Objective To analyze the change in levels of high mobility group box 1 protein (HMGB1), interleukin-32 (IL-32), matrix metalloproteinase-9 (MMP-9)/tissue inhibitor of metalloproteinase-1 (TIMP-1) in peripheral blood of patients with lupus nephritis (LN) and their values in predicting prognosis. Methods A total of 86 patients with LN from October 2021 to June 2023 were selected and treated with induction therapy for 6 months. Based on remission status of the disease, patients were divided into remission group (n=66) and non-responder group (n=20). Baseline data, change in levels and reduction rates of HMGB1, IL-32 and MMP-9/TIMP-1, and the partial correlation of reduction rates of HMGB1, IL-32 and MMP-9/TIMP-1 levels in peripheral blood with treatment response as well as their predictive values for treatment response were compared between the two groups. Disease progression was compared between patients with different reduction rates of HMGB1, IL-32 and MMP-9/TIMP-1. Results HMGB1, IL-32 and MMP-9/TIMP-1 levels in the remission group decreased significantly at 1 and 3 months after treatment compared to before treatment (P < 0.05); the levels of HMGB1, IL-32 and MMP-9/TIMP-1 in the remission group were significantly lower than those in the non-responder group at 1 and 3 months after treatment (P < 0.05); the reduction rates of HMGB1, IL-32 and MMP-9/TIMP-1 levels in the remission group were significantly higher than those in the non-responder group at 1 and 3 months after treatment (P < 0.05). Partial correlation analysis showed that the reduction rates of HMGB1, IL-32 and MMP-9/TIMP-1 levels were independently significantly correlated with treatment response (P < 0.05). One and three months after treatment, the values of the area under the curve (AUC) for the combined prediction of remission by the reduction rates of HMGB1, IL-32 and MMP-9/TIMP-1 levels were 0.910 and 0.932 respectively, with the AUC being the largest at 3 months after treatment (P < 0.05). Patients were divided into high and low reduction rate subgroups based on theoptimal cut-off value from the ROC curve analysis at 3 months after treatment, and the disease progression rate was significantly lower in the high reduction rate subgroup than in the low reduction rate subgroup for HMGB1, IL-32 and MMP-9/TIMP-1 (P < 0.05). Conclusion The great change in levels of HMGB1, IL-32 and MMP-9/TIMP-1 in peripheral blood of LN patients is significantly correlated with treatment response and disease progression, and the combined detections of HMGB1, IL-32 and MMP-9/TIMP-1 levels at 1 and 3 months after treatment have high value in predicting the treatment response of LN patients.

Objective To explore the difference in gut microbiota composition between patients with obstructive sleep apnea(OSA)and healthy individuals and the role of gut microbiota in the pathogenesis of OSA.Methods Thirty-nine patients with OSA admitted to our hospital between May and December,2022 and 20 healthy individuals were enrolled in this study.Stool samples were collected from all the participants for analysis of microbiome composition using 16S rRNA high-throughput sequencing analysis.The alpha diversity,beta diversity,and species difference were determined between the two groups and marker species analysis and metabolic pathway function prediction analysis were performed.Results The species diversity(Shannon and Simpson)indexes,richness(observed species)and evenness(Pielou)of gut microbiota were significantly lower in OSA patients than in the healthy individuals(P<0.05).The OSA patients had also a significantly lowered community diversity(P<0.05)with different gut microbial communities from those of the healthy individuals shown by increased relative abundance of potentially pathogenic bacteria such as Pseudomonas and Monocytogenes(P<0.05).LEfSe analysis showed that the abundance of 23 species of gut microbiota differed significantly between the two groups and the OSA patients had significant increases in the abundance of Pseudomonas,Meganomonas,and Fusobacterium(P<0.05).The differential marker flora affected host homeostasis.Random Forest and ROC curve analyses confirmed that Pseudomonas could be used as important biomarkers for a differential diagnosis.Metabolic pathway function prediction analysis showed that biosynthesis function had the greatest contribution to maintaining gut microbiota homeostasis,and Pseudomonas affected the occurrence and progression of OSA by participating in aromatic bioamine degradation and ketogluconic acid metabolic pathway.Conclusion OSA patients have obvious gut microbiota disturbances,and Pseudomonas may affect the development of OSA by participating in substance metabolism to serve as the potential target gut bacteria for OSA treatment.

