM were recruited at an average follow-up of 32.78 ± 27.58 months to identify potential HCM subtypes by performing consensus clustering on the basis of their echocardiography features. Furthermore, we proposed a systematic method for illustrating the relationship between the phenotype and genotype of each HCM subtype by using machine learning modeling and interactome network detection techniques based on whole-exome sequencing data. Another independent cohort that consisted of 414 patients with HCM was recruited to replicate the findings. Consequently, two subtypes characterized by different clinical outcomes were identified in HCM. Patients with subtype 2 presented asymmetric septal hypertrophy associated with a stable course, while those with subtype 1 displayed left ventricular systolic dysfunction and aggressive progression. Machine learning modeling based on personal whole-exome data identified 46 genes with mutation burden that could accurately predict subtype propensities. Furthermore, the patients in another cohort predicted as subtype 1 by the 46-gene model presented increased left ventricular end-diastolic diameter and reduced left ventricular ejection fraction. By employing echocardiography and genetic screening for the 46 genes, HCM can be classified into two subtypes with distinct clinical outcomes.

Efficacy and safety of LY01005 versus goserelin implant in Chinese patients with prostate cancer: A multicenter, randomized, open-label, phase III, non-inferiority trial / 中华医学杂志(英文版)

BACKGROUND@#LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer.@*METHODS@#We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels.@*RESULTS@#On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]).@*CONCLUSION@#LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile.@*TRIAL REGISTRATION@#ClinicalTrials.gov, NCT04563936.

Traditional Chinese Medicine Diagnosis and Treatment of Neuropathic Pain from Theory of Chronic Pain Entering Collaterals / 中国实验方剂学杂志

Neuropathic pain is a clinical symptom with complex mechanisms and high incidence. The commonly used analgesics have limited efficacy and can cause serious side effects. The theory of chronic pain entering collaterals was proposed by YE Tianshi， a famous physician focusing on warm diseases in the Qing dynasty， on the basis of the ancient therapies for pain. This theory is particularly suitable for the diagnosis and treatment of neuropathic pain in view of the clinical course and manifestations. The chronic neuropathic pain can enter the Yin collateral in deeper sites. The pathogenesis of neuropathic pain is summarized as a deficiency in origin and excess in superficiality. The root cause is the dysfunction of Zang-Fu organs， mainly the liver, kidney and heart， while the superficial causes are phlegm and stasis caused by the obstructed Qi and blood movement due to the consumption of Qi and blood in collaterals. Accordingly， the therapies such as dispelling blood stasis， resolving phlegm， and dredging collaterals should be adopted. This paper expounds the traditional Chinese medicine （TCM） pathogenesis and treatment of neuropathic pain， enriching the knowledge and providing new ideas for the TCM prevention and treatment of this disease as a collateral disease.

Rapid identification of components in Wuzhuyu Decoction using UHPLC Q-Exactive Orbitrap MS~n and molecular network technology / 中国中药杂志

Wuzhuyu Decoction, the classical formula recorded in the Treatise on Febrile Diseases(Shang Han Lun), has been included in the Catalogue of Ancient Classic Prescriptions(the First Batch). Consisting of Euodiae Fructus, Ginseng Radix et Rhizoma, Zingiberis Rhizoma Recens, and Jujubae Fructus, it is effective in warming the middle, tonifying deficiency, dispelling cold, and descending adverse Qi, and is widely applied clinically with remarkable efficacies. For a classical formula, the chemical composition is the material basis and an important premise for quantity value transfer. This study aimed to establish a rapid identification method of chemical components in Wuzhuyu Decoction by high-resolution mass spectrometry(HR-MS) and molecular network. AQUITY UPLC BEH C_(18) column(2.1 mm×100 mm, 1.7 μm) was used for sample separation, and acetonitrile-0.1% formic acid in water was used as mobile phases for gradient elution. Q-Exactive Orbitrap MS data were collected in positive and negative ion modes, and GNPS molecular network was plotted according to the similarity of MS/MS fragmentation modes. Cytoscape 3.6.1 was used to screen molecular clusters with similar structures. Finally, the chemical components of Wuzhuyu Decoction were rapidly identified according to the controls, as well as the information of retention time, accurate relative molecular weight of HR-MS, and MS/MS multistage fragments. A total of 105 chemical components were identified in Wuzhuyu Decoction. This study can provide data for the follow-up quality control, standard substance research, and pharmacodynamic material research on Wuzhuyu Decoction, as well as references for the rapid qualitative analysis of the chemical components of Chinese medicine.

