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.

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.

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.

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.

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.

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.

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）］

Evaluation of the treatment of functional dyspepsia of deficiency cold of spleen and stomach by He Style fire acupuncture / 国际中医中药杂志

Objective:To observe the curative effect of He Style fire acupuncture on functional dyspepsia of deficiency cold of spleen and stomach syndrome.Methods:Sixty patients who met the inclusion criteria from March 2017 to March 2019 in Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University were divided into 2 groups according to the random number table method, with 30 in each group. The control group was given mosapride tablets, one tablet (5 mg) each time half an hour before meals. On the basis of the control group, the treatment group was given fire acupuncture on Zusanli(ST36), Zhongwan(CV12), Pishu(BL20), Weishu(BL21), Guanyuan(CV4) and Qihai (CV6) twice a week. The course of treatment for both groups of patients was 4 weeks. A follow-up was visited at 1 month after the treatment. The total Symptom Scores and Health-Related Quality of Life Scale (SF-36) scores were performed before and after treatment, and the total scores of syndromes of patients with Deficiency cold of spleen and stomach before and after treatment were used for clinical efficacy evaluation, and adverse events during treatment were recorded.Results:The total efficiency of the treatment group was 93.3% (28/30), and 76.7% (23/30) in the control group, and the 2 groups were statistically significant ( χ2=4.78, P<0.05). After treatment, the upper abdominal pain, upper abdominal burning, postprandial fullness and discomfort, early satiety, and total scores in the treatment group were significantly lower than those in the control group ( t values were 4.27, 5.16, 3.93, 4.69, 4.28, respectively, all Ps<0.05); during follow-up, the upper abdominal pain, upper abdominal burning, postprandial fullness and discomfort and the total scores in the treatment group were significantly lower than those in the control group ( t values were 3.63, 3.22, 4.03, 3.04, respectively, all Ps<0.05). In terms of SF-36, after treatment, the treatment group showed significantly higher scores in the control group of physical function, physiology, mental health, and health changes compared with the control group ( t values were 2.97, 4.05, 4.22, 3.05, respectively, all Ps<0.05). During follow-up, the treatment group with physiological function, physical function, physical pain, overall health, life vitality, mental health, health changes scores were significantly higher than those in the control group ( t values were 3.27, 4.23 3.85, 3.15, 3.25, 6.15, 3.85, respectively, all Ps<0.05). Conclusion:He Style fire acupuncture combined with western medicine treatment can improve the symptoms of upper abdominal pain and upper abdominal burning, and the quality of lifein the patients with functional dyspepsia.

The gut microbial metabolite, 3,4-dihydroxyphenylpropionic acid, alleviates hepatic ischemia/reperfusion injury via mitigation of macrophage pro-inflammatory activity in mice

Hepatic ischemia/reperfusion injury (HIRI) is a serious complication that occurs following shock and/or liver surgery. Gut microbiota and their metabolites are key upstream modulators of development of liver injury. Herein, we investigated the potential contribution of gut microbes to HIRI. Ischemia/reperfusion surgery was performed to establish a murine model of HIRI. 16S rRNA gene sequencing and metabolomics were used for microbial analysis. Transcriptomics and proteomics analysis were employed to study the host cell responses. Our results establish HIRI was significantly increased when surgery occurred in the evening (ZT12, 20:00) when compared with the morning (ZT0, 08:00); however, antibiotic pretreatment reduced this diurnal variation. The abundance of a microbial metabolite 3,4-dihydroxyphenylpropionic acid was significantly higher in ZT0 when compared with ZT12 in the gut and this compound significantly protected mice against HIRI. Furthermore, 3,4-dihydroxyphenylpropionic acid suppressed the macrophage pro-inflammatory response in vivo and in vitro. This metabolite inhibits histone deacetylase activity by reducing its phosphorylation. Histone deacetylase inhibition suppressed macrophage pro-inflammatory activation and diminished the diurnal variation of HIRI. Our findings revealed a novel protective microbial metabolite against HIRI in mice. The potential underlying mechanism was at least in part, via 3,4-dihydroxyphenylpropionic acid-dependent immune regulation and histone deacetylase (HDAC) inhibition in macrophages.

Luteoloside protects the vascular endothelium against iron overload injury via the ROS/ADMA/DDAH II/eNOS/NO pathway / 中国天然药物