Objective To explore the difference in gut microbiota composition between patients with obstructive sleep apnea(OSA)and healthy individuals and the role of gut microbiota in the pathogenesis of OSA.Methods Thirty-nine patients with OSA admitted to our hospital between May and December,2022 and 20 healthy individuals were enrolled in this study.Stool samples were collected from all the participants for analysis of microbiome composition using 16S rRNA high-throughput sequencing analysis.The alpha diversity,beta diversity,and species difference were determined between the two groups and marker species analysis and metabolic pathway function prediction analysis were performed.Results The species diversity(Shannon and Simpson)indexes,richness(observed species)and evenness(Pielou)of gut microbiota were significantly lower in OSA patients than in the healthy individuals(P<0.05).The OSA patients had also a significantly lowered community diversity(P<0.05)with different gut microbial communities from those of the healthy individuals shown by increased relative abundance of potentially pathogenic bacteria such as Pseudomonas and Monocytogenes(P<0.05).LEfSe analysis showed that the abundance of 23 species of gut microbiota differed significantly between the two groups and the OSA patients had significant increases in the abundance of Pseudomonas,Meganomonas,and Fusobacterium(P<0.05).The differential marker flora affected host homeostasis.Random Forest and ROC curve analyses confirmed that Pseudomonas could be used as important biomarkers for a differential diagnosis.Metabolic pathway function prediction analysis showed that biosynthesis function had the greatest contribution to maintaining gut microbiota homeostasis,and Pseudomonas affected the occurrence and progression of OSA by participating in aromatic bioamine degradation and ketogluconic acid metabolic pathway.Conclusion OSA patients have obvious gut microbiota disturbances,and Pseudomonas may affect the development of OSA by participating in substance metabolism to serve as the potential target gut bacteria for OSA treatment.

Objective To study the pathological features of argyrophilic grains in normal aging brain, AD, PD and progressive superior nuclear paralysis patients. Methods Brain tissue samples taken from 5 AD, 3 PD, 2 progressive superior nuclear paralysis patients with complete clinico-pathological data and 4 normal aging brain subjects were stained with HE, Luxol fast blue and Gallyas-Braak silver respectively. Aβ, tau, α-synuclein and P62 antibodies were detected by microscopy with immunohistochemical staining. The pathological features of argyrophilic grains were recorded. Results The Gallyas-Braak silver staining showed argyrophilic grain structure in 4 out of the 14 amygdaloid nucleus tissue samples (2 from AD patients, 1 from progressive superior nuclear paralysis patients and 1 from normal aging brain patients) with a positive rate of 28.6％. The immunohistochemical staining showed positive tau and P62 antibodies. Conclusion Argyrophilic grain lesion is not uncommon in aging-related neurodegenerative diseases such as normal aging brain, AD and progressive superior nuclear paralysis and can thus produce its superposition effect on the clinical symptoms of cognitive impairment in AD and progressive superior nuclear paralysis patients.

Objective To promote the Institutional Review Board(IRB) construction and development via paying more attention to the detail management and providing better protection of subjects' rights and interests in ethical review of clinical trials and scientific research projects.Methods Assessment criteria were established according to the domestic and international laws and regulations on the management of ethical and scientific research project.Ethical site visit was performed on the 37 clinical trials/scientific research projects approved by IRB during the year 2012-2015.Results Clinical trials/scientific research projects were divided into tree types:the registered clinical trials,the post-marketing clinical trials and the researcher initiated scientific research project.All the types met with the following assessment criteria:satisfy the requirement of equipment,facilities and qualifications of drug preservation required for conducting clinical research;subjects were given compensation according to the protocol;informed consent were obtained.Among them,the registered clinical trials meet more criteria than other research types.Regarding to the standard of informed consent implementation,all types met with the following assessment criteria:all the subjects enrolled signed informed consent forms,informed consent forms are well documented;investigators and subjects/ the guardian signed the forms.However,during the site visit,some other criteria were also neglected more or less.Particularly,only few project recorded the consent process and time spots singed the forms.Conclusions Investigators should pay more attention to the activities and behaviors taken place during the research implementation process.Researchers and management staffs should pay attention to ethical detail management to guarantee better protection of subjects' rights and interests.

Objective To explore the application and significance of intraoperative laparoscopic ultrasound( IOUS) in robot-assisted laparoscopic hepatectomy . Methods From February 2015 to February 2017 ,135 patients undergoing liver resection with robotic approach were enrolled in the study . All data about demographic ,surgical procedure and postoperative course were collected prospectively and analyzed . IOUS was routinely performed in these patients . To assist the localization and resection of liver tumor ,a four steps IOUS protocol in robotic liver surgery was proposed ,including exploration ,verification ,guidance , and confirmation . If necessary ,intraoperative laparoscopic ultrasound guided microwave ablation of liver tumor to complete the treatment . Results A total of 11 additional lesions in 11 patients were detected in 135 patients ,7 patients accepted strategic surgical modification : 4 cases were enlarged resection ,and 3 cases were treated with microwave ablation . There were only 17 patients lost blood more than 1000 ml in all patients . No patient suffered from any single or multiple organ dysfunctions ,and there was no mortality observed . Conclusions IOUS is indispensable to understand lesions and vessels ,confirm the complete resection of the tumor in robot-assisted laparoscopic hepatectomy . It is also a necessary tool for the microwave ablation of liver tumor .