Research progress in multi-body system dynamics modeling in stomatology / 中华口腔医学杂志

The stomatognathic system is an organic combination of bone, dentition, joints, masticatory muscles and innervation nerves. It is an organ system for the human body to perform mastication, speech, swallowing and other important functions. Due to the complex anatomical structure of stomatognathic system and ethical limitations, it is difficult to directly measure the movement and force by using the biomechanical experimental methods. Multi-body system dynamics is an important tool to study the kinetics and force of a multi-body system, which consists of several objects with relative motion. We can use the method of multi-body system dynamics simulation in engineering to study the movement, soft tissue deformation and force transfer of this complex stomatognathic system. This paper briefly introduces the history and application methods of multi-body system dynamics and the commonly used modeling methods. The application and research progress of multi-body system dynamics modeling methods in the field of stomatology was emphatically summarized, development prospects of current research and difficulties were put forward.

Research progress in pharmacological effects of Aralia elata / 浙江大学学报·医学版

The traditional Chinese medicine Aralia elata (Miq.) Seem., also known as Aralia mandshurica, has the effect of "tonifying Qi and calming the mind, strengthening the essence and tonifying the kidneys, and dispelling wind and invigorating blood circulation". It is used in the treatment of neurasthenia, Yang deficiency and Qi deficiency, kidney Qi deficiency, spleen Yang deficiency, water-dampness stagnation, thirst, and bruises. Aralia elata saponins are the main components for the pharmacological effects. From the perspective of modern pharmacological science, Aralia elata has a wide range of effects, including anti-myocardial ischaemia and alleviation of secondary myocardium ischemic reperfusion injury by regulating ionic homeostasis, anti-tumor activity by inhibiting proliferation, promoting apoptosis and enhancing immunity, hypoglycemia and lipid lowering effects by regulating glucose and lipid metabolism, and hepato-protective, neuroprotective, anti-inflammatory/analgesic effects. The studies on pharmacological mechanisms of Aralia elata will be conducive to its development and application in the future. This article reviews the research progress of Aralia elata domestically and internationally in the last two decades and proposes new directions for further research.

Effectiveness of proximal femur bionic nail for intertrochanteric fracture in the elderly / 中国修复重建外科杂志

OBJECTIVE@#To evaluate effectiveness of proximal femur bionic nail (PFBN) in treatment of intertrochanteric fractures in the elderly compared to the proximal femoral nail antirotation (PFNA).@*METHODS@#A retrospective analysis was made on 48 geriatric patients with intertrochanteric fractures, who met the selection criteria and were admitted between January 2020 and December 2022. Among them, 24 cases were treated with PFBN fixation after fracture reduction (PFBN group), and 24 cases were treated with PFNA fixation (PFNA group). There was no significant difference in baseline data such as age, gender, cause of injury, side and type of fracture, time from injury to operation, and preoperative mobility score, American Society of Anesthesiologists (ASA) score, Alzheimer's disease degree scoring, self-care ability score, osteoporosis degree (T value), and combined medical diseases between the two groups ( P>0.05). The operation time, intraoperative blood loss, number of blood transfusions, transfusion volume, length of hospital stay, occurrence of complications, weight-bearing time after operation, and postoperative visual analogue scale (VAS) score, walking ability score, mobility score, self-care ability score were recorded and compared between the two groups. And the radiographic assessment of fracture reduction quality and postoperative stability, and fracture healing time were recorded.@*RESULTS@#The operations in both groups were successfully completed. All patients were followed up 6-15 months with an average time of 9.8 months in PFBN group and 9.6 months in PFNA group. The operation time was significantly longer in PFBN group than in PFNA group ( P<0.05), but there was no significant difference in intraoperative blood loss, number of blood transfusions, transfusion volume, length of hospital stay, change in activity ability score, and change in self-care ability score between the two groups ( P>0.05). The weight-bearing time after operation was significantly shorter in PFBN group than in PFNA group ( P<0.05), and the postoperative VAS score and walking ability score were significantly better in PFBN group than in PFNA group ( P<0.05). Radiographic assessment showed no significant difference in fracture reduction scores and postoperative stability scores between the two groups ( P>0.05). All fractures healed and there was no significant difference in fracture healing time between the two groups ( P>0.05). The incidence of complications was significantly lower in PFBN group (16.7%, 4/24) than in PFNA group (45.8%, 11/24) ( P<0.05).@*CONCLUSION@#Compared with PFNA, PFBN in the treatment of elderly intertrochanteric fractures can effectively relieve postoperative pain, shorten bed time, reduce the risk of complications, and facilitate the recovery of patients' hip joint function and walking ability.