Iron overload injury is considered to be a part of blood stasis syndrome of arthralgia in traditional Chinese medicine. Its primary therapies include clearing heat and detoxification, activating blood circulation, and removing blood stasis. Lonicera japonica flos (LJF) has long been known as an excellent antipyretic and antidote. Luteoloside (Lut) is one of the main components of LJF and exhibits antioxidant, anti-inflammatory, and cytoprotective properties. However, the protection of Lut against iron overload injury and its underlying mechanisms remain unclear. Therefore, HUVECs were exposed to 50 μmol·L-1 iron dextran for 48 h to establish an iron overload damage model and the effects of Lut were assessed. Our results showed that 20 μmol·L-1 Lut not only increased cell viability and weakened LDH activity, but also significantly up-regulated DDAHⅡ expression and activity, increased p-eNOS/eNOS ratio and NO content, and reduced ADMA content in HUVECs exposed to iron overload. Furthermore, Lut significantly attenuated intracellular/mitochondrial ROS generation, improved SOD, CAT, and GSH-Px activities, reduced MDA content, maintained MMP, inhibited mPTP opening, prevented cyt c from mitochondria released into cytoplasm, reduced cleaved-caspase3 expression, and ultimately decreased cell apoptosis induced by iron overload. The effects of Lut were similar to those of L-arginine (an ADMA competitive substrate), cyclosporin A (a mPTP blocker agent), and edaravone (a free radical scavenger) as positive controls. However, addition of pAD/DDAH II-shRNA adenovirus reversed the above beneficial effects of Lut. In conclusion, Lut can protect HUVECs against iron overload injury via the ROS/ADMA/DDAH II/eNOS/NO pathway. The mitochondria are the target organelles of Lut's protective effects.

Mechanism of emodin in relieving neuropathic pain by regulating serum metabolism / 中国中药杂志

The present study investigated the effect of emodin on the serum metabolite profiles in the chronic constriction injury(CCI) model by non-target metabolomics and explored its analgesic mechanism. Twenty-four Sprague Dawley(SD) rats were randomly divided into a sham group(S), a CCI group(C), and an emodin group(E). The rats in the emodin group were taken emodin via gavage once a day for fifteen days(50 mg·kg~(-1)) on the first day after the CCI surgery. Mechanical withdrawal threshold(MWT) and thermal withdrawal threshold(TWL) in each group were performed before the CCI surgery and 3,7, 11, and 15 days after surgery. After 15 days, blood samples were collected from the abdominal aorta. The differential metabolites were screened out by non-target metabolomics and analyzed with Kyoto Encyclopedia of Genes and Genomes(KEGG) and ingenuity pathway analysis(IPA). From the third day after CCI surgery, the MWT and TWL values were reduced significantly in both CCI group and emodin group, compared with the sham group(P<0.01). At 15 days post-surgery, the MWT and TWL values in emodin group increased significantly compared with the CCI group(P<0.05). As revealed by non-target metabolomics, 72 differential serum metabolites were screened out from the C-S comparison, including 41 up-regulated and 31 down-regulated ones, while 26 differential serum metabolites from E-C comparison, including 10 up-regulated and 16 down-regulated ones. KEGG analysis showed that the differential metabolites in E-C comparison were enriched in the signaling pathways, such as sphingolipid metabolism, arginine biosynthesis, glycerophospholipid metabolism, and tryptophan metabolism. IPA showed that the differential metabolites were mainly involved in the lipid metabolism-molecular transport-small molecule biochemistry network. In conclusion, emodin can exert an analgesic role via regulating sphingolipid metabolism and arginine biosynthesis.

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.

Meta-analysis of acupuncture and moxibustion for the therapeutic effect on postoperative gastrointestinal dysfunction of gastric cancer / 中国针灸

OBJECTIVE@#To systematically review the therapeutic effect of acupuncture and moxibustion on postoperative gastrointestinal dysfunction (GID) of gastric cancer with meta-analysis.@*METHODS@#The articles of randomized controlled trials (RCTs) of acupuncture and moxibustion treatment for postoperative GID of gastric cancer were retrieved from the following databases from the time of database establishment to December 31, 2020, including PubMed, EMbase, Cochrane Central Register of Controlled Trials (CENTRAL), China National Knowledge Infrastructure (CNKI), Wanfang database, VIP database and China Biomedical Literature Database (SinoMed). RevMan5.3 software was used for meta-analysis. Using Stata16.0 software, sensitivity analysis and publication bias test were performed.@*RESULTS@#A total of 16 RCTs were included finally, including 1 360 patients, of which, there were 681 cases in the intervention group and 679 cases in the control group. Meta-analysis results showed that acupuncture and moxibustion shortened the time of first flatus (P<0.000 01, MD =-14.52, 95%CI = [-17.31, -11.74]), the time of first bowel sound (P<0.000 01, MD =-10.50, 95%CI =[-13.99, -7.01]) and the time of first defecation (P<0.000 1, MD =-13.79, 95%CI =[-20.09, -7.50]). Meanwhile, acupuncture and moxibustion shortened the time of the first food intake (P<0.000 1, MD =-3.23, 95%CI = [-3.45, -3.00]) and the hospital stay (P<0.000 01, MD =-1.94, 95%CI =[-2.20, -1.69]) after gastric cancer operation, and reduced the incidences of postoperative adverse reactions, i.e. nausea and vomiting (P =0.000 3, RR =0.43, 95%CI =[0.28, 0.68]) and abdominal distention (P =0.000 5, RR =0.41, 95%CI =[0.25, 0.68]).@*CONCLUSION@#Acupuncture and moxibustion can promote the recovery of postoperative gastrointestinal function in the patients with gastric cancer. But, for the comparison among different measures of acupuncture and moxibustion intervention, it needs more high-quality trials for a further verification.