A new caffeate compound, (E)-erythro-syringylglyceryl caffeate (1), was isolated from the roots and rhizomes of Nardostachys chinensis Batal., together with nine known phenolic compounds, including (+)-licarin A (2), naringenin 4', 7-dimethyl ether (3), pinoresinol-4-O-β-D-glucoside (4), caraphenol A (5), Z-miyabenol C (6), protocatechuic acid (7), caffeic acid (8), gallic acid (9) and vanillic acid (10). Their chemical structures were elucidated on the basis of spectroscopic data and physicochemical properties. Furthermore, this is the first report of compounds 2, 5 and 6 from Nardostachys genus.

AIM:To investigate the effect of microRNA-214 ( miR-214) on cardiomyocyte hypertrophy and the expression of the potential target genes .METHODS:A cell model of hypertrophy was established based on angiotensin-Ⅱ( Ang-Ⅱ)-induced neonatal mouse ventricular cardiomyocytes ( NMVCs) .Dual luciferase reporter assay was performed to verify the interaction between miR-214 and the 3’ UTR of MEF2C.The expression of MEF2C and hypertrophy-related genes at mRNA and protein levels was determined by RT-qPCR and Western blot , respectively .RESULTS:The expression of ANP, ACTA1,β-MHC and miR-214 was markedly increased in Ang-Ⅱ-induced hypertrophic cardiomyocytes .Dual lu-ciferase reporter assay revealed that miR-214 interacted with the 3’ UTR of MEF2C, and miR-214 was verified to inhibit MEF2C expression at the transcriptional level .The protein expression of MEF2C was markedly increased in the hypertro-phic cardiomyocytes .Moreover, miR-214 mimic, in parallel to MEF2C siRNA, inhibited the expression of hypertrophy-re-lated genes in Ang-Ⅱ-induced NMVCs.CONCLUSION:MEF2C is a target gene of miR-214, which mediates the effect of miR-214 on attenuating cardiomyocyte hypertrophy .

OBJECTIVETo investigate histopathology and proteinopathy in the spinal cord of patients with common neurodegenerative diseases.

METHODSSpinal cord tissues from clinically and neuropathologically confirmed neruodegnerative diseases were enrolled in this study, including 3 cases of multiple system strophy, 4 cases of amyotrophic lateral sclerosis, 5 cases of Alzheimer's disease (AD, included 2 cases of AD combined with Parkinson's disease), 2 cases of progressive supranuclear palsy, 1 case of dementia with lewy body and 1 case of corticobasal degeneration from 1955 to 2013 at Chinese People's Liberation Army General Hospital. Four normal control cases were also included. Routine HE and Gallyas-Braak staining, and immunohistochemical stainings for anti-PHF tau (AT8), anti-α-synuclein, anti-TDP-43 and anti-ubiquitin were performed.

RESULTSExamination of the spinal cord in 3 cases with multiple system strophy revealed severe neuron loss in the intermediolateral nucleus of thoracic segment and Onuf's nucleus of the sacral segment, along with moderate neuron loss in the anterior horn of the cervical segment and mild myelin pallor in the anterior funiculus and anterolateral funiculus in the cervical and thoracic segments. Large amount of argentophilic, ubiquitin and synuclein positive oligodendroglial cytoplasmic inclusions were found widely distributed in the anterior horn and the anterior funiculus and anterolateral funiculus of the full spinal cord. Severe neuron loss and several morphological changes with gliosis in the anterior horn and severe loss of myelin in the anterior funiculus and anterolateral funiculus of the full spinal cord were observed in 4 cases of amyotrophic lateral sclerosis, 2 of which were found with Bunina bodies in neurons of the anterior horn. Three amyotrophic lateral sclerosis cases had ubiquitin-positive neuronal inclusions and TDP-43 positive neuronal and glial inclusions in the anterior horn at cervical and lumbar segments. A few argentophilic, tau positive neurofibrillary tangles (NFTs) and neuropil threads in the anterior horn at cervical and lumbar segments were found in 4 AD cases. Examination of spinal cord in 2 cases with Parkinson's disease combined with AD and 1 case with dementia with lewy body revealed severe neuron loss in the intermediolateral nucleus of thoracic segment, and a few synuclein positive lewy bodies and neuritis were also observed. There was mild neuron loss in the anterior horn at cervical and lumbar segments, along with some argentophilic, tau positive globous NFTs and many argentophilic, tau positive neutrophil threads were observed in 2 progressive supranuclear palsy cases and 1 corticobasal degeneration case.

CONCLUSIONEach common neurodegenerative diseases of the spinal cord including multiple system strophy, amyotrophic lateral sclerosis and Parkinson's disease has its own specific histopathology and proteinopathy characteristics.

Alzheimer Disease ; pathology ; Amyotrophic Lateral Sclerosis ; pathology ; DNA-Binding Proteins ; metabolism ; Humans ; Immunohistochemistry ; Inclusion Bodies ; pathology ; Neurodegenerative Diseases ; pathology ; Neurofibrillary Tangles ; pathology ; Neurons ; pathology ; Parkinson Disease ; pathology ; Spinal Cord ; pathology ; Ubiquitin ; metabolism ; alpha-Synuclein ; metabolism