Hyperactivation of PI3K/AKT/mTOR signal pathway impairs TNF-α-induced autophagy in mesenchymal stem cells from patients with ankylosing spondylitis / 南方医科大学学报

OBJECTIVE@#To investigate the changes in autophagy of mesenchymal stem cells (MSCs) from patients with ankylosing spondylitis and explore the mechanism for decreased autophagy in ASMSCs.@*METHODS@#MSCs collected from 14 patients with AS (ASMSCs) and from 15 healthy donors (HDMSCs) were cultured in the absence or presence of 25 ng/mL TNF-α for 6 h. Autophagy of the cells was determined by immunofluorescence staining of GFP-LC3B, and the results were confirmed by detecting the protein expressions of autophagy markers LC3 II/LC3 I and P62. The mRNA expressions of the related genes were detected using qRT-PCR, and the protein expressions of the autophagy markers and signaling pathway-related molecules were determined with Western blotting. TG100713 was used to block the PI3K/AKT/mTOR signal pathway, and its effect on autophagy of ASMSCs was evaluated.@*RESULTS@#ASMSCs showed significantly weaker GFP-LC3B puncta staining and lower protein expression levels of LC3 II/LC3 I but higher levels of P62 protein (P < 0.05), indicating a decreased autophagy capacity as compared with HDMSCs. TNF-α-induced ASMSCs showed significantly higher protein expressions of p-PI3K/ PI3K, p-AKT/AKT and p-mTOR/mTOR than HDMSCs (P < 0.05), suggesting hyperactivation of the PI3K/AKT/mTOR signaling pathway in ASMSCs. Blocking PI3K/AKT/mTOR signaling with TG100713 eliminated the difference in TNF-α-induced autophagy between HDMSCs and ASMSCs.@*CONCLUSION@#In patients with AS, hyperactivation of the PI3K/AKT/mTOR signaling pathway results in decreased autophagy of the MSCs and potentially contributes to chronic inflammation.

Anesthesia management of advanced gallbladder cancer with ultrasound-guided radioactive 125I particle implantation: a case report / 中华内分泌外科杂志

Ultrasound-guided radioactive 125I particle implantation for the treatment of advanced gallbladder cancer is susceptible to factors such as ribs, respiratory activity, and biliary reflex, which brings great inconvenience to the operation. We reported one case of gallbladder cancer patients with unclear ultrasound imaging under general anesthesia mechanical ventilation and successful transplantation after sustained inflation with general anesthesia in order to providing basis of clinical diagnosis and treatment.

Role of TRPV1/NF-κB signaling pathway in dexmedetomidine-induced alleviation of VILI in rats / 中华麻醉学杂志

Objective:To evaluate the role of transient receptor potential vanilloid receptor 1 (TRPV1)/nuclear factor-κB (NF-κB) signaling pathway in dexmedetomidine-induced alleviation of ventilator-induced lung injury (VILI) in rats.Methods:One hundred clean-grade healthy male Sprague-Dawley rats, weighing 270-320 g, aged 4-5 months, were divided into 5 groups ( n=20 each) using a random number table method: control group (group C), VILI group (group V), AMG9810 group (group A), dexmedetomidine group (group D), and dexmedetomidine + RTX group (group DR). VILI model was prepared by mechanical ventilation with a tidal volume of 40 ml/kg for 4 h. In group A, TRPV1 inhibitor AMG9810 30 mg/kg was intraperitoneally injected at 1 h before mechanical ventilation.Dexmedetomidine 5.0 μg/kg was intravenously infused at 20 min before mechanical ventilation, and dexmedetomidine was intravenously infused at the rate of 5.0 μ g·kg -1·h -1 during ventilation in group D and group DR.In group DR, RTX 70 μ g/kg was intraperitoneally injected for 3 consecutive days before mechanical ventilation.At 4 h of mechanical ventilation, the concentrations of interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and IL-6 in bronchoalveolar lavage fluid (BALF) were detected, oxygenation index (OI) and wet/dry lung weight (W/D) ratio were measured, the histopathological changes of lung tissues were observed, and lung injury was assessed and scored.The expression of TRPV1 and NF-κB in lung tissues was detected by Western blot, and real-time polymerase chain reaction was used to detect the expression of TRPV1 and NF-κB mRNA. Results:Compared with group C, the concentrations of IL-1β, TNF-α and IL-6 in BALF were significantly increased, OI was decreased, the W/D ratio and lung injury scores were increased, and the expression of TRPV1 and NF-κB protein and mRNA was up-regulated in group V ( P<0.05). Compared with group V, the concentrations of IL-1β, TNF-α and IL-6 in BALF were significantly decreased, OI was increased, the W/D ratio and lung injury scores were decreased, and the expression of TRPV1 and NF-κB protein and mRNA was down-regulated in A, D and DR groups ( P<0.05). Compared with group D, the concentrations of IL-1β, TNF-α and IL-6 in BALF were significantly increased, OI was decreased, the W/D ratio and lung injury scores were increased, and the expression of TRPV1 and NF-κB protein and mRNA was up-regulated in group DR ( P<0.05). Conclusions:The mechanism by which dexmedetomidine alleviates VILI is partially related to inhibition of the activation of TRPV1/NF-κB signaling pathway and inhibition of the inflammatory responses in lung tissues of rats.

Transform routine medical accelerators to achieve Flash-RT and physical performance measurements / 中华放射肿瘤学杂志

Objective:To investigate the feasibility of transforming conventional medical accelerator to achieve ultra-high dose rate required to achieve Flash radiotherapy (Flash-RT), and to understand the physical properties of the Flash-RT beam.Methods:By transforming the Varian 23CX medical accelerator, the radiation average dose rate at the isocenter was not less than 40 Gy/s. The relevant physical measurement scheme was designed to accurately measure the actual radiation dose rate of different source skin distance (SSD) conditions, the percent depth dose (PDD) curve and the off-axis dose distribution of the beam.Results:The average dose rate of 9 MeV electron beam after the transformation was measured using the HD-V2 type film, the average dose rate of 3 s was 97.9 Gy/s, and the average dose rate of 6 s was 99.27 Gy/s. When the SSD was 100 cm, 80 cm and 60 cm, the average dose rate of 9 MeV electron beam after the transformation was 99.3 Gy/s, 168 Gy/s and 297.5 Gy/s, respectively. After the transformation, the R100 of the 9 MeV beam was 2.2 cm underwater, R50 was 3.87 cm underwater, the electron range Rp was 4.58 cm, and the maximum possible energy Ep,0 on the phantom surface was 9.28 MeV. These parameters were slightly higher than those of the conventional 9 MeV beam, manifested with slight increase in the surface dose and widening high dose flat area. The overall deposit dose distribution exhibited the highest central axis and the increase in dose declines from the axis distance. Under the condition that the field size was 20 cm×20 cm and the SSD was 100 cm, the FWHM of the vertical and horizontal off-axis dose distribution curves were 16.6 cm and 16.4 cm, respectively. Conclusion:By transforming conventional medical accelerator, the average dose rate of the beam at the isocycle meets the requirement of Flash-RT, and the average dose rate under the condition of 60 cm SSD is much higher than the requirement of at least 40 Gy/s for Flash-RT.

Research on cost-benefit analysis of in-hospital falls: based on real world data / 中国实用护理杂志

Objective:Based on the real-world clinical data of hospital electronic medical records, to analyze the length of stay and healthcare costs associated with in-hospital falls and fall injuries in hospitals.Methods:Based on the electronic medical record system of the First Affiliated Hospital of Nanjing Medical University, a retrospective cohort study was conducted on patients admitted to these departments reported falls in nursing management information system from January 2017 to December 2019. A total of 38 481 patients from 74 units were enrolled in this study. The patients′ characteristics, falls, falls injury, and explore the length of hospital stay and bottom-up direct cost were analyzed.Results:A total of 243 cases (0.6%) fell and 154 cases (63.4%) were injured by falls from January 2017 to December 2019. Compared with non-fallers, the median length of stay of patients with falls was 19 days, which was significantly increased compared with 7 days of patients without falls ( Z=-15.18, P<0.05). The median hospitalization cost of patients with falls was 39 000 yuan, which was significantly higher than 16 300 yuan of patients without falls ( Z=-11.47, P<0.01). There was no statistical difference between non-injuried fallers and injuried fallers for length of stay and healthcare costs ( Z=-0.92, -0.64, P>0.05). Linear regression model analysis showed that gender, age, comorbidity, inpatient department unit, reason of hospitalization were significantly correlated with inpatient cost and length of stay ( F=280.05, 217.31, all P<0.05). Conclusions:Patients who have an in-hospital fall have significantly longer hospital stays and higher direct costs, mainly can be attributed to the fall itself, not the injury. Our findings have important financial implications for real world in light of optimal intervention strategies, resource allocation and economic evaluation of fall prevention.

Correlation between serum VEGF level and clinical symptoms in patients with first-episode drug-naive schizophrenia of different genders / 中华行为医学与脑科学杂志

Objective:To investigate the level of serum vascular endothelial growth factor (VEGF) and its correlation with clinical symptoms in patients with first-episode drug-naive schizophrenia patients of different genders.Methods:From January 2016 to October 2019, a total of 81 first-episode drug-naive schizophrenia patients(patient group, 41 male, 40 female) and 64 healthy controls (control group, 40 male, 24 female) were included in this study.The serum level of VEGF was detected with flow cytometric bear array (CBA). Positive and negative symptom scale (PANSS) was used to evaluate the relevant clinical symptoms of patients.SPSS 22.0 software was used for statistical analysis.Independent sample t-test and nonparametric test were used for comparison between groups.The relationship between VEGF and clinical variables was analyzed by Pearson correlation analysis and Spearman correlation analysis. Results:The level of serum VEGF in the patient group was significantly lower than that in the control group(148.08(75.89, 208.61)pg/mL, 179.94(99.14, 318.41)pg/mL, Z=-2.20, P=0.028). The total PANSS score((82.71±17.30), (73.45±16.36), t=2.473, P=0.016)and cognitive score((7.88±3.36), (6.23±2.81), t=2.402, P=0.019) in male patients were higher than those in female patients.There was a negative correlation between VEGF level and PANSS negative symptom score in the patient group( r=-0.228, P=0.041), as well as significant negtive correlation between VEGF level and cognitive score in male patients( r=-0.425, P=0.007). Conclusion:The level of serum VEGF is reduced in first-episode patients with schizophrenia, which influences their negative symptom. Moreover, the decline in serum VEGF level is implicated in cognitive impairments in male patients with first-episode schizophrenia.